Effects of foraging exercise on behavior and the expression of 5-hydroxytryptamine 1A and transforming growth factor β1 in the frontal lobes of rats modelling post-stroke depression / 中华物理医学与康复杂志

Objective:To explore the effect of foraging exercise (FE) on the behavior of rats with post-stroke depression (PSD) and the expression of 5-Hydroxytryptamine 1A (5-HT1A) receptor and transforming growth factor β1 (TGF-β1) in their frontal lobes.Methods:Thirty-six healthy male Sprague-Dawley rats were randomly divided into an ischemia-reperfusion (I/R) group, a PSD group and a PSD+ FE (FE) group, each of 12. The right middle cerebral artery of each was occluded using the thread occlusion method with 1.5h of ischemia. In the PSD and FE groups, mild stimulation was administered at unpredictable intervals over 3 weeks beginning 1 week after the successful modeling. The rats in the I/R group were raised in a group. Those in the PSD group were raised in individual cages. Those in the FE group were raised in a single cage and foraged freely for a total of 4 weeks. Four and eight weeks after the modeling, the body weights were measured, and the open field, social interaction (SIT) and sugar preference tests were administered to all of the groups. Four weeks later, all of the rats were sacrificed and their brains were sliced and stained. The expression of 5-HT1A receptor and TGF-β1 in the frontal lobe was detected using western blotting.Results:One week after modeling, there was no significant difference in average body weight or the average behavioral scores among the three groups. After four weeks the PSD and FE groups had significantly lower average body weight than the I/R group, fewer counts of rearing and grid crossing, longer SIT latency, less interaction time and lower average sugar preference (all significant differences). After eight weeks the average body weight had increased in each group. SIT latency had shortened and interaction time had increased in the FE group, and the rearing and grid crossing counts and sugar preference had increased in the PSD and FE groups. At that point the FE group had significantly greater average body weight than the PSD group, more counts of rearing and grid crossing, shorter SIT latency, increased interaction time, and greater sugar preference. The ratio of residual brain volume in the right hemisphere of the PSD and FE groups was significantly lower on average than in the I/R group. However, there was no significant difference in the right residual brain volume ratio between the PSD and FE groups. Staining revealed that the pathological changes in the frontal lobes of the FE group had been significantly relieved compared with the PSD group. Eight weeks after the operation the increases in average 5-HT 1A receptor and TGF-β1 levels in the FE group were significantly greater than in the PSD group.Conclusion:Foraging can relieve the depressive symptoms of rats modeling post-stoke depression. The mechanism may be related to alleviating the pathological damage and increasing the expression of 5-HT1AR and TGF-β1 in the frontal lobe. Early chronic stress may increase the volume of cerebral infarction, at least in rats.

Relationship between 25-hydroxyvitamin D and infarction volume in patients with acute ischemic stroke in anterior circulation / 中华危重病急救医学

