Effects of Lipopharyngeal Qibi Formula on swallowing function and apoptosis in central cortical swallowing neurons in rats after stroke / 中国组织工程研究

BACKGROUND:The treatment of post-stroke dysphagia with Lipopharyngeal Qibi Formula has achieved good efficacy,and 5-hydroxytryptamine in peripheral serum and neurotransmitters in the nucleus tractus solitarius are closely related to swallowing.Therefore,this study was conducted to explore the modulatory effects of peripheral serum and nucleus tractus solitarius neurotransmitters in swallowing by using modern medical experimental methods such as molecular biology,thereby developing new ideas for the exploration of their mechanisms. OBJECTIVE:To verify the therapeutic effect of Lipopharyngeal Qibi Formula on post-stroke dysphagia and to investigate its mechanism of action. METHODS:Thirty-eight Sprague-Dawley rats were randomly divided into model group(n=14),treatment group(n=14)and sham-operated group(n=10).Animals in the model and treatment groups were modeled by reperfusion after 90 minutes of transient cerebral ischemia by wire bolus method.At 6 hours after modeling,neurological function was scored,and rats with a score of 2 were selected for subsequent experiments.The treatment group was given compound Lipopharyngeal Qibi Formula by gavage starting from the 2nd day after modeling and the remaining two groups were given normal saline by gavage.Changes in body mass,24-hour food and water intake were recorded on days 2,7,14 and 30.The swallowing initiation response time and the number of swallows were detected using a biosignal collector and a tonic transducer on days 14 and 30.After the swallowing test,the ischemic area of the brain in each group was measured by TTC staining.The expression of 5-hydroxytryptamine in the nucleus tractus solitarius of the medulla oblongata was measured by immunohistochemistry.The mRNA and protein expression levels of BCL-2 and BAX in the insula,premotor cortex,cingulate cortex and thalamus of rats in each group were measured by RT-PCR and Western blot,respectively. RESULTS AND CONCLUSION:Compared with the sham-operated group,the body mass,24-hour food intake and water intake were reduced,the swallow initiation response time was prolonged,and the number of swallows was reduced in the treatment and model groups at day 14 of gavage(P＜0.05).Compared with the model group,the body mass,24-hour food intake and water intake of rats were increased in the treatment group at day 30 of gavage(P＜0.05),but were still lower than those in the sham-operated group.Compared with the model group,the swallow initiation reaction time was shortened and the number of swallows increased in the treatment group,but the number of swallows was still significantly lower than that in the sham-operated group(P＜0.05).Cerebral ischemia area was reduced in the treatment group compared with the model group,and the number of 5-hydroxytryptamine-positive cells in the nucleus tractus solitarius of the medulla oblongata was increased in the treatment group compared with the model group,but it was still significantly lower than that in the sham-operated group(P＜0.05).Compared with the model group,the expression of BCL-2 mRNA and protein in the insula,cingulate cortex and thalamus of rats in the treatment group were significantly increased,the expression of BAX mRNA and protein were significantly decreased,and the BCL-2/BAX ratio was significantly increased(P＜0.05).To conclude,the Chinese herbal compound Lipopharyngeal Qibi Formula could improve the number of swallows and swallowing initiation response time,as well as 24-hour food intake,body mass and other swallowing-related indexes in rats with post-stroke dysphagia.The mechanism of action may be achieved by improving the area of cerebral ischemia,inhibiting the apoptosis of neuronal cells in the insula,cingulate cortex and thalamus of rats,thus improving the regulation of the higher centers on the medulla oblongata swallowing center,and regulating the level of 5-hydroxytryptamine in the nucleus tractus solitarius.

Evaluation of dual-parameter 3D-ASL on blood-supply of patients with CMCAO and the relationship between that and cerebral infarction area / 中国医学装备

Objective:To explore the evaluation of dual-parameter three dimension arterial spin labelling(3D-ASL)perfusion imaging on blood-supply situation of patients with chronic middle cerebral artery occlusion(CMCAO)and the relationship between that and cerebral infarction area.Methods:A total of 112 patients with unilateral CMCAO admitted to Handan Central Hospital from April 2019 to December 2021 were selected,and all of them were divided into a compensatory group(50 cases)with anterior cerebral artery(ACA)leptomeningeal anastomoses(LMA)and an uncompensated group(62 cases)according to the results of digital subtraction angiography(DSA)examination.The results of diffusion weighted imaging(DWI),magnetic resonance angiography(MRA)and dual-parameter 3D-ASL detection were respectively analyzed,and the clinical data,3D-ASL parameters and the incidence of cerebral infarction between the two groups were compared.The influence factors of compensation were further analyzed.The receiver operating characteristics(ROC)curve of LMA diagnostic value of CMCAO patients was drawn according to cerebral blood flow values[post label delay(PLD)=1.5 s,2.5 s)].The 3D-ASL parameters of patients with different cerebral infarction areas were compared,and the relationship between 3D-ASL parameters and cerebral infarction area was compared.Results:The apparent diffusion coefficient(ADC)at the side of lesion of CMCAO patients was(0.31±0.10),and cerebral blood flow values at 1.5s and 2.5s were respectively(25.67±4.25)and(54.09±4.49),which were significantly lower than those at the side of healthy,and the differences were statistically significant(t=27.591,34.210,3.913,P<0.05),respectively.The differences of cerebral blood flow values(1.5s and 2.5s)between compensatory group and uncompensated group were significant(t=5.584,4.090,P<0.05),respectively.The results of logistic regression analysis showed that age,stroke,cerebral infarction area and cerebral blood flow values(1.5 s and 2.5 s)were influencing factors on LMA compensation of CMCAO patients(OR=4.187,6.604,0.482,5.681,5.807,P<0.05),respectively.The ROC values showed that the area under curve(AUC)of 3D-ASL were respectively 0.720 and 0.812 in diagnosing LMA when PLD were respectively 1.5s and 2.5s.The proportion of normal and lacunar infarctions in the compensatory group was significantly higher than that in the uncompensated group,while the proportions of middle and small infarction,and large area infarctions of the compensatory group were significantly lower than those of the uncompensated group,and the difference was statistically significant(t=28.062,P<0.05).The difference in cerebral blood flow values(1.5s)among patients with different infarct areas was statistically significant(t=0.202,P<0.05).The cerebral blood flow value(1.5s)of 3D-ASL was negatively correlated with the area of cerebral infarction(r=-0.261,P<0.05).Conclusion:Dual parameter 3D-ASL can non-invasively and visually assess the compensatory status of LMA of patients with unilateral CMCAO.The blood flow perfusion of middle cerebral artery(MCA)at the side of lesion is related to the area of cerebral infarction.When the PLD is 1.5s,the sensitive response can be conducted on this,so as to provide objective and reliable basis for clinical diagnosis and treatment and curative effect.

