Edaravone dexborneol alleviates ischemic injury and neuroinflammation by modulating microglial and astrocyte polarization while inhibiting leukocyte infiltration.

Poststroke inflammation is essential in the mechanism of secondary injury, and it is orchestrated by resident microglia, astrocytes, and circulating immune cells. Edaravone dexborneol (EDB) is a combination of edaravone and borneol that has been identified as a clinical protectant for stroke management. In this study, we verified the anti-inflammatory effect of EDB in the mouse model of ischemia and investigated its modulatory action on inflammation-related cells. C57BL/6 male mice, which had the transient middle cerebral artery occlusion (tMCAO), were treated (i.p.) with EDB (15 mg/kg). EDB administration significantly reduced the brain infarction and improved the sensorimotor function after stroke. And EDB alleviated the neuroinflammation by restraining the polarization of microglia/macrophages and astrocyte toward proinflammatory phenotype and inhibiting the production of proinflammatory cytokines (such as IL-1ß, TNF-α, and IL-6) and chemokines (including MCP-1 and CXCL1). Furthermore, EDB ameliorated the MCAO-induced impairment of Blood-brain barrier (BBB) by suppressing the degradation of tight junction protein and attenuated the accumulation of peripheral leukocytes in the ischemic brain. Additionally, systemic EDB administration inhibited the macrophage phenotypic shift toward the M1 phenotype and the macrophage-dependent inflammatory response in the spleen and blood. Collectively, EDB protects against ischemic stroke injury by inhibiting the proinflammatory activation of microglia/macrophages and astrocytes and through reduction by invasion of circulating immune cells, which reduces central and peripheral inflammation following stroke.

Effects of congenital HCMV infection on synaptic plasticity in dentate gyrus (DG) of rat hippocampus.

This study was carried out to investigate whether the congenital HCMV infection affect the induction and maintenance of LTP /DP. Rat models of Sprague-Dawley rats congenitally infected by HCMV were made. Field excitatory postsynaptic potentials (EPSPs) were recorded in the hippocampal slices of offspring rats (50-65days) to study alterations of LTP /DP in area dentate gyrus (DG) of the hippocampus after congenital infection. The Ca(2+) and mRNA level of calmodulin (CaM) in the hippocampus neurons of the experiment group (congenital infected by HCMV) and the control group were measured;The input/output (I/O) curves of the EPSP slope PS amplitude in area DG in experiment group were significantly depressed when compared to control group (P<0.05). LTP of the EPSP slope and PS amplitude in area DG of the hippocampus was 137±4% (EPSP) and 225±11% (PS) in control rats and 115±9% (EPSP) and 163±7% (PS) in experiment rats (EPSP: F=25.29,P<0.05;PS: F=74.33 P<0.05, two-way ANOVA with Tukey test); DP of the EPSP slope and PS amplitude was 86±3% (EPSP) and 85±2% (PS) in control rats and 94±5% (EPSP) and 93±4% (PS) in congenitally infected rats (EPSP: F=5.62, P<0.05;PS: F=4.22, P<0.05, two-way ANOVA with Tukey test) . At the same time, intracellular [Ca(2+)] and mRNA level of CaM in the hippocampus neurons of the experiment group were significantly increased than that of in the controls ([Ca(2+)]: P<0.01;CaM mRNA: P<0.01) . The results demonstrate that congenital HCMV infection could reduce the range of synaptic plasticity in the Sprague-Dawley rats, which may trigger the dysfunction of learning and memory through disrupting the calcium balance.

The association of genetic polymorphisms with cerebral palsy: a meta-analysis.

AIM: The aim of our meta-analysis was to summarize quantitatively the association of genetic polymorphisms with cerebral palsy (CP). METHOD: We identified 16 studies on the association of genetic polymorphisms with CP in Pubmed, Elsevier Science Direct, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, and Wanfang. Eleven of these studies (involving a total of 2533 cases and 4432 controls) were used in the current meta-analysis. A study was included if (1) it was published up to September 2010 and (2) it was a case-control study. We excluded one study of family members because the analysis was based on linkage considerations. Meta odds ratios and 95% confidence intervals based on fixed-effects models or random-effects models were dependent on Cochran's Q statistic. We examined the relationship between alleles, as well as genotypes and susceptibility to CP. RESULTS: Meta-analysis was performed for 17 genetic polymorphisms: apolipoprotein E (ε2,ε3,ε4), methylenetetrahydrofolate reductase (MTHFR) (rs1801133), coagulation factor II (rs1799963]), coagulation factor V (rs6025), coagulation factor VII (rs5742910/rs6046), interleukin-6 (IL-6) (rs1800795), endothelial nitric oxide (rs1800779/rs1799983/rs3918226), fibrinogen ß-polypeptide (rs1800790), plasminogen activator inhibitor 1 (rs1799768/rs7242), TNF-ß lymphotoxin α precursor (rs1041981), adducin 1 (α) (rs4961), ADRB2 (rs1042714), and tumour necrosis factor α (rs1800629). We found a significant association between CP and IL-6 (rs1800795) [C vs G: odds ratio (OR) 1.79, 95% confidence interval (CI) 1.44-2.22, p<0.001; CC+GC vs GG: OR 1.72, 95% CI 1.29-2.29, p=0.002; CC vs GG+GC: OR 2.17, 95% CI 1.52-3.09, p<0.001], but no other genetic polymorphisms. INTERPRETATION: This meta-analysis demonstrated that CP is associated with the genetic polymorphism IL-6 (rs1800795).