Compressive Mechanical Properties and Constitutive Model of Brain Tissues / 医用生物力学

Objective To study the compressive mechanical properties and constitutive models of brain tissue at different strain rates.Methods Quasi-static and medium-velocity compression tests were carried out on the white and gray matter of pig brain tissue using an electronic universal testing machine,and stress-strain curves of pig brain tissue at different strain rates were obtained.The Ogden constitutive model was used to fit the test curve,the parameters of the constitutive model were determined,and the simulation was verified using finite element software.Results The brain tissue stress-strain curves showed nonlinear characteristics,with a strong strain rate correlation and sensitivity.When tissues were compressed to 0.6 strain,the stress of white and gray matter increased by 102%and 129%,respectively,at a strain rate of 5×10-4-5×10-2 s-1,and by 50.7%and 54.6%,respectively,at a strain rate of 1-1.5 s-1.At a strain rate of 1.5 s-1,the stress in the white and gray matter increased by 347%and 413%,respectively,compared with that at 5×10-4 s-1 strain rate.The R2 value of the Ogden model was greater than 0.99,and the error between the simulation and experimental results was within 15%,thereby verifying the validity of the model.Conclusions This study is helpful for the prediction of brain tissue deformation and provides an accurate scientific theoretical basis for the establishment of scientific and reasonable human simulation targets as well as the design and improvement of brain-protective equipment.

Effects of gestational diabetes mellitus on brain development and miRNAs expression profile in neonatal mice / 中国儿童保健杂志

【Objective】 To study the effects of gestational diabetes (GDM) on morphological structure of brain tissue and microribonucleotide (miRNA) expression profile in neonatal mice, and to provide a new research target for the prevention and treatment of abnormal neurodevelopment in GDM progeny. 【Methods】 The pregnant mice were divided into model group and control group,each group consisted of 10 mice. The model group mice established a GDM model by injecting streptozotocin to measure fasting blood glucose (FPG) and random blood glucose (GLU) at different times. Successful molded mice were randomly divided into model group A and model group C, and control mice were divided into control group B and control group D, with 5 mice in each group. The newborn mice in groups A and B were used for hippocampal tissue GeneChip detection and brain morphology structure observation, and group C and D newborn mice were used for qRT-PCR detection of hippocampus tissue expression differences to verify the differentially expressed genes of miRANs obtained by GeneChip screening. After giving birth, the neonatal mice were sacrificed by decapitation, and the brain tissue was dissected to observe the overall morphological structure. The structural changes of hippocampus were observed under HE chromogenic microscope. The Agilent mouse miRNA oligonucleotide gene chip was used to detect the miRNA expression profile of mouse hippocampus, screen differential miRNAs and predict their target genes, and conduct GO analysis and signal transduction pathway analysis of target genes. The relative expression levels of the screened miRNAs were verified by qRT-PCR. 【Results】 Compared with the control group, the GLU increased significantly from the 3rd day after drug administration in the model group (P<0.01). Macroscopic observation of control group B mice had normal brain morphology and structure, smooth appearance, clear gyrus, close arrangement of hippocampus cell structure, uniform staining and complete structure; in model group A, the number of hippocampus cells decreased, loose arrangement and deep staining. In the initial screen of miRNA microarray, there were 11 differentially expressed miRNAs between control and model groups, all of which were downregulated miRNAs, including let-7b-5p、miR-130b-3p、miR-181c-5p、miR-181d-5p、miR-3099-3p、miR-3470a、miR-3473a、miR-3473b、miR-500-3p、miR-532-5p、miR-7047-5p(P<0.05). Two miRNAs (miR-3473b, miR-7047-75p) and 5 target genes (MAPK3, MAPK11, MAPK14, CALM3, AKT3). The relative expression of miR-3473b and miR-7047-5p in model group C were lower than that in control group D (t=19.13 and 6.24, P<0.05), and the validation results were consistent with the microarray test results. 【Conclusion】 Compared with the offspring of normal pregnant mice, GDM offspring mice have abnormal development of brain structure and damage of hippocampal nerve cells, and there are a large number of abnormal expression of miRNAs in hippocampal tissue. Differentially expressed miRNAs can be used as research targets for prevention and treatment of GDM offspring neurodevelopmental abnormalities.

Establishment and evaluation of a streptozotocin-induced diabetic encephalopathy rat model / 中国组织工程研究

BACKGROUND:Animal models of diabetic encephalopathy that have been studied mainly include streptozotocin-induced model,high-sugar and high-fat diet-induced model and spontaneous animal model.Establishing a simple,easy,short-cycle,safe and effective model of diabetic encephalopathy can help to explore the subsequent pathogenesis and screen therapeutic drugs. OBJECTIVE:To further explore and evaluate the method of building diabetic encephalopathy rat models. METHODS:Twenty Sprague-Dawley rats were randomly divided into control(n=10)and model(n=10)groups.Rats in the model group were given a single injection of 45 mg/kg streptozotocin in the left lower abdominal cavity,and those in the control group were given the same amount of citrate buffer.During the experiment,the body mass,feed intake,water intake and blood glucose were measured.After 8 weeks,the glucose tolerance and oxidative stress levels were measured,and the pathological changes of brain tissue and the expression of apoptotic proteins were compared between groups. RESULTS AND CONCLUSION:Compared with the control group,the food intake,water intake,encephalization quotient,blood glucose and area under the blood glucose curve were significantly increased in the model group,while the body mass decreased significantly(P<0.01).Histopathological examination of the brain showed that compared with the control group,the number of surviving nerve cells was significantly reduced in the model group(P<0.01),with more significant pathological damage of nerve cells.Compared with the control group,the activities of serum superoxide dismutase,catalase and glutathione in the model group were significantly decreased(P<0.01),and the content of oxidative malondialdehyde was significantly increased(P<0.05).The expression levels of apoptosis-related proteins Bax and Caspase-3 in brain tissue increased in the model group compared with the control group,while the expression of Bcl-2 decreased(P<0.01).In conclusion,an 8-week injection of 45 mg/kg streptozotocin can cause obvious pathological damage to the brain tissue of diabetic rats,to successfully establish the rat model of diabetic encephalopathy.