Dynamic changes in cytoskeletal elements following acute cerebral ischemia and reperfusion in rats / 中国药理学通报

Aim To investigate the dynamic time-course changes in neuronal cytoskeleton after acute ischemia and reperfusion in rats. Methods Reperfusion was performedin rats by blocking the middle cerebralarteryfor 90 min, then therats wereobserved and collected at different time points. The brain damage wasobserved by Nissl staining,and neurobehavioural function was evaluated with neurological deficit score and forelimb placement test. The cellular changes in the alternations of cytoskeletal elements including microtubule associated protein 2 (MAP2) and neurofilament heavy chain (NF-H) were observed by immunohistochemistry staining and Western blot. Impaired axons, dendrites and cytoskeletal alternations were detected by electron microscope. Results Brain damage and neurobehavioural function were gradually aggravated with the prolongation of reperfusion. Brain damage appeared earlier and more severe in striatum than in cortex. Moreover, decreased MAP2-related and increased NF-H-related immunoreactive intensities were found in the ischemic areas. Impaired cytoskeletal arrangement and reduced dense were indicated. Damaged cytoskeletal components such as microtubules and neurofilament arrangement, decreased axonal filament density, and swelled dendrites were observed after cerebral ischemia reperfusion by ultrastructural observations. Conclusions Different brain regions have diverse tolerance to ischemia-reperfusion injury. Major elements of neuronal cytoskeleton show dynamic responses to ischemia and reperfusion, which may further contribute to brain damage and neurological impairment following MCAO and reperfusion.

Effects of Tao Hong Si Wu decoction on IncRNA expression in rats with occlusion of middle cerebral artery / 中国药理学通报

Aim To screen and study the expression of long non-coding RNA (IncRNA) in rats with middle cerebral artery occlusion (MCAO) with MCAO treated with Tao Hong Si Wu decoction (THSWD) and determine the possible molecular mechanism of THSWD in treating MCAO rats. Methods Three cerebral hemisphere tissue were obtained from the control group, MCAO group and MCAO + THSWD group. RNA sequencing technology was used to identify IncRNA gene expression in the three groups. THSWD-regulated IncRNA genes were identified, and then a THSWD-regu-lated IncRNA-mRNA network was constructed. MCODE plug-in units were used to identify the modules of IncRNA-mRNA networks. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) were used to analyze the enriched biological functions and signaling pathways. Cis- and trans-regulatory genes for THSWD-regulated IncRNAs were identified. Reverse transcription real-time quantitative pol-ymerase chain reaction (RT-qPCR) was used to verify IncRNAs. Molecular docking was used to identify IncRNA-mRNA network targets and pathway-associated proteins. Results In MCAO rats, THSWD regulated a total of 302 IncRNAs. Bioinformatics analysis suggested that some core IncRNAs might play an important role in the treatment of MCAO rats with THSWD, and we further found that THSWD might also treat MCAO rats through multiple pathways such as IncRNA-mRNA network and network-enriched complement and coagulation cascades. The results of molecular docking showed that the active compounds gallic acid and a-mygdalin of THSWD had a certain binding ability to protein targets. Conclusions THSWD can protect the brain injury of MCAO rats through IncRNA, which may provide new insights for the treatment of ischemic stroke with THSWD.

Therapeutic effect of sequential therapy with butylphthalein on acute cerebral infarction and increased middle cerebral artery blood flow in 48 patients / 中国基层医药

Objective:To investigate the therapeutic effect of sequential therapy with butylphthalein on acute cerebral infarction and mild-to-moderate increases in middle cerebral artery blood flow in patients.Methods:The clinical data of 92 patients with acute cerebral infarction and mild-to-moderate increases in middle cerebral artery blood flow who received treatment at the Xiaogan Hospital Affiliated to Wuhan University of Science and Technology from January 2018 to October 2021 were retrospectively analyzed. These patients were divided into a study group and a control group using a random number table method. The control group was given an intravenous infusion of butylphthalein sodium chloride injection, while the study group took oral butylphthalein soft capsules after intravenous infusion of butylphthalein sodium chloride injection. The baseline data, hemodynamics, neurological function, and clinical outcomes were compared between the two groups. At 90 days after treatment, the National Institutes of Health Stroke Scale (NIHSS), the Activity of Daily Living Scale (ADL), and the modified Rankin Scale (mRS) were used to evaluate clinical outcomes. Transcranial Doppler ultrasound (TCD) examination was performed to evaluate hemodynamic changes.Results:A total of 92 patients completed all the observation indices as required, including 48 patients in the study group and 44 patients in the control group. There were no significant differences in demographics, vascular risk factors, laboratory results, NIHSS score, ADL score, or arterial hemodynamics of the diseased brain between the two groups (all P > 0.05). At 90 days after treatment, the NIHSS score in the study group was significantly lower than that in the control group [(4.00 ± 1.95) points vs. (4.91 ± 2.08) points; t =-2.16, P = 0.033]. The ADL score in the study group was significantly higher than that in the control group [(82.71 ± 9.56) points vs. (76.25 ± 11.47) points; t = 2.94, P = 0.004]. The good rate of outcomes in the study group was significantly higher than that in the control group [70.83% (34/48) vs. 50.00% (22/44); χ2 = 4.18, P = 0.041]. There were significant differences in the peak systolic velocity [(152.33 ± 9.58) cm/s vs. (157.41 ± 11.77) cm/s; t = 2.27, P = 0.025] and the mean velocity [(90.00 ± 8.30) cm/s vs. (94.45 ± 9.07) cm/s; t = -2.46, P = 0.016] of the middle cerebral artery between the study and control groups. The difference in pulsitility index between the two groups was not statistically significant [(0.97 ± 1.06) vs. (1.01 ± 1.21); t = 1.69, P = 0.093]. Compared with the poor outcome group, patients in the good outcome group had lower NIHSS and ADL scores after discharge (both P < 0.001), and the proportion of patients who received sequential therapy with butylphthalein in the good outcome group was higher [(60.70% (34/56) vs. 38.90% (14/36); χ2 = 4.18, P = 0.041]. Conclusion:Sequential therapy with butylphthalein can reduce neurological deficits, promote neurological function recovery, improve the hemodynamics of diseased blood vessels, and greatly improve daily living activities in patients with acute cerebral infarction complicated by mild to moderate increases in middle cerebral artery blood flow.