Objective:To investigate the correlation between the level of serum 25-hydroxyvitamin D [25(OH)D] and infarction volume in patients with acute ischemic stroke (AIS) with internal carotid artery system (anterior circulation).Methods:A prospective cohort study was conducted. Patients with AIS admitted to the department of emergency of Beijing Boai Hospital from October 2017 to September 2019 were enrolled. Nutritional risk screening 2002 (NRS 2002) were assessed in all cases within 24 hours after enrollment. Fasting venous blood was collected for biochemical analysis, including albumin (ALB), homocysteine (HCY), uric acid (UA), hypersensitive C-reactive protein (hs-CRP), etc. Serum 25(OH)D level was detected by electrochemiluminescence immunoassay. Magnetic resonance imaging (MRI) was performed to calculate the volume of cerebral infarction. According to the volume of cerebral infarction, the patients were divided into small volume (≤ 1 cm 3) group, medium volume (1 cm 3 < infarct volume < 20 cm 3) group and large volume (≥20 cm 3) group. The differences of serum 25(OH)D and other indicators in each group were compared; the influencing factors of infarct volume were analyzed by Logistic regression; and the goodness of fit of regression model was tested by Hosmer-Lemeshow (HL). Results:A total of 224 patients with AIS were enrolled, 92 in small volume group, 90 in medium volume group and 42 in large volume group, and there was no significant difference in serum 25(OH)D level among small, medium and large volume groups [μg/L: 13.21 (7.47, 19.33), 11.20 (7.00, 15.07), 9.19 (6.30, 17.10), H = 4.994, P = 0.082]. There were 124 patients with AIS in anterior circulation, 45, 56 and 23 patients in the small, medium and large volume groups, respectively, with the increase of the cerebral infarction volume, the serum 25(OH)D level in small, medium and large volume groups decreased gradually, and the difference was statistically significant [μg/L: 13.22 (9.00, 19.65), 10.41 (6.72, 14.92), 8.30 (4.70, 11.30), H = 11.068, P = 0.004]. In addition, with the increase of the cerebral infarction volume, the older the patients with AIS in anterior circulation [years old: 63.0 (54.0, 75.5), 76.0 (63.0, 84.0), 82.0 (67.5, 85.0), H = 14.981, P = 0.001], the higher the nutritional risk ratio (35.6%, 53.6%, 73.9%, χ2 = 9.271, P = 0.010), the higher the serum hs-CRP level [mg/L: 1.91 (0.92, 3.40), 4.10 (1.73, 22.42), 19.74 (4.02, 68.81), H = 21.477, P < 0.001], and the lower the ALB level (g/L: 42.30±12, 38.11±5.06, 35.14±5.49, F = 19.347, P < 0.001). After adjusting for age, gender, atrial fibrillation, nutritional risk, hs-CRP and other confounding factors, serum 25(OH)D was an independent protective factor for the infarct volume of AIS in anterior circulation [odds ratio ( OR) = 0.962, P = 0.040], For every 10 μg/L decrease of 25(OH)D, the risk of one grade increase in infarction volume was increased by 47.7% respectively (goodness of fit: χ2 = 5.357, P = 0.719). Conclusion:The low serum 25(OH)D level was associated with the increase of infarct volume in the anterior circulation cerebral infarction, and early detection of serum 25(OH)D level can help risk stratification of AIS patients.

MiR-150-5p protects rats from middle cerebral artery occlusion by inhibiting the toll-like receptor-5/nuclear factor-kappa B p65 signaling pathway / 中国组织工程研究

BACKGROUND: There is an inflammatory response in the lesion tissue of ischemic cerebral infarction, and the expression of miR-150-5p is significantly decreased. Whether miR-150-5p inhibits the release of inflammatory factors and alleviates the injury of ischemic cerebral infarction tissue through the Toll-like receptor-5/nuclear factor-KB pathway remains unclear. OBJECTIVE: To investigate the role and preliminary mechanism of miR-150-5p in ischemic cerebral infarction in rats. METHODS: (1) The rat models of middle cerebral artery occlusion were constructed and the rat models were divided into five groups: Control, miR-150-5p agomir, agomir control, miR-150-5p antagomir and antagomir control groups. (2) The rats in the control group was given the intracerebroventricular injection of normal saline, and the rats in the latter four groups were given the intracerebroventricular injection of miR-150-5p agomir (miR-150-5p agonist), agomir negative control, miR150-5p antagomir (miR150-5p inhibitor) and antagomir negative control, respectively. (3) After 7 days, the brain was graded by modified neurological severity score, the cerebral infarct volume was measured by MRI, and the histopathological changes were observed by hematoxylin-eosin staining. The expression levels of miR-150-5p, interleukin-6, tumor necrosis factor-a, Toll-like receptor-5 and nuclear factor-KB p65 in brain tissues were detected by qRT-PCR, ELISA and western blot assay, respectively. The target relationship between miR150-5p and Toll-like receptor-5 was verified by luciferase assay by retrieving the bioinformatics website Targetscan to predict the binding sites of miR-150-5p and Toll-like receptor-5. RESULTS AND CONCLUSION: (1) Compared with the control group, the modified neurological severity score, and levels of interleukin-6, tumor necrosis factor-a, Toll-like receptor-5 and nuclear factor-KB p65 proteins were significantly decreased in the miR-150-5p agomir group (P 0.05). (3) TargerScan website prediction results and luciferase reporter gene analysis results showed that miR-150-5p and Toll-like receptor-5 had a targeted binding site. (4) These results imply that miR-150-5p can inhibit the inflammatory signaling pathway of Toll-like receptor-5/nuclear factor-KB p65 in brain injury caused by ischemia and reduce the inflammatory response, thereby alleviating the damage of nerve function and playing a protective role.