Sequencing,verification and functional analysis of differentially expressed genes in brain tissue of a rat model with acute intracerebral hemorrhage / 中国组织工程研究

BACKGROUND:There are differentially expressed genes in acute intracerebral hemorrhage,which are related to the occurrence and development of intracerebral hemorrhage. OBJECTIVE:To screen differentially expressed genes and key genes in brain tissue of a rat model with acute intracerebral hemorrhage,to validate them through qPCR,and to analyze the relationships between key genes and the neurological function and brain tissue water content after intracerebral hemorrhage. METHODS:Seventy-eight Sprague-Dawley rats were randomly divided into two groups:in intracerebral hemorrhage group,a rat model of acute intracerebral hemorrhage was made using collagenase injection at the right caudate nucleus;and in sham-operated group,rats were injected with equal amount of saline at the same site.RNA was extracted from rat brain tissues of both groups using the TRIzol method and transcriptome sequencing technology was used to identify differentially expressed genes in brain tissues of acute intracerebral hemorrhage,which were then verified by qPCR and analyzed for the relationships between the genes and neurological function and brain tissue water content after intracerebral hemorrhage.And the key genes were analyzed by GO and KEGG functional enrichment analysis in combination with bioinformatics. RESULTS AND CONCLUSION:Ten key genes were identified,including CXCL8,SERPINE1,TFPI2,CXCR4,GDA,KCNQ5,ERICH3,SCN3B,CACNA1E,and CCL20.The contents of GDA,KCNQ5,ERICH3,SCN3B,and CACNA1E in the intracerebral hemorrhage group were lower than those in the sham-operated group(P＜0.05).The contents of CXCL8,SERPINE1,TFPI2,CXCR4 and CCL20 in the intracerebral hemorrhage group were higher than those in the sham-operated group(P＜0.05).The contents of GDA,KCNQ5,ERICH3,SCN3B,and CACNA1E were positively correlated with brain tissue water content and neurologic deficit score(P＜0.05),while the contents of CXCL8,SERPINE1,TFPI2,CXCR4 and CCL20 were negatively correlated with brain tissue water content and neurologic deficit score(P＜0.05).GO analysis indicated that differentially expressed genes were mainly enriched in two biological processes(leukocyte chemotaxis and chemokine-mediated signaling pathways),two cell components(cation channel complexes and ion channel complexes),and two molecular functions(gated channel activity and ion channel activity).KEGG analysis indicated that differentially expressed genes were concentrated in tumor necrosis factor signaling pathway,glutamatergic synapses and GABAergic synapses.To conclude,the differentially expressed genes in intracerebral hemorrhage include CXCL8,SERPINE1,TFPI2,CXCR4,GDA,KCNQ5,ERICH3,SCN3B,CACNA1E,and CCL20,and these genes are related to brain tissue water content and neurological function after intracerebral hemorrhage.These genes are mainly enriched in cell components,binding functions,cellular protrusions,and other related biological functions.

Preliminary observation on the development and dynamic changes of chronic toxoplasmosis in mice / 中国血吸虫病防治杂志