Clinical effect of superficial temporal artery-middle cerebral artery anastomosis in the treatment of occlusive cerebrovascular disease / 局解手术学杂志

Objective To investigate the clinical effect of superficial temporal artery-middle cerebral artery anastomosis(STA-MCA)in the treatment of patients with occlusive cerebrovascular disease.Methods A total of 74 patients with occlusive cerebrovascular disease admitted to our hospital were included and divided into the observation group and control group according to the random number table method,with 37 cases in each group.Patients in the control group received conservative treatment,and patients in the observation group received STA-MCA.After 3 months of follow-up,the cerebral blood flow indexes(including cerebral blood flow of anterior cerebral artery,and peak time)before treatment and 3rd day,1st month and 3rd month after treatment were observed,the modified Rankin scores before treatment and 3rd day and 1 month after treatment were recorded,and the revascularization and occurrence of complications after treatment were recorded.Results At 1 month and 3 months after treatment,the cerebral blood flow of anterior cerebral artery in the two groups increased and the peak time was shortened,and the cerebral blood flow of anterior cerebral artery in the observation group was higher than that in the control group,and the peak time was shorter than that in the control group,with statistically significant differences(P<0.05).The modified Rankin scores of the two groups 1 month after treatment were lower compared with those before treatment,and the modified Rankin score of the observation group was lower than that of the control group,with statistically significant differences(P<0.05).At 1 month after treatment,the proportions of patients with grades 0 and 1 of vascular reconstruction in the observation group were lower than those in the control group,and the proportions of patients with grades 2 and 3 were higher than those in the control group,with statistical significant differences(P<0.05).At 3 months after treatment,the proportions of patients with grades 0 and 1 of vascular reconstruction in the observation group were lower than those in the control group,and the proportion of patients with grade 3 of vascular reconstruction was higher than that in the control group,with statistically significant differences(P<0.05).There was no statistically significant difference in the total incidence of complications after treatment between the two groups(P>0.05).Conclusion STA-MCA has a good clinical effect in the treatment of patients with occlusive cerebrovascular disease,which is conducive to improving the cerebral blood flow indexes and promoting the recovery of neurological function and vascular reconstruction,with safety and reliability.

Effects of electroacupuncture combined with transcranial alternating current stimulation on inflammatory-apoptotic genes expression of MCAO rats / 中国康复医学杂志

Objective:To establish right middle cerebral artery occlusion(MCAO)model in rats and to investigate the mechanism underlying motor function regulation by transcranial alternating current stimulation(tACS)intervention.Furthermore,to dynamically observe the effects of electroacupuncture combined with tACS on neurological defi-cit scores(NDS),cerebral blood flow,inflammatory-cell apoptosis gene of MCAO model rats and to explore the mechanism of cerebral and neural regulation on motor function rehabilitation after cerebral ischemia reperfusion. Method:Forty SD rats were randomly divided into sham-operation group(S group),model group(M group),electroacupuncture group(EA group),transcranial alternating current stimulation group(T group)and electroacupuncture combined with transcranial alternating current stimulation group(EA+T group).After 2 h ischemia-reperfusion,EA group was given bilateral Qu chi(LI 11)and Zu san li(ST 36)electroacupuncture under anesthesia.Right Ml was selected for tACS in T group.EA+T group was treated with EA and tACS to-gether.S and M group were treated with anesthesia for 30min per time,for 7 days.The data from before modling(B)to after modling(D7)were recorded,including neurological deficit score and blood flow of the right middle cerebral artery by laser doppler flowmetry.RT-PCR was used to analyze inflammation-cell apopto-sis gene expression at D7. Result:Neurological deficit score:at 2h,D1,M group,EA group,T group and EA+T group increased signifi-cantly compared with other time(P＜0.05).At D3,D5,D7,S group decreased significantly compared with oth-er time(P＜0.05),while M group increased significantly compared with other group(P＜0.05).EA group,T group and EA+T group were significantly different in all times(P＜0.05).At 2h,D1,D3,D5,D7,M group increased significantly compared with B.At D1,D3,D5,D7,NDS decreased significantly compared with that at 2h(P＜0.05).Blood flow:EA+T group and S group decreased at 2h,increased at D1 and decreased at D3.EA group increased at D3.However,M group decreased significantly compared with other group at D1,D3 and D5(P＜0.05).RT-PCR:motor cortex △Ct analysis:Caspase 12 in EA+T group decreased significantly compared with T group(P＜0.05),IL-1β and NLRPla in EA group and T group decreased significantly com-pared with those in S group(P＜0.05).2-△△Ct analysis in ischemic region:ATF4 in M group increased significant-ly compared with that in other groups(P＜0.05);Bcl 2 in M group increased significantly compared with that in S group,EA group and EA+T group(P＜0.05);Bax,Caspase 12,C-fos in M group increased significantly compared with those in S Group(P＜0.05). Conclusion:Electroacupuncture combined with tACS can modulate the inflammatory response and inhibit cell apoptosis through regulating ATF4、Bcl-2、Bax、Caspase 12、C-fos and can be a new strategy for the treatment of ischemic stroke.

Valores de referencia del Doppler fetal en el Instituto Nacional de Parinatología Isidro Espinosa de los Reyes / Reference values of fetal Doppler at the Instituto Nacional de Perinatología Isidro Espinosa de los Reyes

Resumen OBJETIVO: Establecer los valores de referencia del índice de pulsatilidad con Doppler pulsado en la valoración materna y fetal de los embarazos en seguimiento entre las 18 y 39 semanas de gestación. MATERIALES Y MÉTODOS: Estudio descriptivo y transversal, efectuado en pacientes con embarazo único, entre las 18 a 40 semanas, que acudieron al Departamento de Medicina Materno Fetal del Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, entre los meses de septiembre de 2017 a mayo de 2018. La evaluación Doppler se practicó con medición del índice de pulsatilidad de las arterias uterinas, umbilical, cerebral media y conducto venoso en cada semana del embarazo. Se crearon tablas de referencia para cada semana de la gestación y se establecieron los percentiles 3, 5, 10, 90 y 95. RESULTADOS: Se registraron 862 pacientes. Los valores del índice de pulsatilidad de la arteria umbilical reportaron 17% en semanas tempranas de la gestación y 21% en edades gestacionales mayores. Los valores de la arteria umbilical fueron 3% menores en edades gestacionales tempranas y 10% menores al término del embarazo; 20% para la arteria umbilical, 15% para el conducto venoso y 10% para la arteria cerebral media. Los valores del índice de pulsatilidad medio de las arterias uterinas fueron mayores un 3% en edades gestacionales tempranas y 28% menores al término del embarazo. CONCLUSIONES: Los hallazgos de este estudio sugieren diferencias significativas con las poblaciones de Europa y Norteamérica; incluso difieren de los valores de referencia utilizados en la actualidad en la población mexicana, lo que supone una subestimación de las condiciones fetales o maternas al hacer las evaluaciones de la unidad fetoplacentaria.