Development of a three-channel automatic climbing training system for rat rehabilitation after ischemic stroke

This paper reports the development of a three-channel automatic speed-matching climbing training system that could train three rats at the same time for rehabilitation after an ischemic stroke. An infrared (IR) remote sensor was installed at the end of each channel to monitor the real-time position of a climbing rat. This research was carried out in five stages: i) system design; ii) hardware circuit; iii) running speed control; iv) functional testing; and v) verification using an animal model of cerebral stroke. The rehabilitated group significantly outperformed the middle cerebral artery occlusion (MCAo) sedentary group in the rota-rod and inclined plate tests 21 days after a stroke. The rehabilitated group also had a cerebral infarction volume of 28.34±19.4%, far below 56.81±18.12% of the MCAo group 28 days after the stroke, validating the effectiveness of this training platform for stroke rehabilitation. The running speed of the climbing rehabilitation training platform was designed to adapt to the physical conditions of subjects, and overtraining injuries can be completely prevented accordingly.

Expression and clinical significance of plasma miR-124 in acute ischemic stroke / 实用医学杂志

Objective To investigate the expression and clinical significance of plasma miR-124 in acute ischemic stroke (AIS). Methods Forty patients with AIS were collected and 40 volunteers without history of AIS were set as control. Infarction volume was detected by MRI; plasma miR-124 expression level was measured by RTPCR technique and neural function was evaluated by NIHSS scores. Results Compared with that in the control group, plasma miR-124 level in AIS group was significantly reduced (P < 0.05). Plasma miR-124 level in AIS patients with infarction volume greater than 3 cm3 was significantly lower than that of AIS patients with infarction volume less than 3 cm3 (P < 0.05). Correlation analysis showed a negative correlation between miR-124 and infarction volume (r =-0.473, P < 0.05). Plasma miR-124 level in AIS with NIHSS score higher than 5 was significantly lower than that of AIS patients with NIHSS lower than 5 (P< 0.05). NIHSS score negatively correlated with the miR-124 level of AIS patients (r =-0.567, P < 0.05). Conclusion The plasma miR-124 is significantly reduced in patients with AIS, and negatively correlated with the cerebral infarction volume and NIHSS score.

Neural Stem Cells Transfected with Leukemia Inhibitory Factor Promote Neuroprotection in a Rat Model of Cerebral Ischemia / 神经科学通报·英文版

Leukemia inhibitory factor (LIF) contributes to the neuroprotection by neural stem cells (NSCs) after ischemic stroke. Our aim was to explore whether LIF-transfected NSCs (LIF-NSCs) can ameliorate brain injury and promote neuroprotection in a rat model of cerebral ischemia. To accomplish this goal, we transfected NSCs with a lentivirus carrying the LIF gene to stably overexpress LIF. The LIF-NSCs reduced caspase 3 activation under conditions of oxygen-glucose deprivation in vitro. Transient cerebral ischemia was induced in rats by 2 h of middle cerebral artery occlusion (MCAo), and LIF-NSCs were intravenously injected at 6 h post-ischemia. LIF-NSC treatment reduced the infarction volume and improved neurological recovery. Moreover, LIF-NSCs improved glial cell regeneration and ameliorated white matter injury in the MCAo rats. The NSCs acted as carriers and increased the expression of LIF in the lesions to protect against cerebral infarction, suggesting that LIF-NSCs could be a potential treatment for cerebral infarction.