Objective To investigate the development and dynamic changes of cysts in the brain of mice following infection with different forms of Toxoplasma gondii, so as to provide insights into for toxoplasmosis prevention and control. Methods ICR mice at ages of 6 to 8 weeks, each weighing 20 to 25 g, were intraperitoneally injected with tachyzoites of the T. gondii PRU strain at a dose of 1 × 105 tachyzoites per mouse, orally administered with cysts at a dose of 20 oocysts per mouse or oocysts at a dose of 200 oocysts per mouse for modeling chronic T. gondii infection in mice, and the clinical symptoms and survival of mice were observed post-infection. Mice were orally infected with T. gondii cysts at doses of 10 (low-dose group), 20 (medium-dose group), 40 cysts per mouse (high-dose group), and the effect of different doses of T. gondii infections on the number of cysts was examined in the mouse brain. Mice were orally administered with T. gondii cysts at a dose of 20 cysts per mouse, and grouped according to gender (female and male) and time points of infections (20, 30, 60, 90, 120, 150, 180 days post-infection), and the effects of gender and time points of infections on the number of cysts was examined in the mouse brain. In addition, mice were divided into the tachyzoite group (Group T), the first-generation cyst group (Group C1), the second-generation cyst group (Group C2), the third-generation cyst (Group C3) and the fourth-generation cyst group (Group C4). Mice in the Group T were intraperitoneally injected with T. gondii tachyzoites at a dose of 1 × 105 tachyzoites per mouse, and the cysts were collected from the mouse brain tissues 30 days post-infection, while mice in the Group C1 were orally infected with the collected cysts at a dose of 30 cysts per mouse. Continuous passage was performed by oral administration with cysts produced by the previous generation in mice, and the effect of continuous passage on the number of cysts was examined in the mouse brain. Results Following infection with T. gondii tachyzoites, cysts and oocysts in mice, obvious clinical symptoms were observed on days 6 to 13 and mice frequently died on days 7 to 12. The survival rates of mice were 67.0%, 87.0% and 53.0%, and the mean numbers of cysts were (516.0 ± 257.2), (1 203.0 ± 502.0) and (581.0 ± 183.1) in the mouse brain (F = 11.94, P < 0.01) on day 30 post-infection with T. gondii tachyzoites, cysts and oocysts, respectively, and the numbers of cysts in the brain tissues were significantly lower in mice infected with T. gondii tachyzoites and oocysts than in those infected with cysts (all P values < 0.01). The survival rates of mice were 87.0%, 87.0% and 60.0%, and the mean numbers of cysts were (953.0 ± 355.5), (1 084.0 ± 474.3) and (1 113.0 ± 546.0) in the mouse brain in the low-, medium- and high-dose groups on day 30 post-infection, respectively (F = 0.42, P > 0.05). The survival rates of male and female mice were 73.0% and 80.0%, and the mean numbers of cysts were (946.4 ± 411.4) and (932.1 ± 322.4) in the brain tissues of male and female mice, respectively (F = 1.63, P > 0.05). Following continuous passage, the mean numbers of cysts were (516.0 ± 257.2), (1 203.0 ± 502.0), (896.8 ± 332.3), (782.5 ± 423.9) and (829.2 ± 306.0) in the brain tissues of mice in the T, C1, C2, C3 and C4 groups, respectively (F = 4.82, P < 0.01), and the number of cysts was higher in the mouse brain in Group 1 than in Group T (P < 0.01). Following oral administration of 20 T. gondii cysts in mice, cysts were found in the moues brain for the first time on day 20 post-infection, and the number of cysts gradually increased over time, peaked on days 30 and 90 post-infection and then gradually decreased; however, the cysts were still found in the mouse brain on day 180 post-infection. Conclusions There is a higher possibility of developing chronic T. gondii infection in mice following infection with cysts than with oocysts or tachyzoites and the most severe chronic infection is seen following infection with cysts. The number of cysts does not correlate with the severity of chronic T. gondii infection, and the number of cysts peaks in the mouse brain on days 30 and 90 post-infection.

Expression of protein phosphatase 4 in different tissues under hypoxia

Relevant research data shows that there is a certain degree of energy metabolism imbalance in highland residents. Protein phosphatase 4 (PP4) has been found as a new factor in the regulation of sugar and lipid metabolism. Here, we investigate the differential expression of PP4 at a simulated altitude of 4,500 m in the heart, lung, and brain tissues of rats. A hypoxic plateau rat model was established using an animal decompression chamber. A blood routine test was performed by an animal blood cell analyzer on rats cultured for different hypoxia periods at 4,500 m above sea level. Quantitative polymerase chain reaction (qPCR) and western blot were used to detect the changes of protein phosphatase 4 catalytic subunit (PP4C) gene and protein in heart, lung, and brain tissues. The PP4C gene with the highest expression level found in rats slowly entering the high altitude area (20 m-2200 m-7 d-4500 m-3 d) was about twice as high as the low elevation group (20 m above sea level). The simulated high-altitude hypoxia induced an increase of PP4C expression level in all tissues, and the expression in the lung tissue was twice as expressed as heart and brain tissue at high altitude (P < 0.05). These results suggest that the PP4 phosphatase complex is ubiquitously expressed in rat tissues and likely involved in adaptation to or disease associated with high-altitude hypoxia.

Changes of RAGE/p38MAPK/NF-κB signaling pathway in brain tissue of subchronic fluorosis rats and protective effects of Ginkgo biloba extract and RAGE antagonist / 环境与职业医学

Background Fluorine accumulates in the brain tissue after long-term excessive intake and subsequently cause nerve damage and decline of learning and memory ability. Receptor of advanced glycation end-products (RAGE)/p38 mitogen-activated protein kinase (p38MAPK)/nuclear factor kappa-B (NF-κB) signaling pathway is considered to be involved in the associated mechanism. Objective To study the changes of RAGE/ p38MAPK/ NF-κB signaling pathway in rats with subchronic fluorosis, and to explore the protective effects of extract of Ginkgo biloba 761 (EGb761) and RAGE antagonist (FPS-ZM1) on neuromemory ability. Methods Ninety male clean SD rats were divided into 9 groups with 10 rats in each group. The modeling period was 6 months. Control group (C group): free drinking tap water (fluoride content <0.5 mg·L−1), low- and high-dose fluoride groups (LF group, HF group): free drinking tap water with 10 or 50 mg·L−1 fluoride; intervention group of Ginkgo biloba extract (CE, LFE, and HFE groups): on the basis of the C group, LF group, and HF group, 100 mg·kg−1·d−1 EGb761 was given daily via intragastric administration; FPS-ZM1 intervention groups (CF, LFF, and HFF groups): 7 d before the end of modeling, 1 mg·kg−1·d−1 FPS-ZM1 was injected intraperitoneally daily on the basis of the C group, LF group, and HF group. The contents of fluoride in brain and blood of each group were detected. The learning and memory ability was tested by water maze experiment. The histopathologic changes of the hippocampus were detected by Nissl staining. The protein expression levels of RAGE and its ligand high mobility group protein B1 (HMGB1), NF-κB, p38MAPK, phospho-p38MAPK (p-p38MAPK), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α) in brain tissue were detected by Western blotting. The mRNA expression levels of RAGE, HMGB1, and p38MAPK were detected by quantitative real-time PCR. Results Compared with the C group, the contents of blood fluoride and brain fluoride in the LF and the HF groups were increased (P<0.05). The results of the water maze experiment showed that, compared with the C group, the escape latency time of the LF group and the HF group was longer and the crossing times were reduced; compared with the HF group, the escape latency time of the HFE group and the HFF group was shortened, and the crossing times were increased (P<0.05). The Nissl staining results showed that the number of Nissl body in the HF group decreased compared with the C group; compared with the HF group, the number of Nissl body in the HFE group and the HFF group increased. The Western blotting results showed that compared with the relative protein expression levels of RAGE, HMGB1, NF-κB, p38MAPK, p-p38MAPK, IL-6, and TNF-α in the C group , the levels of above indicators in the HF group and the levels of RAGE, HMGB1, NF-κB, p-p38MAPK, and IL-6 in the LF group were up-regulated (P<0.05); compared with the HF group, the levels of above indicators in the HFE group and the HFF group were all down-regulated (P<0.05); compared with the relative protein expression levels of RAGE and HMGB1 in the LF group, the levels in the LFE group and the LFF group were all down-regulated (P<0.05). The quantitative real-time PCR results showed that compared with the C group, the mRNA expression levels of RAGE and HMGB1 in the LF group and the HF group were up-regulated; compared with the LF group, the mRNA expression levels of RAGE in the LFE group and the LFF group were down-regulated ; compared with the HF group, the mRNA expression levels of RAGE and HMGB1 in the HFE group and the HFF group were down-regulated (P<0.05). Conclusion The central nervous system injury caused by subchronic fluorosis may be related to the activation of RAGE/p38-MAPK/NF-κB signaling pathway, which can impair the learning and memory ability of rats, while EGb761 and FPS-ZM1 may have certain protective effects on the nerve injury.