Abstract OBJECTIVE: Establish the reference values for the pulsatility index using pulsed Doppler in the maternal and fetal assessment of pregnancies followed at 18 and 39 weeks of gestation. MATERIALS AND METHODS: Descriptive and cross-sectional study, carried out in patients with a singleton pregnancy, between 18 and 40 weeks, who attended the Department of Maternal Fetal Medicine of the National Institute of Perinatology, from September 2017 to May 2018. The Doppler evaluation was performed, with measurement of the pulsatility index of the uterine, umbilical, middle cerebral arteries, and venous duct in each week of pregnancy. Reference tables were created for each gestational age, establishing percentiles 3, 5, 10, 90 and 95. RESULTS: A total of 862 patients were registered. The umbilical artery pulsatility index values were reported to be 17% at early gestational ages and 21% at older gestational ages; Umbilical artery values were 3% lower at early gestational ages and 10% lower at term of pregnancy; 20% for the umbilical artery, 15% for the ductus venosus and 10% for the middle cerebral artery. The values of the mean pulsatility index of the uterine arteries were 3% higher at early gestational ages and 28% lower at the end of pregnancy. CONCLUSIONS: The findings of this study suggest significant differences with the populations of Europe and North America; They even differ from the reference values currently used in the Mexican population, which represents an underestimation of fetal and/or maternal conditions when carrying out evaluations of the feto-placental unit.

Reading and writing from right to left after anterior cerebral artery stroke / Escrita e leitura da direita para a esquerda após lesão cerebral

ABSTRACT. This is the case report of a woman who started to write and read from right to left after anterior cerebral artery stroke, affecting the left supplementary motor area. No cases were found in the literature with exactly the same characteristics. She has been able to read and write faster after rehabilitation approach at Sarah Network of Rehabilitation Hospitals, in the Belo Horizonte city unit, Brazil, despite the maintenance of the inversion. She returned to her previous activities in an adaptive way. It was discussed how the dysfunction in this cerebral area and its connections may disturb the reading strategy and direction.

RESUMO. Relato do caso de uma mulher que passou a escrever e ler da direita para a esquerda após um acidente vascular encefálico isquêmico de artéria cerebral anterior, acometendo área motora suplementar esquerda. Não foram encontrados casos na literatura exatamente com as mesmas características. Durante a participação da paciente no programa de reabilitação neurológica da Rede Sarah de Hospitais de Reabilitação, unidade Belo Horizonte, foram observados ganhos na agilidade de leitura e escrita, ainda que mantendo a inversão, e retorno às suas atividades de forma adaptada. Realizou-se discussão de como o comprometimento dessa área e de suas conexões pode perturbar a estratégia de leitura e sua direção.

Effects of antenatal corticosteroids on fetal hemodynamics: a longitudinal study / Efeitos do corticoide antenatal na hemodinâmica fetal: um estudo longitudinal

Abstract Objective: To study the effect of antenatal corticosteroid administration on fetal hemodynamics using longitudinal analysis of Doppler waveforms in the umbilical artery (UA) and middle cerebral artery (MCA). Materials and Methods: This was a retrospective study that included 30 fetuses at risk for preterm birth. Twenty-eight pregnant women were treated with betamethasone for fetal lung maturation. Doppler examinations of the UA and MCA were performed once before and three or eight times after corticosteroid administration. We used a Bayesian hierarchical linear model. Reference ranges were constructed, and associations between variables (gestational age and pre-eclampsia) were tested. Results: The mean maternal age, gestational age at betamethasone administration, and gestational age at delivery were 32.6 ± 5.89 years, 30.2 ± 2.59 weeks, and 32.9 ± 3.42 weeks, respectively. On UA Doppler, there was a significant decrease in the pulsatility index (PI) after corticosteroid administration, with a mean of 0.1147 (credibility interval: 0.03687-0.191) in three observations and a median of 0.1437 (credibility interval: 0.02509-0.2627) in eight observations. However, there was no significant change in the Doppler MCA PI, regardless of gestational age and the presence or absence of pre-eclampsia. Conclusion: Although antenatal corticosteroid administration induced a significant decrease in the Doppler UA PI, we observed no change in the cerebral vasculature.

Resumo Objetivo: Estudar o efeito da administração antenatal de corticosteroides na hemodinâmica fetal mediante análise longitudinal do Doppler na artéria umbilical e artéria cerebral média (ACM). Materiais e Métodos: Este foi um estudo retrospectivo que incluiu 30 fetos com risco de nascimento pré-termo. Vinte e oito gestantes foram tratadas com betametasona para maturação pulmonar fetal. Os exames de Doppler da AU e da ACM foram realizados uma vez antes e depois da administração de corticosteroides, num total de três ou oito observações. Utilizamos o modelo linear hierárquico com abordagem Bayesiana. Foram construídos os intervalos de referência e testadas associações entre variáveis (idade gestacional e pré-eclâmpsia). Resultados: A média ± desvio-padrão da idade materna, idade gestacional na administração de betametasona e idade gestacional no parto foram 32,6 ± 5,89 anos, 30,2 ± 2,59 semanas e 32,9 ± 3,42 semanas, respectivamente. No Doppler da AU, verificou-se diminuição significativa do índice de pulsatilidade (IP) com a terapêutica com corticosteroides (média: 0,1147 [0,03687-0,191]; em três observações) (mediana: 0,1437 [0,02509-0,2627]; em oito observações). No entanto, não foi observada alteração significativa no IP do Doppler da ACM, independentemente da idade gestacional e do diagnóstico de pré-eclâmpsia. Conclusão: Os corticosteroides pré-natais induziram diminuição significativa no IP do Doppler da AU, mas não houve alteração na vasculatura cerebral.

Morphometry of the Middle Cerebral Arteries: A Radio-Anatomical Study Based on Computed Tomography Angiography Findings / Morfometría de las Arterias Cerebrales Medias: Un Estudio Anátomo-Radiológico Basado en los Hallazgos de la Angiografía por Tomografía Computada

SUMMARY: Middle cerebral artery (MCA), which has the largest irrigation area of the arteries that feed the brain, is an important artery whose microanatomy should be well known because of its vascular variation. In pathologies which are known to affect the cerebrovascular system such as type 2 diabetes mellitus (T2DM) and hypertension, morphometric characteristics of MCA gain importance. The aim of this study is to compare the morphometric characteristics of M1 segment of MCA in T2DM and hypertensive patients with those of healthy control group by using computed tomographic angiography (CTA). The study was carried out with retrospective morphometric analysis of CTA images of 200 individuals between 40 and 65 years of age. The individuals were grouped in four as hypertensive patients (group 1), patients with T2DM (group 2), patients with hypertension and T2DM (group 3) and healthy control group (group 4). Length and diameter measurements of M1 segment were performed and recorded by using 3D CTA images. While statistically significant difference was found between bilateral M1 segment diameters of both women and men (p0.05). As a result of the post hoc analysis performed, it was concluded that right and left M1 segment diameter of group 1, group 2 and group 3 was found to be different from group 4 in both sexes (p<0.05). We believe that this study will both be a guide in radio-anatomic assessments to be performed and also increase microanatomic level of information in the surgical treatment of the artery by showing the morphometric changes that occur in M1 segment of MCA in T2DM diseases.

