Effects of butyphthalide on microglia polarization after intracerebral hemorrhage and the underlying mechanisms / 中南大学学报(医学版)

OBJECTIVES@#Because intracerebral hemorrhage (ICH) has high morbidity, disability and mortality, it is significant to find new and effective treatments for ICH. This study aims to explore the effect of butyphthalide (NBP) on neuroinflammation secondary to ICH and microglia polarization.@*METHODS@#A total of 48 healthy male SD rats were randomly divided into 6 groups: a sham 24 h group, a sham 72 h group, an ICH 24 h group, an ICH 72 h group, an ICH+NBP 24 h group, and an ICH+NBP 72 h group (8 rats per group). After operation, the neurological deficiencies were assessed based on improved Garcia scores and corner test. The expressions of Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), aquaporin-4 (AQP4), zonula occludens-1 (ZO-1), occludin, CD68, CD86, and CD206 were observed by Western blotting. Inflammatory cytokines were detected by ELISA. The immunofluorescence was to detect the polarization of microglia.@*RESULTS@#1) Compared with the sham groups, the expression of TLR4 (24 h: P<0.05; 72 h: P<0.01), NF-κB (both P<0.01) and Nrf2 (both P<0.01) in the perihematoma of the ICH group was increased, leading to microglia activation (P<0.01). The expressions of IL-6 (24 h: P<0.05; 72 h: P<0.01) and TNF-α (both P<0.01), the pro-inflammatory cytokines were up-regulated, and the expression of anti-inflammatory cytokine IL-4 was down-regulated (both P<0.01). Besides, the expression of AQP4 was enhanced (both P<0.01). The protein level of tightly connected proteins (including ZO-1, occludin) was decreased (all P<0.01). The neurological function of the rats in the ICH group was impaired in the 2 time points (both P<0.01). 2) Compared with the sham group at 24 h and 72 h after the intervention of NBP, the expressions of TLR4 (both P<0.05) and NF-κB (both P<0.01) were significantly declined, and the expression of Nrf2 was further enhanced (both P<0.05) in the perihematoma of the ICH+NBP group. Furthermore, the expression of M1 microglia marker was inhibited (P<0.05), and the polarization of microglia to the M2 phenotype was promoted (P<0.01). 3) In terms of inflammation after ICH, the IL-4 expression in the ICH+NBP group was increased compared with the ICH group (24 h: P<0.05; 72 h: P<0.01); the expression of IL-6 was decreased significantly in the ICH+NBP 72 h group (P<0.01); the level of AQP4 was declined significantly in the ICH+NBP 24 h group (P<0.05), there was a downward trend in the 72-hour intervention group but without significant statistical difference. 4) Compared with the ICH group, the ZO-1 protein levels were increased (24 h: P<0.05; 72 h: P<0.01), and the symptoms of nerve defect were improved eventually (both P<0.05) in the ICH+NBP groups.@*CONCLUSIONS@#After ICH, the TLR4/NF-κB pathway is activated. The M1 microglia is up-regulated along with the release of detrimental cytokines, while the anti-inflammatory cytokines are down-regulated. The expression of AQP4 is increased, the tight junction proteins from the blood-brain barrier (BBB) is damaged, and the neurological function of rats is impaired. On the contrary, NBP may regulate microglia polarization to M2 phenotype and play a role in the neuroprotective effect mediated via inhibiting TLR4/NF-κB and enhancing Nrf2 pathways, which relieves the neuroinflammation, inhibits the expression of AQP4, repairs BBB, and improves neurological functional defects.

Preventive effects of curcumin on status epilepticus induced by lithium chloride-pilocarpine / 中国医师杂志

Objective To investigate the preventive effects of curcumin for status epilepticus(SE) induced by lithium chloride-pilocarpine.Methods Totally 45 Sprague-Dawley(SD) rats were randomly divided into three groups: preventive group(n=15),non-preventive group(n=15),and control group(n=15).The latency peroid and incidence of SE were recorded.The surviving neurons were stained by using nissl staining,and the programme death cells were detected by using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) in hippocampal CA3.Results The SE incidence of preventive group was 66.7%,which was significantly lower than that of non-preventive group(P0.05).Conclusion Pretreatment of curcumin can prevent the SE induced by lithium chloride-pilocarpine and the pretreatment can not protect the neuron.

Experimental study of the relationship between the changes of GABAergic interneurons and temporal lobe epilepsy / 临床神经病学杂志

Objective To systemically discuss the role of Parvalbumin (PV), Calretinin (CR) and Calbindin-D28k (CB)-containing GABAergic interneurons in the acute onset and development of temporal lobe epilepsy.Methods Immunohistochemistry method was used to detect the changes of PV, CR and CB-containing interneuron numbers in hippocampus of temporal lobe epileptic rats induced by lithium-pilocarpine at different time points (6 h, 24 h, 7 d, 15 d, 30 d and 60 d).Results Compared with control group, no loss of PV-positive cells was observed in CA3 region at any time point in epileptic model groups, while dramatic reduction of PV-positive cells was seen in CA1 region ( P0.05). In CA1 region, the number of CB positive interneurons decreased dramatically at 6 h ( P

GM_2 gangliosidosis / 临床神经病学杂志

Objective To probe into the clinical features and pathological change of GM 2 gangliosidosis. Methods The clinical manifestations of 2 patients with late onset GM 2 gangliosidosis were reported, a biopsy of the right frontal lobe was performed for each case.Results The clinical manifestations of the late onset GM 2 gangliosidosis were nonspecific, the ballooned neurons with cytoplasmic deposits were found under the light microscopy.The deposits were membranous cytoplasmic bodies(MCB) together with zebra bodies.Conclusion The result suggested that light microscopy with electron microscopy in taking brain biopsy was very important for the diagnosis of GM 2 gangliosidosis.

Comparative study on quality of life in traditional anti-epileptic drug and topiramate treat for the patients with adults epilepsy / 临床神经病学杂志

Objective To explore the effect on quality of life in traditional anti-epileptic drug and topiramate(TPM) treat for the patients with adult epilepsy. Methods 102 patients with adults epilepsy by clinical diagnosed were randomly divided into two groups: AEDs (anti-epileptic drugs) group and TPM group. QOLIE-30 was used to evaluate 102 patients and 62 normal controls. Results QOL scores were lower in AEDs group compared with control group( P