S100ß, Matrix Metalloproteinase-9, D-dimer, and Heat Shock Protein 70 Are Serologic Biomarkers of Acute Cerebral Infarction in a Mouse Model of Transient MCA Occlusion

OBJECTIVE: Diagnosing acute cerebral infarction is crucial in determining prognosis of stroke patients. Although many serologic tests for prompt diagnosis are available, the clinical application of serologic tests is currently limited. We investigated whether S100β, matrix metalloproteinase-9 (MMP-9), D-dimer, and heat shock protein 70 (HSP70) can be used as biomarkers for acute cerebral infarction. METHODS: Focal cerebral ischemia was induced using the modified intraluminal filament technique. Mice were randomly assigned to 30-minute occlusion (n=10), 60-minute occlusion (n=10), or sham (n=5) groups. Four hours later, neurological deficits were evaluated and blood samples were obtained. Infarction volumes were calculated and plasma S100β, MMP-9, D-dimer, and HSP70 levels were measured using enzyme-linked immunosorbent assay. RESULTS: The average infarction volume was 12.32±2.31 mm³ and 46.9±7.43 mm³ in the 30- and 60-minute groups, respectively. The mean neurological score in the two ischemic groups was 1.6±0.55 and 3.2±0.70, respectively. S100β, MMP-9, and HSP70 expressions significantly increased after 4 hours of ischemia (p=0.001). Furthermore, S100β and MMP-9 expressions correlated with infarction volumes (p < 0.001) and neurological deficits (p < 0.001). There was no significant difference in D-dimer expression between groups (p=0.843). The area under the receiver operating characteristic curve (AUC) showed high sensitivity and specificity for MMP-9, HSP70 (AUC=1), and S100β (AUC=0.98). CONCLUSION: S100β, MMP-9, and HSP70 can complement current diagnostic tools to assess cerebral infarction, suggesting their use as potential biomarkers for acute cerebral infarction.

S100ß, Matrix Metalloproteinase-9, D-dimer, and Heat Shock Protein 70 Are Serologic Biomarkers of Acute Cerebral Infarction in a Mouse Model of Transient MCA Occlusion

OBJECTIVE: Diagnosing acute cerebral infarction is crucial in determining prognosis of stroke patients. Although many serologic tests for prompt diagnosis are available, the clinical application of serologic tests is currently limited. We investigated whether S100β, matrix metalloproteinase-9 (MMP-9), D-dimer, and heat shock protein 70 (HSP70) can be used as biomarkers for acute cerebral infarction.METHODS: Focal cerebral ischemia was induced using the modified intraluminal filament technique. Mice were randomly assigned to 30-minute occlusion (n=10), 60-minute occlusion (n=10), or sham (n=5) groups. Four hours later, neurological deficits were evaluated and blood samples were obtained. Infarction volumes were calculated and plasma S100β, MMP-9, D-dimer, and HSP70 levels were measured using enzyme-linked immunosorbent assay.RESULTS: The average infarction volume was 12.32±2.31 mm³ and 46.9±7.43 mm³ in the 30- and 60-minute groups, respectively. The mean neurological score in the two ischemic groups was 1.6±0.55 and 3.2±0.70, respectively. S100β, MMP-9, and HSP70 expressions significantly increased after 4 hours of ischemia (p=0.001). Furthermore, S100β and MMP-9 expressions correlated with infarction volumes (p < 0.001) and neurological deficits (p < 0.001). There was no significant difference in D-dimer expression between groups (p=0.843). The area under the receiver operating characteristic curve (AUC) showed high sensitivity and specificity for MMP-9, HSP70 (AUC=1), and S100β (AUC=0.98).CONCLUSION: S100β, MMP-9, and HSP70 can complement current diagnostic tools to assess cerebral infarction, suggesting their use as potential biomarkers for acute cerebral infarction.

Lesion patterns on MRI in patients with posterior circulation infarction with different TCM syndromes / 国际中医中药杂志

Objective To study the characteristics of MRI Lesions in posterior circulation cerebral infarction and the correlation of the syndrome types of traditional Chinese medicine.Methods 82 patients with posterior circulation cerebral infarction from May 2012 to May 2015 were recruited, two observers estimated cranial MRI infarct size, location, and TCM syndrome type in the hospital medical records of the patients separately.Results Of all patients with posterior circulation cerebral infarction, patients with meridians involved infarction in the distant part of posterior circulation is far more than other parts of the posterior circulation(21 patient,P=0.006), nevertheless,patients with apoplexy involving Zang-fu organs,cerebral infarction volume is larger (14.78 ± 5.68 mlvs. 9.12 ± 6.67 ml,P=0.001).Conclusion Of all patients with posterior cerebral infarction, patients with meridians be involved, infarction in the distant part of posterior circulation is far more than other parts of the posterior circulation, nevertheless, in patients with apoplexy involving Zang-fu Organs, cerebral infarction volume is larger.