La arteria cerebral media (ACM), que otorga la mayor área de irrigación de las arterias que alimentan el cerebro, es un vaso importante cuya microanatomía debe ser bien conocida por su variación vascular. En patologías que afectan al sistema cerebrovascular, como la diabetes mellitus tipo 2 (DM2) y la hipertensión, las características morfométricas de la ACM cobran importancia. El objetivo de este estudio fue comparar las características morfométricas del segmento M1 de la ACM en pacientes con DM2 e hipertensos con las del grupo control sano mediante el uso de angiografía por tomografía computada (TC). El estudio fue realizado através de análisis morfométrico retrospectivo de imágenes de TC de 200 individuos entre 40 y 65 años de edad. Los individuos fueron divididos en cuatro grupos, como pacientes hipertensos (grupo 1), pacientes con DM2 (grupo 2), pacientes con hipertensión y DM2 (grupo 3) y grupo control sano (grupo 4). Las mediciones de longitud y diámetro del segmento M1 se realizaron y registraron utilizando imágenes 3D TC. Si bien se encontraron diferencias estadísticamente significativas entre los diámetros bilaterales de los segmentos M1 de mujeres y hombres (p0,05). Como resultado del análisis post hoc realizado, se concluyó que el diámetro de los segmentos M1 derecho e izquierdo del grupo 1, grupo 2 y grupo 3 fue diferente del grupo 4 en ambos sexos (p<0.05). Creemos que este estudio será una guía en las evaluaciones anátomo-radiológicas y también mejorará el nivel de información microanatómica en el tratamiento quirúrgico al mostrar los cambios morfométricos que ocurren en el segmento M1 de la ACM en las enfermedades con DM2.

Radiodensidad de la arteria cerebral media y su correlación con el nivel de hemoglobina en pacientes con y sin infarto cerebral residentes a gran altitud

Introducción. El signo de la arteria cerebral media (ACM) hiperdensa evaluada por tomografía simple permite predecir la enfermedad vascular cerebral isquémica (EVCi) con oclusión de un gran vaso, sin embargo, es frecuente identificar este signo en pobladores con niveles altos de hemoglobina sin clínica de EVCi. Objetivos. Evaluar la correlación entre la radiodensidad de la ACM y el nivel de hemoglobina en pacientes con y sin EVCi, residentes en una ciudad a gran altitud. Métodos. Estudio observacional analítico, se incluyeron personas residentes de Cusco (ubicada a 3300 msnm) que acudían al servicio de emergencia y se les realizó una tomografía cerebral, presentando o no clínica de EVCi. Se realizó la medición de la radiodensidad de la ACM y se correlacionó con el nivel de hemoglobina. Resultados. Se incluyeron 279 pacientes, el promedio de hemoglobina fue de 15,1 mg/dL y desviación estándar (DE) de 2,5 mg/dL, en los controles se identificó una correlación significativa (r = 0,425, p<0,01) entre la radiodensidad de la ACM con el nivel de hemoglobina. En los casos con EVCi derechos, la radiodensidad de la ACM derecha fue de 46,9 (DE = 7,7 UH) y de la izquierda fue de 46,1 (DE = 6,6 UH), sin que existan diferencias estadísticas (p = 0,24). Tampoco se encontró diferencias en los casos con EVCi izquierdos. Conclusión. Sí existe una correlación entre la radiodensidad de la ACM con el nivel de hemoglobina en los pobladores que viven a gran altitud, sin embargo, no se logró demostrar diferencias significativas entre la radiodensidad entre las ACM afectada y la contralateral en los casos de un EVCi.

Introduction. The sign of the hyperdense middle cerebral artery (MCA) evaluated by simple tomography allows predicting ischemic cerebrovascular disease (ICD) with occlusion of a large vessel, however, it is common to identify this sign in residents with high hemoglobin levels without symptoms of ICD. Objectives. To evaluate the correlation between the radiodensity of the MCA and the hemoglobin level in patients with and without ICD, residing in a high-altitude city. Methods. Analytical observational study, including people residing in Cusco (located at 3300 masl) who attended the emergency service and underwent a brain tomography, presenting or not ICD symptoms. ACM radiodensity was measured and correlated with the hemoglobin level. Results. 279 patients were included, the average hemoglobin was 15.1 and standard deviation (DE) of 2.5 mg/dL, in the controls a significant correlation was identified (r = 0.425, p<0.01) between the radiodensity of the MCA with the hemoglobin level. In the cases with right ICD, the radiodensity of the right MCA was 46.9 (DE = 7.7 HU) and of the left it was 46.1 (DE = 6.6 HU), with no statistical differences (p=0 ,24). No differences were found in the cases with left ICD either. Conclusion. There is a correlation between the radiodensity of the MCA with the hemoglobin level in the inhabitants who live at high altitudes, however, it is not possible to demonstrate significant differences between the radiodensity between the affected MCA and the contralateral one in the cases of an ICD.

Outcomes of decompressive craniectomy for malignant middle cerebral artery stroke in an academic hospital in Brazil / Desfechos da craniectomia descompressiva para infarto maligno da artéria cerebral média em um hospital acadêmico no Brasil

Abstract Background Ischemic stroke is an important cause of death in the world. The malignant middle cerebral artery infarction (MMCAI) has mortality as high as 80% when clinically treated. In this setting, decompressive craniectomy is a life-saving measure, in spite of high morbidity among survivors. Objective To evaluate the outcomes of patients with MMCAI treated with decompressive craniectomy in a Brazilian academic tertiary stroke center. Methods A prospective stroke database was retrospectively evaluated, and all patients treated with decompressive craniectomy for MMCAI between January 2014 and December 2017 were included. The demographics and clinical characteristics were evaluated. The functional outcome, measured by the modified Rankin Scale (mRS), was assessed at hospital discharge, after 3-months and 1-year of follow-up. Results We included 53 patients on the final analysis. The mean age was 54.6 ± 11.6 years and 64.2% were males. The median time from symptoms to admission was 4.8 (3-9.7) hours and the mean time from symptoms to surgery was 36 ± 17 hours. The left hemisphere was the affected in 39.6%. The median NIHSS at admission was 20 (16-24). The in-hospital mortality was 30.2%. After a median of 337 [157-393] days, 47.1% of patients had achieved favorable outcome (mRS ≤ 4) and 39.6% had died. Conclusion Decompressive craniectomy is a life-saving measure in the setting of MMCAI, and its effects remains important in the scenario of a middle-income country in real-world situations.