Dynamic pathological changes of Toxoplasma cysts in mouse brain during chronic infection / 安徽医科大学学报

Objective@#To investigate the distribution of toxoplasma cysts in the brain of infected mice and the effect of pathological changes on the behavior and neuropsychiatry of the mice during chronic infection with Toxoplasma gondii( T．gondii) ．@*Methods @#Mice were infected with Prugniaud strain of T．gondii by oral gavage．The brain tissues of infected mice were collected on the days of 10，30，40，90，120 and 160 after infection respectively，and the hippocampal hypothalamus，prefrontal lobe ，striatum and cerebellum regions were separated．The number of cysts and neuropathological changes in each infected area were observed and recorded by HE staining．The number of cysts and neuropathological changes in each infected area were observed and recorded. @*Results @#T．gondii infected mice showed symptoms of vertical hair and arched back，which were the most significant on the 40th day，and then gradually recovered with hemiplegia and circling in circles． At each time point ，the number of toxoplasma cysts was the largest in hippocampal hypothalamus，followed by prefrontal lobe and striatum，and the least in cerebellum．The diameter of toxoplasma cysts increased with time．During chronic infection，specific pathological manifestations of toxoplasma encephalitis，such as neuronophagy，were observed in all regions of the brain tissue．The above pathological changes of toxoplasma encephalitis reached the peak on the 40th day，and gradually recovered， and increased to the stimulation peak on the 120th day，and then gradually recovered．@*Conclusion@# The behavioral and neuropsychiatric symptoms of T．gondii during chronic infection were correlated with the localization and distribution of toxoplasma cysts in the brain of infected mice，and showed dynamic changes.

Effect of trimethyltin chloride on brain metabolism detected by PET-CT / 中国职业医学

{L-End}Objective To explore the feasibility of using positron emission tomography (PET) -computed tomography (CT) to detect brain metabolic abnormalities caused by trimethyltin chloride (TMT) poisoning. {L-End}Methods Specific pathogen free healthy SD rats were randomly divided into model group and control group with six rats in each group. Rats in the model group were intraperitoneally injected with a single dose of 10 mg/kg body mass of TMT solution, and rats in the control group were intraperitoneally injected with a single dose of an equal volume of 0.9% sodium chloride solution. Rats were anaesthetized after three days of modeling and underwent PET-CT brain scanning to detect the standardized uptake value (SUV) of 18F-2-fluro-D-deoxy-glucose (18F-FDG). After scanning, rats were sacrificed and brain tissues were collected for brain organ coefficients calculation and brain histopathological analysis. {L-End}Results The rats in the model group showed symptoms of head tremor, limb twitching, irritability and others after TMT modeling. There was no significant difference in the body mass between the two groups of rats on the third day of modeling (P>0.05). The 18F-FDG uptake in the cerebral cortex, cerebellum and brainstem of the rats in the model group was significantly weakened compared with the control group, with deceased SUV values (all P<0.05). No obvious abnormalities were found in CT images and freshly collected brain tissues of rats of the control and model groups. The brain organ coefficients of rats in the two groups showed no significant difference (P>0.05). The results of hematoxylin-eosin staining of brain tissue showed that the cerebral cortex of rats in the model group had more tiny cavities than that of the control group, and some neuronal cells and a small number of hippocampal vertebral cells were tightly and deeply stained, with the cytoplasm and nucleus poorly demarcated, and pericellular space enlarged. The results of Nissen staining showed that the arrangement of neuronal cells in the model group was slightly disordered, and the interstitial space was slightly enlarged, but no other significant abnormal changes were observed. {L-End}Conclusion PET-CT can be used in detecting the metabolic abnormalities of brain in TMT poisoning rat model, making it a sensitive detection method for TMT poisoning.

