Protective effects of three kinds of borneol on different brain regions in acute cerebral ischemia/reperfusion model rats / 中国中药杂志

This study compared the ameliorating effects of L-borneol, natural borneol, and synthetic borneol on the injury of different brain regions in the rat model of acute phase of cerebral ischemia/reperfusion(I/R) for the first time, which provides a reference for guiding the rational application of borneol in the early treatment of ischemic stroke and has important academic and application values. Healthy specific pathogen-free(SPF)-grade SD male rats were randomly assigned into 13 groups: a sham-operation group, a model group, a Tween model group, a positive drug(nimodipine) group, and high-, medium-, and low-dose(0.2, 0.1, and 0.05 g·kg~(-1), respectively) groups of L-borneol, natural borneol, and synthetic borneol according to body weight. After 3 days of pre-administration, the rat model of I/R was established by suture-occluded method and confirmed by laser speckle imaging. The corresponding agents in different groups were then administered for 1 day. The body temperature was monitored regularly before pre-administration, days 1, 2, and 3 of pre-administration, 2 h after model awakening, and 1 d after model establishment. Neurological function was evaluated based on Zea-Longa score and modified neurological severity score(mNSS) 2 h and next day after awakening. The rats were anesthetized 30 min after the last administration, and blood was collected from the abdominal aorta. Enzyme-linked immunoassay assay(ELISA) was employed to determine the serum levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), IL-4, and transforming growth factor-beta1(TGF-β1). The brain tissues were stained with triphenyltetrazolium chloride(TTC) for the calculation of cerebral infarction rate, and hematoxylin-eosin(HE) staining was used for observing and semi-quantitatively evaluating the pathological damage in different brain regions. Immunohistochemistry was employed to detect the expression of ionized calcium binding adapter molecule 1(IBA1) in microglia. q-PCR was carried out to determine the mRNA levels of iNOS and arginase 1(Arg1), markers of polarization phenotype M1 and M2 in microglia. Compared with the sham-operation group, the model group and the Tween model group showed significantly elevated body temperature, Zea-Longa score, mNSS, and cerebral infarction rate, severely damaged cortex, hippocampus, and striatum, increased serum levels of IL-6 and TNF-α, and decreased serum levels of IL-4 and TGF-β1. The three borneol products had a tendency to reduce the body temperature of rats 1 day after modeling. Synthetic borneol at the doses of 0.2 and 0.05 g·kg~(-1), as well as L-borneol of 0.1 g·kg~(-1), significantly reduced Zea-Longa score and mNSS. The three borneol products at the dose of 0.2 g·kg~(-1) significantly reduced the cerebral infarction rate. L-borneol at the doses of 0.2 and 0.1 g·kg~(-1) and natural borneol at the dose of 0.1 g·kg~(-1) significantly reduced the pathological damage of the cortex. L-borneol and natural borneol at the dose of 0.1 g·kg~(-1) attenuated the pathological damage of hippocampus, and 0.2 g·kg~(-1) L-borneol attenuated the damage of striatum. The 0.2 g·kg~(-1) L-borneol and the three doses of natural borneol and synthetic borneol significantly reduced the serum level of TNF-α, and the 0.1 g·kg~(-1) synthetic borneol reduced the level of IL-6. L-borneol and synthetic borneol at the dose of 0.2 g·kg~(-1) significantly inhibited the activation of cortical microglia, and 0.2 g·kg~(-1) L-borneol up-regulated the expression of Arg1 and down-regulated the expression level of iNOS. In conclusion, the three borneol products may alleviate inflammation to ameliorate the pathological damage of brain regions of rats in the acute phase of I/R by inhibiting the activation of microglia and promoting the polarization of microglia from M1 type to M2 type. The protective effect on brain followed a trend of L-borneol > synthetic borneol > natural borneol. We suggest L-borneol the first choice for the treatment of I/R in the acute phase.

Temporal changes of Japanese encephalitits virus in different brain regions of rat.

Background & objectives: Japanese encephalitis virus (JEV) infection results in acute encephalitic illness. The affinity of JEV to different regions of brain and temporal changes in viral load have not been studied. This study was conducted to describe localization of JEV to different regions of the brain at different stages of disease in a rat model of Japanese encephalitis (JE). Methods: Twelve days old Wistar rats were inoculated intracerebrally with a dose of 3 x 106 pfu/ml of JEV. After 3, 6, 10 and 20 days post-inoculation, brains were dissected out and different regions of brain (cortex, striatum, thalamus and mid brain) were taken. Motor deficit was assessed by the rota rod and JEV RNA copies were evaluated using real-time PCR assay. Results: There was a significant increase in motor deficit in rats inoculated with JEV compared to the controls. JEV RNA copies were present in all studied regions of the brain on days 3, 6 and 10 post-inoculation. Maximum number of JEV RNA copies were present in the mid brain on days 3 and 10 post-inoculation. JEV RNA copies were not detected in any of the brain regions on day 20. Interpretation & conclusions: This study reports JEV RNA load in different brain regions of rat with higher affinity of JEV virus to thalamus and mid brain compared to other regions.