Resumo Antecedentes O acidente vascular cerebral (AVC) isquêmico é uma causa importante da morte em todo o mundo. O infarto maligno da artéria cerebral média (IMACM) tem mortalidade de até 80% quando tratado clinicamente. Nesse contexto, a craniectomia descompressiva é uma medida salvadora de vidas, apesar da alta morbidade entre os sobreviventes. Objetivo Avaliar os desfechos dos pacientes com IMACM tratados com craniectomia descompressiva em um centro acadêmico terciário de AVC no Brasil. Métodos Um banco de dados prospectivo de AVC foi avaliado retrospectivamente e todos os pacientes tratados com craniectomia descompressiva para IMACM entre janeiro de 2014 e dezembro de 2017 foram incluídos. As características clínicas e demográficas foram avaliadas. Os desfechos funcionais, medidos pela escala modificada da Rankin (mRS), foram avaliados na alta hospitalar, após 3 meses e após 1 ano de seguimento. Resultados Foram incluídos 53 pacientes na análise final. A idade média foi 54,6 ± 11,6 anos e 64,2% eram homens. A mediana do tempo dos sintomas à admissão foi 4,8 (3-9,7) horas e o tempo médio dos sintomas à cirurgia foi 36 ± 17 horas. O hemisfério esquerdo foi o afetado em 39,6%. A pontuação na escala de AVC do National Institute of Health (NIHSS) à admissão foi 20 (16-24). A mortalidade hospitalar foi 30,2%. Após uma mediana de 337 (157-393) dias, 47,1% dos pacientes tinham atingido um desfecho favorável (mRS ≤ 4) e 39,6% tinham morrido. Conclusão Craniectomia descompressiva é uma medida salvadora de vidas no contexto do IMACM e seus efeitos permanecem importantes no cenário de um país em desenvolvimento em situação de vida real.

The prevalence, clinical characteristics, and brain MRI changes in intracranial artery hypoplasia: a retrospective single-center cross-sectional study

reduced cerebral blood flow, increased atherosclerosis, and aneurysm formation. This study aimed to describe the profile of vertebral artery hypoplasia (VAH), anterior CAH (ACAH), and posterior CAH (PCAH) in symptomatic subjects. Methods: This was a retrospective cross-sectional study using medical record in a secondary private hospital in Jakarta, Indonesia, in January-December 2022. The inclusion criteria were age ?18 years with neurological symptoms, underwent brain MRI, and being diagnosed with CAH using DSA. The exclusion criteria were findings of other vascular pathologies including dissection and >50% intracranial vessel stenosis. Demographics of age, sex, body mass index (BMI), hypertension, diabetes, cardiac disorder, and previous stroke were analyzed among VAH, PCAH, and ACAH groups. Results: Of 769 subjects with clinical symptoms undergoing DSA, there were 66 (8.6%) cases of intracranial artery hypoplasia, including VAH (4.6%), PCAH (1.2%), and ACAH (2.9%). Subjects were predominantly old (53.2±10.1 years), male (53.0%), with BMI of 24.9±3.9 kg/m2 and hypertension (69.7%). Previous stroke (69.7%) was more prevalent than in previous study (28.1%). Stroke and brain ischemic lesion were detected in 89.4% and 84.8% cases. No differences were found in all parameters among all groups, but posterior circulation symptoms tended to be found in VAH (28.1%) than general stroke (20.3%). Conclusions: The high percentage of recurrent stroke and corresponding clinical symptoms associated with CAH supported that CAH may be a risk factor for clinical symptoms, including stroke, regardless of the involved artery.

Cerebroplacental ratio and its relation to poor perinatal outcomes in singleton pregnancies: a cross sectional study in a tertiary care centre of Eastern India

Background: Detection of fetal growth abnormalities by fetal monitoring is a critical component of perinatal care. Cerebroplacental ratio (CPR), as measured by colour Doppler, has recently been demonstrated to be a reliable indicator of foetus health. CPR is calculated as ratio of pulsatility index of middle cerebral artery (MCA) and umbilical artery (UA). When blood is redistributed in the early stages of hypoxia in favour of cerebral circulation, the diastolic flow amplitude increases above normal levels in MCA while umbilical flow in diastole decreases, providing CPR. This study aims to investigate the relationship between CPR and adverse perinatal outcomes.Methods: After institutional ethical approval, a 2-year study was conducted on 226 pregnant women of age group 18-45 years with singleton pregnancies at 34-38 weeks with informed consent in a tertiary hospital in Eastern part of India. The MCA and UA pulsatility index were calculated using a doppler scan on each patient. When the cerebroplacental ratio is <1 it is deemed abnormal. The perinatal outcomes were observed and their associations were evaluated.Results: There were 68/226 (30%) women had abnormal CPR (<1). CPR<1 was significantly associated with unfavourable perinatal outcomes (prematurity, low birth weight, NICU admission and perinatal hypoxia) with p value < 0.001.Conclusions: CPR is important tool in predicting an unfavourable perinatal outcome.

Time course of hemispheric cerebral volume after decompressive craniectomy in malignant middle cerebral artery stroke / Evolução temporal do volume hemisférico cerebral após craniectomia descompressiva em infarto maligno de artéria cerebral média

Abstract Background Brain edema is the leading cause of death in patients with malignant middle cerebral artery (MCA) infarction. Midline shift (MLS) has been used as a monohemispheric brain edema marker in several studies; however, it does not precisely measure brain edema. It is now possible to directly measure hemisphere brain volume. Knowledge about the time course of brain edema after malignant middle cerebral artery infarction may contribute to the condition's management. Objective Therefore, our goal was to evaluate the course of brain edema in patients with malignant MCA infarction treated with decompressive craniectomy (DC) using hemispheric volumetric measurements. Methods Patients were selected consecutively from a single tertiary hospital between 2013 and 2019. All patients were diagnosed with malignant middle cerebral artery infarction and underwent a decompressive craniectomy (DC) to treat the ischemic event. All computed tomography (CT) exams performed during the clinical care of these patients were analyzed, and the whole ischemic hemisphere volume was calculated for each CT scan. Results We analyzed 43 patients (197 CT exams). Patients' mean age at DC was 51.72 [range: 42-68] years. The mean time between the ischemic ictus and DC was 41.88 (range: 6-77) hours. The mean time between the ischemic event and the peak of hemisphere volume was 168.84 (95% confidence interval [142.08, 195.59]) hours. Conclusion In conclusion, the peak of cerebral edema in malignant MCA infarction after DC occurred on the 7th day (168.84 h) after stroke symptoms onset. Further studies evaluating therapies for brain edema even after DC should be investigated.