Semi-Quantitative Analyses of Hippocampal Heat Shock Protein-70 Expression Based on the Duration of Ischemia and the Volume of Cerebral Infarction in Mice

OBJECTIVE: We investigated the expression of hippocampal heat shock protein 70 (HSP-70) infarction volume after different durations of experimental ischemic stroke in mice. METHODS: Focal cerebral ischemia was induced in mice by occluding the middle cerebral artery with the modified intraluminal filament technique. Twenty-four hours after ischemia induction, both hippocampi were extracted for HSP-70 protein analyses. Slices from each hemisphere were stained with 2,3,5-triphenyltetrazolium chloride (2%), and infarction volumes were calculated. HSP-70 levels were evaluated using western blot and enzyme-linked immunosorbent assay (ELISA). HSP-70 subtype (hsp70.1, hspa1a, hspa1b) mRNA levels in the hippocampus were measured using reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Cerebral infarctions were found ipsilateral to the occlusion in 10 mice exposed to transient ischemia (5 each in the 30-min and 60-min occlusion groups), whereas no focal infarctions were noted in any of the sham mice. The average infarct volumes of the 2 ischemic groups were 22.28+/-7.31 mm3 [30-min group+/-standard deviation (SD)] and 38.06+/-9.53 mm3 (60-min group+/-SD). Western blot analyses and ELISA showed that HSP-70 in hippocampal tissues increased in the infarction groups than in the sham group. However, differences in HSP-70 levels between the 2 infarction groups were statistically insignificant. Moreover, RT-PCR results demonstrated no relationship between the mRNA expression of HSP-70 subtypes and occlusion time or infarction volume. CONCLUSION: Our results indicated no significant difference in HSP-70 expression between the 30- and 60-min occlusion groups despite the statistical difference in infarction volumes. Furthermore, HSP-70 subtype mRNA expression was independent of both occlusion duration and cerebral infarction volume.

Effect of Morroniside on Cerebral Infarction Volume in Focal Cerebral Ischemia-reperfusion Rats / 中国康复理论与实践

@#Objective To observe the effect of morroniside on cerebral infarction volume in focal cerebral ischemia-reperfusion rat model.Methods The animal model was induced by occlusion of middle cerebral artery with suture embolus, ischemia for 30 minutes, and reperfusion for 7 days. The infarction volume was measured by 2,3,5-triphenyltetrazolium chloride(TTC) staining technique.Results Compared with sham operation group, the cerebral infarction volume ratios increased obviously in model group and in the drug-treated（90 mg/kg，270 mg/kg）groups. Compared with model group, the cerebral infarction volume ratios decreased obviously in the morroniside-treated（90 mg/kg，270 mg/kg）group,while the cerebral infarction volume ratios in vitamin E-treated（35 mg/kg）group didn't change.Conclusion Morroniside may decrease the cerebral infarction volume after cerebral ischemia-reperfusion. It possesses protective effect against cerebral ischemia-reperfusion injury.

Experimental study of the therapeutic effectiveness of defibrase on treating acute cerebral ischemia and the effectiveness in different administrated ways / 中国康复理论与实践