Expression and localization of neuroglobin in the brain tissue of Saiga antelope / 解剖学报

Objective Saiga antelope is a small population inhabiting in desert and semi desert areas of national and world endangered protected animals, its wild population is extremely rare. In order to explore the correlation between hypoxic tolerance and neuroglobin (NGB) in Saiga antelope. A female Saiga antelope died of dystocia was used as the experimental animal, and the tissue samples were sampled repeatedly for 3 times to study the distribution and expression of NGB in brain of Saiga antelope in the process of adapting to hypoxia. Methods The distribution and expression of NGB in the parietal lobe, frontal lobe, temporal lobe, occipital lobe, hypothalamus, hippocampus, pear like leaf, cingulate gyrus, striatum and thalamus of Saiga antelope were detected by immunohistochemistry(IHC) and Real-time PCR. Results The result of IHC showed that NGB was positive in all parts of Saiga antelope brain, and the cells that had positive reactions in the parietal, frontal, temporal and occipital lobes of the cerebral cortex were mostly granular cells and martinotti cells. NGB was found in the granular cell layer, pyramidal cell layer and molecular cell layer in hippocampus, and the positive staining of pyramidal cell layer was the strongest. NGB positive expression in Pear like leaves and hypothalamus mainly occured in multi-type cells. NGB was expressed in the granulocytes and glial cells of cingulate gyrus, mainly in the granular cells. The positive expression of NGB in striatum was mainly located in granular cells, the positive expression of NGB in thalamus could be seen in the polymorphosis and glial cells, and the positive substance of the multi-type cells was obviously colored. The result of Real-time PCR showed that NGB was expressed in different regions of Saiga antelope brain, the highest expression in the frontal lobe of the cerebral cortex, the second in the parietal lobe, and the expression was significantly higher than that in the rest of the brain tissue (P0.05). Conclusion The expression of NGB in different regions of Saiga antelope has some selective differences in the long-term adaptation to hypoxia environment. The frontal and parietal lobes have the highest tolerance to hypoxia, followed by hippocampus, and the striatum is the weakest, which may be related to the specific functions of different regions of brain tissue, but the specific mechanism remains to be further explored.

Brain banking in India: Relevance in current day practice

Biobanks are set to become the norm. The explosion of new and powerful technologies like genomics and other multiomics has catapulted research from individual laboratories to multi-institutional and international partners. Today, with increasing life span, and the rising incidence of brain diseases, Brain Banks have become an invaluable source for unravelling the pathogenesis of several brain disorders, and develop effective therapies. The article briefly reviews the evolution of brain banking, rise of global networks, with a brief overview of steps involved from donor recruitment, protocols of processing, storage, annotation, and tissue distribution. The ethics of biobanking is one of the most controversial issues in bioethics, the key issues being consent, confidentiality, and commercialisation. Regulatory authorities in different countries and in India, the Indian Council of Medical Research has taken a lead to formulate new ethical guidelines for research involving human participants protecting rights, and well-being of research participants. Although brain banks have been established in the 1960s, in India, the first Brain Bank was established in 1995 at the National Institute of Mental Health and Neurosciences, Bengaluru. Now a network with two more Brain banks is being established in the country. The challenges and benefits of establishing the first Brain Bank as a National Research Facility in India is shared. For optimising available resources and promote brain banking, it is essential for medical professionals, and the public to perceive the crucial advantage in conversion of biological waste into invaluable resources for neuroscience. This will be the greatest “gift of hope” that we can offer for the future generations to overcome hitherto untreatable disorders such as dementias.

Effect of chest compression synchronized ventilation on cerebral oxygenation in a porcine cardiopulmonary resuscitation model / 中华急诊医学杂志

Objective:To investigate the effect of chest compression synchronized ventilation on cerebral oxygenation in porcine cardiopulmonary resuscitation model.Methods:The porcine ventricular fibrillation model was constructed and randomly(random number)divided into two groups by envelope method. According to the different modes of ventilator during cardiopulmonary resuscitation, they were named intermittent positive pressure ventilation (IPPV) group and chest compression synchronized ventilation (CCSV) group. The arterial blood lactic acid value at 4 and 7 min after resuscitation and 30 min after spontaneous circulation recovery , carotid blood flow (CBF) within 1-8 min during resuscitation, cerebral oxygen saturation at 1 , 2 , 3, and 4 h after resuscitation were recorded. Neurological score was assessed 24 h after resuscitation.Results:The lactic acid value at 3 time points in the CCSV group was significantly lower than that in the IPPV group; during the resuscitation, the CBF of the pig carotid artery in the CCSV group was significantly higher than that in the IPPV group within 1-8 min during resuscitation; cerebral oxygen saturation was also significantly higher in the IPPV group at all time points after resuscitation. The neurological score of the CCSV group decreased significantly 24 h after resuscitation.Conclusions:The choice of CCSV ventilation mode in porcine ventricular fibrillation model can significantly improve cerebral perfusion during cardiac arrest and cerebral oxygenation after resuscitation.