Resumo Antecedentes O edema cerebral é a principal causa de morte em pacientes com infarto maligno de artéria cerebral média. O desvio da linha média tem sido utilizado como marcador de edema cerebral mono-hemisférico em alguns estudos; porém, ele não mede de forma precisa o edema cerebral. Atualmente é possível mensurar diretamente o volume do hemisfério cerebral. O conhecimento sobre a evolução temporal do edema cerebral após infartos malignos da artéria cerebral média pode contribuir para o cuidado clínico desta condição. Objetivo Nosso objetivo é avaliar o edema hemisférico ao longo do tempo, em pacientes com infarto maligno da artéria cerebral média, tratados com craniectomia descompressiva. Métodos Os pacientes foram selecionados de forma consecutiva, em um hospital terciário, entre 2013 e 2019. Todos os pacientes apresentavam diagnóstico de infarto maligno de artéria cerebral média e foram submetidos a craniectomia descompressiva. Todas as tomografias computadorizadas de crânio destes pacientes foram analizadas, e o volume do hemisfério cerebral infartado foi mensurado. Resultados Analisamos 43 pacientes (197 tomografias de crânio). A idade média dos pacientes na craniectomia descompressiva foi 51,72 (42-68) anos. O tempo médio entre o ictus e a craniectomia descompressiva foi 41,88 (6-77) horas. O tempo médio entre o ictus e o pico do volume hemisférico foi 168,84 (142,08-195,59) horas. Conclusão O pico do volume cerebral em pacientes com infarto maligno de artéria cerebral média submetidos a craniectomia descompressiva ocorreu no 7o dia (168,84 horas) após o infarto. Mais estudos avaliando terapêuticas direcionadas ao edema cerebral seriam úteis neste contexto.

Doppler Indices of the Fetal Middle Cerebral and the Umbilical Arteries in Pregnancies at High Risk Followed Up for Suspected Fetal Growth Restriction

Background: Fetal growth restriction is related to compromised perinatal outcomes. The screening and prevention tools for fetal growth restriction like Doppler indices in high-risk groups compared with general antenatal populations. An evaluation of the correlation between Doppler indices and placental weight and birth weight of the neonate at term pregnancy in high-risk pregnancies is essential. For the early detection of fetal growth limitations in high-risk pregnancies, sensitive screening techniques are few. Objectives: To determine the most accurate indicator for predicting a poor perinatal outcome or intrauterine growth restriction by comparing and correlating the modifications in Doppler ultrasound studies of fetal circulation in general pregnant women with those of high-risk patients both with and without intrauterine growth retardation. Study design: A cross-sectional research including 81 healthy pregnancies and 19 high-risk patients at 31–40 weeks of gestation was conducted. The pulsatility index (PI) of the middle cerebral artery (MCA), the umbilical artery (UA), and the MCA PI to UA PI ratio were all analyzed. We compared the Doppler indices’ mean values. Then these values were correlated with placental weight and birth weight of the offspring. Results: A significantly low birth weight and less fetoplacental ratio and placental coefficient ratio were found in high-risk cases than in normal pregnant women (P <0.05). A strong positive relationship was observed between the middle cerebral artery pulsatility index and placental weight, while negative relationship between the pulsatility index of the middle cerebral artery and the Feto-placental ratio (P < 0.05). In addition, a positive association was found between the pulsatility index of the middle cerebral artery and placental coefficient, whereas a negative correlation was observed between the Cerebro-placental ratio and Feto-placental ratio in high-risk cases (P <0.05). Conclusion: Low birth weight can be predicted using Doppler indices since there is a definite correlation between it and unfavorable perinatal outcomes.

Intervention effect and mechanism of Zhongfeng yure decoction on ischemic stroke model rats / 中国药房

OBJECTIVE To study the intervention effect and mechanism of Zhongfeng yure decoction on ischemic stroke model rats. METHODS Totally 85 rats were randomly divided into sham operation group （normal saline， n＝15）， model control group （normal saline， n＝18）， Nimodipine tablet group （positive control， 10.8 mg/kg， n＝18）， high-dose group of Zhongfeng yure decoction （20.52 g/kg， n＝17） and low-dose group of Zhongfeng yure decoction （5.13 g/kg， n＝17）， respectively. After 7 days of preventive continuous administration （once a day）， except for the sham operation group， the rats’ middle cerebral artery occlusion （MCAO） model was established by the modified suture method in other groups. After modeling， the rats in each group continued to be administered for 3 days. During experiment， general condition of the rats was observed， and the neurological function score was performed. After the last administration， the organ index was calculated， the cerebral infarction area and pathological changes of brain tissue were observed. The levels of tumor necrosis factor-α （TNF-α） and interleukin 6 （IL-6） in brain tissue and serum， and the average optical density value of caspase-3 and phosphorylated protein kinase B（p-AKT） protein in brain tissue were detected. RESULTS Three days after modeling， compared with sham operation group， the neurological function score， in brain tissue index， spleen tissue index， proportion of cerebral infarction area， the levels of TNF-α and IL-6 in brain tissue and serum， and the average optical density value of caspase-3 protein in brain tissue were significantly increased in the model control group （P＜0.05 or P＜0.01）； karyopyknosis， diffuse edema and other lesions appeared in brain tissue. Compared with the model control group， the above indexes in each administration group were improved to varying degrees. Among them， there were significant regression in brain tissue index， spleen tissue index， proportion of cerebral infarction area， TNF-α level in brain tissue and serum， and the average optical density values of caspase-3 protein and p-AKT protein in brain tissue of rats in high-dose group of Zhongfeng yure decoction （P＜0.05 or P＜0.01）. CONCLUSIONS Zhongfeng yure decoction has a certain intervention and therapeutic effect on MCAO model rats. The mechanism may be to reduce the secretion of inflammatory factors TNF-α and IL-6， down-regulate the expression of caspase-3 protein in ischemic brain tissue， up-regulate the expression of p-AKT protein， so as to protect the neurons.