Estudos transcriptômicos no contexto da conectividade perturbada em esquizofrenia / Transcriptome studies in the context of disturbed connectivity in schizophrenia

Esquizofrenia é uma severa doença neurobiológica com fatores genéticos e ambientais desempenhando um papel na fisiopatologia. Diversas regiões cerebrais têm sido implicadas no processo da doença e estão conectadas em complexos circuitos neuronais. Nos níveis molecular e celular, a conectividade afetada entre essas regiões, envolvendo mielinização disfuncional dos axônios neuronais, bem como as alterações no nível sináptico e metabolismo energético levando a distúrbios na plasticidade sináptica, são os maiores achados em estudos post-mortem. Estudos de microarranjos investigando a expressão gênica contribuíram para os achados de alterações em vias complexas em regiões cerebrais relevantes na esquizofrenia. Além disso, estudos utilizando microdissecção e captura a laser permitiram a investigação da expressão gênica em grupos específicos de neurônios. Entretanto, deve ser mantido em mente que em estudos post-mortem, confusos efeitos de medicação, qualidade de RNAm, bem como capacidade de mecanismos regenerativos neuroplásticos do cérebro em indivíduos com história de vida de esquizofrenia, podem influenciar o complexo padrão de alterações no nível molecular. Apesar dessas limitações, estudos transcriptômicos livres de hipóteses em tecido cerebral de pacientes esquizofrênicos oferecem uma possibilidade única para aprender mais sobre os mecanismos subjacentes, levando a novas ópticas da fisiopatologia da doença

Schizophrenia is a severe neurobiological disease with genetic and environmental factors playing a role in the pathophysiology. Several brain regions have been implicated in the disease process and are connected in complex neuronal circuits. On the cellular and molecular level, affected connectivity between these regions, involving dysfunctional myelination of neuronal axons, as well as alterations on the synaptic level and energy metabolism of neurons leading to disturbances in synaptic plasticity are major findings in post-mortem studies. Microarray studies investigating genome-wide gene expression have contributed to the findings of alterations in complex pathways in relevant brain regions in schizophrenia. Moreover, first Laser-capture Microdissection studies allowed the investigation of gene expression in specific groups of neurons. However, it must be kept in mind that in post-mortem studies confounding effects of medication, mRNA quality as well as the capability of the brain for neuroplastic regenerative mechanisms in individuals with a lifetime history of schizophrenia may influence the complex pattern of alterations on the molecular level. Despite these limitations, hypothesis-free transcriptome studies in brain tissue from schizophrenia patients offer a unique possibility to learn more about underlying mechanisms, leading to new insights in the pathophysiology of the disease

Effect of Immobilization Stress on the Expression of Amyloid Precursor Protein in the Mouse Brain

BACKGROUND: The Central nervous system(CNS) plays a essential role in mediating~stress responses. However, the enact mechanism of the CNS in mediating stress responses has not been clarified sufficiently as yet. Stress may cause brain dysfunction including cognitive dysfunction which was most commonly found in Alzheimer's dementia. Amyloid precursor protein(APP) is a large, ubiquitously distributed and evolutionarily conserved molecule whose function remains unknown. Although the precise function of APP following injury to the CNS such as stab and kainic acid lesion. However, there have not been reports on the effects of stress on the expression of amyloid precursor protein in the brain. This study was undertaken to elucidate the effects of stress on the expression of APP in the mouse brain. METHODS: The several brain region was isolated from the mouse that was in the immoblization stress for 30 min, 1 hour, and 2 hours. The mouse brain was divided into 5 regions, cerebral cortex, cerebellum hippocampus, midbrain and thalamus, corpus striatum and brain stem. The change of mRNA was examined in the several brain regions using Northern blot hybridization. RESULTS: The amounts of APP mRNA in the cerebral cortex, hippocampus and brain stem were found to be significantly increased after stress for 30 minutes and to 1.each a maximum after stress for 1 hour and to normal range at stress for 2 hours. On the contray, the contents of APP mRNA in midbrain and thalamus were decreased after stress for 30 minutes and sustained after stress for 2 hours. CONCLUSION: These findings suggest that APP may not be static but functional protein reactive to stress and stress may increase the levels of APP mRNA especially in Alzheimer disease associated sites such as cerebral cortex and hippocampus, which may contriute to the pathogenesis of Alzheimer disease.