Identification of Down syndrome fetal encephalopathy related genes and signaling pathways via bioinformatics analysis / 中华实用儿科临床杂志

Objective:To identify Down syndrome (DS) fetal encephalopathy related genes and signaling pathways via bioinformatics analysis, and to explore their potential mechanisms underlying the occurrence and development of DS neuropathology.Methods:Retrospective study.In December 2021, dataset GSE59630 was downloaded from the gene expression omnibus (GEO), and differentially expressed genes (DEGs) between DS and normal fetal brain tissue were identified by R software.Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and gene set enrichment analysis (GSEA) were performed on the genes identified.The protein-protein interaction (PPI) network was constructed based on search tool for the retrieval of interacting genes online database and Cytoscape software, and key modules and hub DEGs were identified.Real-time quantitative polymerase chain reaction technique was used to verify the expression of hub genes related to neurodegeneration in brain tissue of 3 pairs of DS and normal fetuses at the gestational age of 22-33 weeks.Results:A total of 225 DEGs were screened out from DS and normal fetal brain tissue, including 18 up-regulated genes and 207 down-regulated genes.GO functional enrichment analysis showed that DEGs were mainly enriched in neurogenesis, neuronal apoptosis, transcriptional regulation, mitochondrial energy metabolism, etc.KEGG pathway enrichment analysis revealed that DEGs were associated with a variety of neurodegenerative diseases.GSEA suggested that apoptosis and inflammatory responses play a vital part in the occurrence of DS neuropathology.Ten hub genes were identified by the PPI network established, and they were mainly related to histone acetylation and transcriptional regulation.According to the tissue verification result, the variations of RAB8A, TBP and TAF6 expression conformed to the microarray data. Conclusions:The key genes and signaling pathways identified by transcriptome analysis of fetal brain tissue facilitate the comprehensive understanding of the molecular mechanism of DS neuropathology.This study provides a novel insight into the clinical diagnosis and treatment of neurodevelopmental abnormalities and mental retardation in DS.

Continuous monitoring of intracranial pressure and partial oxygen pressure of brain tissue in patients with severe traumatic brain injury after standard decompressive craniectomy and microscopic hematoma removal / 中国综合临床

Objective:To investigate the effect of continuous intracranial pressure (ICP) and brain oxygen partial pressure (PbtO 2) monitoring and guiding treatment after the application of standard large bone flap decompression and microhematoma removal in patients with severe traumatic brain injury (TBI). Methods:A retrospective analysis was done of 41 patients with TBI in Department of Neurosurgery in the Inner Mongolia People's Hospital from January 2018 to May 2020. Patients with Glasgow coma scale (GCS)<8 points were treatesd with microscopical removal of hematoma and contusion brain tissue and standard large bone flap decompression. Intraoperative intracranial pressure and brain tissue oxygen partial pressure monitoring probes were placed. Postoperatively, continuous intracranial pressure monitoring and partial oxygen pressure monitoring of brain tissue were performed, and target-based treatment under ICP and PbtO 2 monitoring was performed. According to the Glasgow Outcome (GOS) score after six months, patients were divided into a good outcome group (4-5 scores) and a poor outcome group (1-3 scores). There were 26 cases in good prognosis group and 15 cases in poor prognosis group. Linear regression analysis was used to further evaluate the relationship between PbtO 2, ICP and GOS score. The measurement data of normal distribution were compared by independent sample t-test. The counting data were expressed in cases (%), and the comparison between groups was adopted χ 2 inspection. The general linear bivariate Pearson correlation test was used. Results:The mean value of PbtO 2 (17.42±5.34) mmHg in the poor prognosis group was lower than that in the good prognosis group (24.65±5.61) mmHg, with statistical significance ( t=4.04, P<0.001). The mean value of ICP (22.32±3.45) mmHg in the poor prognosis group was higher than that (17.32±3.23) mmHg in the good prognosis group, with statistical significance ( t=4.15, P<0.001). Using PbtO 2 and ICP as independent variables and GOS score after 6 months as dependent variable, a regression equation was established ( Y=4.040 X+7.497; Y=-2.549 X+28.63). The mean value of PbtO 2 was positively correlated with GOS scores after 6 months in patients with severe head injury ( r=0.75, P<0.001). The mean value of ICP was negatively correlated with the prognosis of patients with severe head injury ( r=-0.87, P<0.001). Conclusion:The treatment guided by ICP combined with PbtO 2 monitoring is valuable in improving the prognosis of patients with severe traumatic brain injury after standard decompressive craniectomy, and may improve the prognosis 6 months after the injury.

Pharmacokinetic behavior and brain tissue distribution of paeoniflorin combined with normal and toxic doses of strychnine in rats after percutaneous administration / 中国中药杂志

This study aims to establish a rapid and sensitive UPLC-MS/MS method for simultaneously determining the content of strychnine and paeoniflorin in plasma and brain tissue of rats, and compare the pharmacokinetic behavior and brain tissue distribution of paeoniflorin combined with normal and toxic doses of strychnine in rats after percutaneous administration. Compared with those in the toxic-dose strychnine group, the AUC_(0-t), AUC_(0-∞), and C_(max) of strychnine decreased by 51.51%, 45.68%, and 46.03%, respectively(P<0.01), and the corresponding values of paeoniflorin increased by 91.41%, 102.31%, and 169.32%, respectively(P<0.01), in the compatibility group. Compared with the normal-dose strychnine group, the compatibility group showed insignificantly decreased C_(max), AUC_(0-t), and AUC_(0-∞) of strychnine, increased C_(max) and T_(max) of paeoniflorin(P<0.01), 66.88% increase in AUC_(0-t), and 70.55% increase in AUC_(0-∞) of paeoniflorin. In addition, the brain tissue concentration of strychnine decreased and that of paeoniflorin increased after compatibility. The combination of paeoniflorin with normal dose and toxic dose of strychnine can inhibit the percutaneous absorption of strychnine, and greatly promote the percutaneous penetration of paeoniflorin, whereas the interaction mechanism remains to be explored. The UPLC-MS/MS method established in this study is easy to operate and has good precision. It is suitable for in vivo study of pharmacokinetic behavior and brain tissue distribution of paeoniflorin and strychnine after percutaneous administration in rats, which provides reference for the safe and rational clinical use of strychnine and the combined use of drugs, and lays a solid foundation for the development of external preparations containing Strychni Semen.