@#ObjectiveTo investigate the intensity of degrading plasma fibrinogen(FIB) and the therapeutic effectiveness of defibrase on treating cerebral ischemia by different administrated ways. MethodsIntraluminal suture method was used to develop reversible middle cerebral artery occlusion (MACO). 154 healthy male Wistar rats were randomized into 2 groups. The rats in intravenous treatment group were injected defibrase intravenously at 0.5,3,6,9,12hours after MACO,while the rats in coeliac treatment group were injected defibrase by abdominocentesis. Meanwhile the control group received normal saline. All rats were killed at 24 hours after MCAO. The thrombus in middle cerebral artery (MCA) and cerebral infarction were examined microscopically in HE stained sections. Infarction volume was measured by using 2,3,5-triphenyltetrazolium chloride staining. 24 rats were selected randomly and injected defibrase by intravenous injection and abdominocentesis. Plasma FIB was measured before and after injection 1,3,6,12,24h by intravenous haemospasia. ResultsPlasma FIB was significantly reduced in intravenous treatment group, and it was lowerest in 3h after intravenous treatment.Clinical Neurological Deficits Scale and infarction volume was significantly reduced in intravenous treatment group than saline control group and coeliac treatment group.There was improvement in Clinical Neurological Deficits Scale in coeliac treatment group compared with that of saline control group, but there was no statistically significant differences at infarction volume.Clinical Neurological Deficits Scale and infarction volume was statistically significant differences in intravenous treatment group at 0.5,3 hours after MCAO. There were no statistically significant differences in intravenous treatment group at 6, 9,12 hours after MCAO.Conclusions Defibrase can reduce the infarction volume in cerebral ischemia early stage.

Experimental study on the therapeutic effectiveness of defibrase in rat focal cerebral ischemia reperfusion model / 中国康复理论与实践

@#ObjectiveTo investigate the therapeutic effectiveness of defibrase in treating penumbra and reperfusion.MethodsIntraluminal suture method was used to develope reversible middle cerebral artery occlusion(MCAO). Rats were subjected to MCAO 3 hours followed by reperfusion for 3, 6, 24, 72 hours, and to MCAO 6 hours followed by reperfusion for 3, 6, 24 hours. The treatment groups rats were injected intravenously defibrase at 0.5 hour before reperfusion. Meanwhile, the control group received normal saline. Clinically Neurological Deficits Scale were evaluated every day. Infarction volume was measured by using 2,3,5-triphenyltetrazolium chloride staining. Pathologic change were examined microscopically in HE stained sections.ResultsThere were significant difference at treatment groups of reperfusion 3 hours after MCAO.Infarction volume and Clinically Neurological Deficits Scale was significant reduced as control group (P<0.05). There were no significant differences at treatment groups of reperfusion 6 hours after MCAO (P>0.05). Cerebral hemorrhage wasn't increased in defibrase treatment group.ConclusionsDefibrase was effective on Clinically Neurological Deficits of rats in reperfusion 3 hours after MCAO.

Effect of Blood Glucose Level on Infarct Volume in Transient Cerebral Ischemia in Rats

In order to find out the effect of blood glucose on the ischemic brain injury, the authors studied the relationship between the blood glucose level and the infarct volume in a focal cerebral ischemia-reperfusion model in a series of 60 adult rats. The experimental animals were divided into 4 groups of 15 rats: rats in group I were allowed free access to food until ischemic insults: rats in group II were fasted for 24 hours prior to ischemic insult: rats in group III were fed but received intraperitoneal injection of 1.7unit/kg of insulin 50 minutes before the onset of ischemia: and rats in group IV were fed and received intraperitoneal injection of 2g/kg of 50% glucose during ischemia. The ischemia was made through unilateral occlusion of the middle cerebral artery(MCA) by inserting a 16mm length of 4-0 nylon surgical thread through the internal carotid artery as well as occlusion of both common carotid arteries(CCA) using nontraumatic aneurysm clips. Reperfusion was induced by pulling the thread that occluded the MCA as well as removing the aneurysm clips from both of the CCAs. Each group was further divided into a(2 hour), b(4 hour), and c(6 hour) subgroups of 5 rats according to the duration of ischemia. All animal were killed 3 hours after reperfusion, and infarct volume determined by triphenyltetrazolium chloride was calculated by a computer image software. The results showed that rats of glucose loaded during ischemia(group IV) developed the highest blood glucose levels during ischemia and post-ischemia and the largest infarct volume among groups. The rats which were fed until ischemic insult(group I) developed higher blood glucose levels and larger infarct volume than those developed in group II and III. The rats of group III developed higher blood glucose levels and larger infarct volume than group II. According to our data, lowering the blood glucose level by fasting or intraperitoneal injection of insulin reduced the infarct volme in model of transient focal cerebral ischemia. These results suggest that maintenance of low level of blood glucose during early phase of cerebral infarction may reduce volume of infarction and neurological sequelae.