Protective Effect of Huazhuo Jiedu Huoxue Tongluo Prescription on Cerebral Ischemia-reperfusion Injury via Regulating Autophagy Based on JNK Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism of Huazhuo Jiedu Huoxue Tongluo prescription in alleviating cerebral ischemia-reperfusion injury via regulating nerve cell autophagy based on c-Jun N-terminal kinase（JNK）signaling pathway . MethodSixty SD rats were randomly divided into 6 groups： sham group， middle cerebral artery occlusion/reperfusion （MCAO/R） group （model group）， Huazhuo Jiedu Huoxue Tongluo prescription group ［traditional Chinese medicine （TCM） group（25.0 g·kg-1）］， JNK inhibitor SP600125 （SP） group（5 mg·kg-1）， TCM+SP group and JNK agonist Anisomycin （Ani） group（15 mg·kg-1）. After 24 h of modeling， TCM group and TCM+SP group were given TCM decoction （ig） for 3 consecutive days， and the other groups were given equal volume of normal saline （ig）. Neurological deficit was evaluated by neurological function score and cerebral infarct volume was determined by 2，3，5-triphenyltetrazole chloride （TTC） staining. Hematoxylin-eosin （HE） staining and Nissl staining were used to observe the structural changes of brain tissue and the damage of neurons， respectively. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay （TUNEL） was performed to detect cell apoptosis. The ultrastructure of autophagosomes was observed by transmission electron microscope. Western blot was employed to detect the protein expressions of microtubule-associated protein 1 light chain 3A/B （LC3A/B）， autophagy related 5 （Atg5）， the ortholog of yeast Atg6 （Beclin1）， p62， B-cell lymphoma 2 （Bcl-2）， JNK， phosphorylated （p）-JNK and c-Jun in brain tissue. The mRNA expressions of LC3A/B， Beclin1， p62， Atg5， Bcl-2， JNK and c-Jun were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the sham group， the model group had elevated neurological deficit score （P<0.05）， enlarged cerebral infarct volume （P<0.05）and typical infarction manifestations formed in hippocampal region and its surrounding brain tissue. In addition， there were a large number of neuronal cell degeneration， necrosis， liquefaction， nucleus pyknosis and deep staining， and inflammatory cell infiltration in the cortex in the model group， and severe swelling of mitochondria， lysosomes， autophagosomes and autophagolysosomes were clearly seen under electron microscope. TUNEL positive cells were increased （P<0.05）， and cell apoptosis was severe. The nuclear membrane and nucleolus of neurons in brain tissue were blurred with discontinuous processes， and Nissl bodies in cytoplasm were stained light with reduced number. Western blot revealed that the model group had up-regulated protein expressions of LC3A/B， Beclin1， Atg5， JNK， p-JNK and c-Jun in brain tissue （P<0.05）， while down-regulated protein expressions of p62 and Bcl-2 （P<0.05）as compared with the sham group. Real-time PCR indicated that the mRNA expressions of LC3A/B， Beclin1， Atg5， JNK and c-Jun in the model group were higher （P<0.05） while the mRNA expressions of p62 and Bcl-2 were lower （P<0.05） than those in the sham group. Compared with the conditions in model group， the neurological deficit scores of TCM， SP and TCM+SP groups were lowered （P<0.05）， and the cerebral infarct volume was reduced （P<0.05）， with improved pathological status of brain tissue， especially in the TCM group. Furthermore， there were abundant and basically normal mitochondrial cristae， slightly dilated endoplasmic reticulum， slightly swollen golgi apparatus， slightly fused nuclear membrane， and few visible lysosomes， autophagosomes and autophagolysosomes. TUNEL positive cells were decreased （P<0.05）， displaying reduced apoptosis， especially in the TCM group. The nucleolus and nuclear membrane of neurons in brain tissue were discernible， and Nissl bodies in cytoplasm was reduced to a certain degree as compared with those in the model group. Western blot showed a decrease in the protein expressions of LC3A/B， Beclin1， Atg5， JNK， p-JNK and c-Jun in the TCM group ，the SP group，and the TCM+SP group（P<0.05），while an increase in the protein expressions of p62 in the TCM group and SP group（P<0.05），and an increase in the protein expressions of Bcl-2 in the TCM group and TCM+SP group. By Real-time PCR， the mRNA expressions of LC3A， LC3B， Beclin1， Atg5， JNK and c-Jun had a down-regulation（P<0.05） while the mRNA expression of p62 a up-regulation in the TCM group ，the SP group，and the TCM+SP group（P<0.05），and the mRNA expression of Bcl-2 a up-regulation in the TCM group and the TCM+SP group（P<0.05）.Scores of the Ani group were raised （P<0.05）， and infarct volume was increased significantly， with aggravated neuronal cell necrosis and obvious inflammatory infiltration. Moreover， there were neuronal nuclear membrane fusion with abnormal protrusion， increased heterochromatin aggregation in edge， severe mitochondrial swelling， endoplasmic reticulum expansion， increased lysosomes， increased intracytoplasmic vesicles， and visible autophagosomes and autophagolysosomes. TUNEL positive cells were increased （P<0.05）， representing severe apoptosis. The number of Nissl bodies dropped with light staining， and the nucleolus and nuclear membrane were blurred. Real-time PCR found that the mNRA expressions of Atg5， c-Jun， JNK were up-regulated （P<0.05），while Beclin1， p62， Bcl-2 were were down-regulated in the Ani group （P<0.05）. Compared with the TCM group and SP group，the protein expressions of LC3A/B， Beclin1， Atg5， JNK， p-JNK， c-Jun were decreased，and p62， Bcl-2 were increased in the Ani group（P<0.05）. Compared with the TCM group，the mRNA expressions of JNK mRNA had a down-regulation in the SP group and TCM+SP group，while LC3A， LC3B， Atg5， c-Jun， JNK had an up-regulation（P<0.05） and Bcl-2 had a down-regulation in the Ani group（P<0.05）. Compared with the SP group，the mRNA expressions of Atg5， c-Jun， JNK had an up-regulation（P<0.05）， and Beclin1， p62， Bcl-2 had a down-regulation in the Ani group（P<0.05）. ConclusionHuazhuo Jiedu Huoxue Tongluo prescription significantly up-regulates the protein and mRNA expressions of LC3A/B， Beclin1， Atg5， JNK， p-JNK and c-Jun， and down-regulates the protein and mRNA expressions of p62 and Bcl-2， suggesting that the prescription can inhibit autophagy through JNK signaling pathway to reduce ischemia/reperfusion injury in rats.

Improvement effect of diterpene ginkgolides on acute tMCAO rats and chronic tMCAO rats / 药学学报

To study the cognitive effects of diterpene ginkgolides (DG), transient middle cerebral artery occlusion (tMCAO)-induced rats were established. tMCAO-rats induced by suture method were divided into sham operation group, solvent control group, NBP group, DG group. The animal experiments in the present study were performed in accordance with the Ethical Guidelines of the Laboratory Animal Welfare Ethical Committee of Peking Union Medical College (00000646, 00000635). The effects of DG on tMCAO rats were evaluated by neurological severity score, cerebral infarction volume measurement, step-down and Morris water maze test. In the acute tMCAO rat model, 100 mg·kg-1 DG improved the neural score and infarction volume. In the chronic tMCAO rat model, DG 100 mg·kg-1 significantly improved the survival rate of tMCAO-induced rats. The Morris water maze results showed 100 mg·kg-1 DG decreased the latency of tMCAO-induced rats to find the platform, while the effect was weaker than the NBP. However, DG 30 mg·kg-1 did not show a significant effect. In conclusion, DG exerted a therapeutic effect on transient middle cerebral artery occlusion.