Effect of Chloriti Lapis on Metal Elements in Brain and Plasma of PTZ-kindled Epileptic Rats / 中国实验方剂学杂志

Objective:To investigate the effect of Chloriti Lapis on metal elements in brain tissue and plasma of epileptic rats kindled by pentylenetetrazol （PTZ）， and to explore the possible material basis of Chloriti Lapis. Method:PTZ kindling method was used to establish epileptic rat model. Inductively coupled plasma mass spectrometry （ICP-MS） and inductively coupled plasma optical emission spectrometer （ICP-OES） were used to determine the contents of metal elements in brain tissue and plasma of the blank group， model group， carbamazepine group （0.1 g·kg^-1） and Chloriti Lapis group （2 g·kg^-1）. The data were statistically analyzed by SPSS 18.0 software. Result:Compared with the blank group， the contents of Sr， Sb and Ba in brain tissue of rats in the model group were significantly increased （<italic>P</italic><0.05， <italic>P</italic><0.01）， while the contents of Zn， Fe， Cu， K， Li， Co， Sn and Pb were significantly decreased （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the model group， the contents of Zn， Fe， K， Li， Co， As and Pb in brain tissue of rats in the Chloriti Lapis group were obviously increased （<italic>P</italic><0.05， <italic>P</italic><0.01）， while the contents of Sr and Sb were significantly decreased （<italic>P</italic><0.01）. These results showed that Chloriti Lapis had positive effect on the regulation of the content of metal elements in rat brain tissue to normal level， the intervention effect was clear， and the overall effect was better than that of carbamazepine group. The determination of 21 metal elements in plasma showed that compared with the blank group， the levels of K， Sr and Cd in the model group were significantly increased （<italic>P</italic><0.05）， and the contents of Li， Al， Ti and Cr were significantly decreased （<italic>P</italic><0.05）. Compared with the model group， the contents of Ca， K， Li， Al and V in the Chloriti Lapis group were obviously increased （<italic>P</italic><0.05， <italic>P</italic><0.01）， and the contents of Fe， Ti， Sr and Cd were significantly decreased （<italic>P</italic><0.05，<italic>P</italic><0.01）. The correlation analysis of metal elements among the groups showed that there were 17 pairs of elements had positively correlation in the brain tissue of rats， 2 pairs of elements had significant negative correlation. In the plasma of rats， 8 pairs of elements had significant positive correlation and 6 pairs of elements had significant negative correlation. Conclusion:The metal element groups represented by Zn， Fe， K， Li， Co， As， Pb， Sr， Sb， Ca， Al， V， Ti and Cd may be the effective material basis for Chloriti Lapis to interfere PTZ-kindled epileptic model rats， which may be related to the influence of these metal element groups on the release of neurotransmitters and the electrical balance of neurons， the regulation of abnormal synchronous discharge induced by Na⁺， K⁺， Ca²⁺ channel disorders and intervention of metabolism pathways in brain tissue related to epilepsy. It can make the excitatory and inhibitory activities restrain each other， and finally reach the normal physiological state of neurons and cells. The intervention effect of Chloriti Lapis group was better than that of carbamazepine group.

Metabolomics Analysis of Chloriti Lapis on Brain Tissue of PTZ-kindled Epileptic Rats / 中国实验方剂学杂志

Objective:To explore the possible mechanism of Chloriti Lapis in the treatment of epilepsy by the metabonomics of brain tissue in pentylenetetrazol （PTZ）-kindled epileptic rats treated with Chloriti Lapis. Method:The epileptic animal model in rats was established by PTZ kindling， and the rats were divided into the control group， model group， carbamazepine group and Chloriti Lapis group. The brain tissue samples were detected by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry（UPLC/Q-TOF-MS）， and the experimental results were statistically analyzed by partial least squares-discriminant analysis （PLS-DA） and SPSS 18.0. Result:The metabolic fingerprints and metabolic profiles of the rat brain tissue were established， which showed that the metabolic profiles of each group had changed significantly and could be separated well among the groups. Moreover， the Chloriti Lapis group had a tendency to be closer to the control group than the carbamazepine group. Seven differential metabolites were screened， including phosphatidylserine （PS） （18∶0/18∶0）， <italic>L</italic>-glutamic acid， docosahexaenoyl ethanolamide， arachidonic acid， glucosylsphingosine， cholestane-3，7，12，24，25-pentol and lysophosphatidylcholine （LysoPC） （P-18∶0）. Except for docosahexaenoyl ethanolamide and LysoPC （P-18∶0）， Chloriti Lapis had significant intervening and regulating effects on the other five differential metabolites. There were 12 possible metabolic pathways that affected the metabolic disorder of PTZ-kindled rats， and 3 important metabolic pathways （pathway impact>0.1）， namely， <italic>D-</italic>glutamine and <italic>D-</italic>glutamate metabolism， alanine， aspartate and glutamate metabolism， and arachidonic acid metabolism， among which <italic>D-</italic>glutamine and <italic>D-</italic>glutamate metabolism was the most important metabolic pathways. Conclusion:From this point of view， Chloriti Lapis has a clear intervention effect on PTZ-kindled epileptic rats， which may be related to the intervention of the above differential metabolite contents and related metabolic pathways. It can reduce the toxic effect of excitatory neurotransmitters on neurons in brain tissue and inhibit the development of inflammation in brain tissue， so as to maintain the biological function of brain cells and slow down the occurrence of epilepsy.

Quality control analysis of brain tissue samples from Shanghai Brain Bank / 解剖学报

Objective To evaluate the feasibility of using brain tissues from Shanghai Brain Bank for the applications on biological research through the analysis of pH value of cerebrospinal fluids, RNA integrity number (RIN), transcriptome, proteome and morphology of brain tissues. Methods The pH value of fresh cerebrospinal fluid was detected by pH test paper; the RNA integrity of cryopreserved brain tissues was examined by Agilent RNA 6000 Nano chip and Agilent 2100 bioanalyzer; the transcriptome sequencing of superior temporal gyrus or caudate was performed using BGIseq-500 sequencer; the proteome of cryopreserved brain tissues was analyzed by Q Exactive HF mass spectrometer; at last, the morphology of the superior temporal gyrus was observed by HE staining. Results The pH value of the cerebrospinal fluid on average was about 6.5. The RIN values of more than 65% of brain tissues were more than 6, indicating good RNA quality. The clean reads ratio after transcriptome sequencing filtering was basically above 80%, indicating that the quality of sequencing library was high. The mass spectrometry analysis of frozen brain samples yielded more than 4000 protein groups and 30 000 peptides, indicating high quality of proteomic data. The morphology of brain tissues was relatively normal, with clearly visible neurons. Conclusion The quality of RNA and protein of brain tissues from Shanghai Brain Bank meets the basic needs for molecular and biological research, and the fixed brain samples can be used for morphological observations.

El síndrome de fatiga crónica en el curso de la hepatitis C. Presentación de un caso / Chronic fatigue syndrome in the course of Hepatitis C

RESUMEN Se supone que aproximadamente 80 millones de personas a nivel mundial están infectadas con el virus de la hepatitis C. Un aproximado del 60 % de dichos pacientes aqueja síndrome de fatiga crónica. Se presentó un paciente portador de hepatitis crónica de tipo C, con manifestaciones clínicas de síndrome de fatiga crónica por más de dos años. Se han reportado estudios internacionales que han demostrado la relación existente entre el desarrollo de la respuesta inmune y el daño que ocasiona en el tejido cerebral la infección por virus de hepatitis C. Este trabajo tiene como objetivo la presentación del primer caso que se tiene referencia (AU).

ABSTRACT It is believed that almost 80 million persons are infected with the Hepatitis C virus around the world, and 60 % of them suffer the chronic fatigue syndrome. For that reason we present the case of a patient who is a carrier of the chronic fatigue syndrome for more than two years. Reports of international research have showed the relation between the immune answer and the damage caused by the infection of the hepatitis C virus in the brain tissues. The aim of this work is presenting the first case reported in Cuba (AU).

1H-NMR Metabolomic Analysis of Brain Tissue of CUMS-Induced Depressed Mice Intervened by Iridoid Part of Valerianae Jatamansi Rhizoma et Radix / 中国实验方剂学杂志

Objective:Metabolomics was used to analyze the brain tissue samples of model mice with chronic unpredictable mild stress (CUMS) depression, in order to find out the differential metabolites related to depression and to explore the possible antidepressant mechanism of iridoid part of Valerianae Jatamansi Rhizoma et Radix (IEFV). Method:Forty-two Kunming mice were randomly divided into 6 groups, including the normal group, the model group, the fluoxetine group (2.5 mg·kg-1) and the IEFV low, medium, and high dose groups (doses were 5.73, 11.47, 22.94 mg·kg-1, respectively). The behavioral and biochemical indicators of CUMS model mice were used for pharmacodynamic evaluation with IEFV and a positive drug (fluoxetine) as the intervention drugs. Then, the effect of IEFV on endogenous substances of the brain tissue in CUMS model mice were analyzed by nuclear magnetic resonance hydrogen spectrum (1H-NMR) metabolomics, and multivariate statistical analysis was used to identify the differential metabolites and to enrich the metabolic pathways involved in the differential metabolites. Result:After modeling, the immobility time of the model mice increased significantly, their sucrose preference rate and the excitatory neurotransmitters [5-hydroxytryptamine (5-HT) and norepinephrine (NE)] decreased significantly, indicating the success of modeling. The depression was relieved after IEFV administration, mainly manifested by the recovery of the immobility time, sucrose preference rate and the excitatory neurotransmitters (5-HT and NE). Principal component analysis (PCA) of endogenous metabolites in brain tissue showed that the model group could be significantly separated from the normal group, while the IEFV groups and fluoxetine group all showed a trend of deviating from the model group to the normal group, which was consistent with the behavioral results. The results of orthogonal partial least squares discriminant analysis (OPLS-DA) showed that there were 16 different metabolites between the model group and the normal group, including 12 water-soluble metabolites and 4 liposoluble metabolites. Seven potential metabolism pathways were obtained through MetPA analysis, including metabolism of phenylalanine, metabolism of phenylalanine, tyrosine and tryptophan, metabolism of taurine and hypotaurine acid, metabolism of alanine, aspartic acid and glutamic acid, biosynthesis of valine, leucine and isoleucine, metabolism of D-glutamine and D-glutamate and tricarboxylic acid cycle (TCA). IEFV-high dose group could significantly recall 11 differential metabolites. Conclusion:IEFV may play an antidepressant role mainly by affecting energy metabolism, amino acid metabolism and neurotransmitter levels, which provides a reference for further study on the antidepressant mechanism of IEFV.