Ginkgo Leaf Extract and Armillariella Mellea Powders Oral(银杏蜜环口服溶液) attenuates inflammation of microglia in habenular nucleus through CX3CL1-CX3CR1 axis in post stroke depression

OBJECTIVE The Ginkgo Leaf Extract and Armillariella Mellea Powders Oral(Yinxingmihuan Koufu Rongye,YXMH),a representative drug for"Treating both Brain and Heart",showed considerable clinical effects in isch⁃emic cardiovascular and cerebral vascular diseases.Recently,it is reported that YXMH has the potential for treating myocardial and cerebral ischemia related mental disorders,such as post stroke depression(PSD)and chronic heart disease(CHD)associated anxiety disorder.However,its mechanism has not been clearly elucidated.Meanwhile,increasing evidence revealed that there are close functional links between depression and habenular nucleus.The present study investigates the underlying mechanism of YXMH on attenuating the inflammation of microglia in habenular nucleus through CX3CL1-CX3CR1 axis in in a rat model of PSD.METHODS Rats were randomly devided into sham group,model group,Ginaton group(18 mg·kg^-1),Armillariella Mellea group(600 mg·kg-1),Fluoxetine group(10 mg·kg^-1),YXMH high-dose group(618 mg·kg^-1)and YXMH low-dose group(309 mg·kg^-1).The PSD model was induced by transarterial microembolization combined with sleep deprivation(2-Chloro-D-phenylalanine,PCPA,IH,200 mg·kg^-1,for 3 times,before the behavior test)in SD male rats.Then rats were treated with corresponding medicaments through gavage once a day until 3 weeks later,followed by body mass measurement,neurological deficit score evaluation,gripping strength and thermal withdrawl latency measurement,as well as depression related behavioral indicators,the open field test(OFT)and sucrose preference test.The pathological morphological changes of habenular nucleus was observed by HE staining,the expression of IBA-1 was measured and analyzed by immunohistochemistry staining,and alterations of proteins and genes related to the CX3CL1-CX3CR1 axis were analyzed using Western blotting(CX3CL1,CX3CR1)and real-time polymerase chain reaction(PCR)(CX3CL1,CX3CR1).RESULTS Compared with the sham group,rats in the model group manifested as decreased body mass,deficient neurological behavior and gripping strength,reduced loco⁃motor activity and sugar water consumption,as well as elevated thermal withdrawl latency(P<0.05,P<0.01).Mean⁃while,the pathological morphology of the habenular nucleus on the ischemic hemisphere showed significant neuronal degeneration,microglial proliferation,inflammatory cells and glia cells infiltration,together with up-regualted expression of IBA-1,CX3CL1,CX3CR1 protein and CX3CL1,CX3CR1 mRNA.YXMH attenuated inflammation of microglia in habenular nucleus through improving pathological morphology,inhibiting IBA-1 activation,down-regulating the expres⁃sion of CX3CL1 and CX3CR1 proteins and genes,and thus improved the behavior performance of ischemic injury and depression.CONCLUSION YXMH ameliorates neurological deficit and depressive behavior in rat model of PSD induced by transarterial microembolization combined with sleep deprivation,and the mechanism is probably related to attenu⁃ating inflammation of microglia in habenular nucleus through CX3CL1-CX3CR1 axis.

Research Progress in the Treatment of Poststroke Depression with Traditional Chinese Medicine

In recent years,the incidence rate of stroke has increased year by year.Post stroke depres‐sion is one of its main complications,which seriously affects the recovery of physiological functions and quality of life of stroke patients.Traditional Chinese medicine has signifi‐cant therapeutic effects in treating this disease.This article provides a classification and review of traditional Chinese medicine treatment methods for post-stroke depression,and looks forward to the current problems.

Evaluation of the curative effect of acupuncture manipulation of regulating governor vessel and unblocking brain on the patients with post stroke depression associated with anxiety

Objective： To observe the comprehensive curative effect of acupuncture manipulation of regulating governor vessel and unblocking brain for post stroke depression associated with anxiety.Methods： Sixty-four patients with post stroke depression associated with anxiety were randomly divided into 2 groups according to the random numbers generated by spss16.0 software, the group of acupuncture manipulation of regulating governor vessel and unblocking brain（group A） and medication group（group B）, with 32 patients in each group. Acupuncture manipulation of regulating governor vessel and unblocking brain was performed in group A.Bǎihuì（百会GV 20）, Shéntíng（神庭GV 24）, Yǎmén（哑门GV 15） and Dànzhōng（膻中CV 17）, Gānshū（肝俞BL 18）. Xīnshū（心俞BL 15）. Shènshū（肾俞BL 23）,Tàichōng（太冲LR 3）, Tàixī（太溪KI 3）, Shénmén（神门HT 7） and Nèiguān（内关PC 6） were selected. The treatment was conducted for once a day, and 5 times a week. Escitalopram oxalate tablets were given orally to the patients in group B for once a day. The treatment was conducted for 8 consecutive weeks in each group. The scores of Hamilton depression scale（HAMD）, Hamilton anxiety scale（HAMA）, Barthel index（BI） and Fugl-Meyer assessment（FMA） in the two groups before and after treatment were compared.Results： Comparison with the same group before treatment, HAMD score and HAMA sore in the two groups after treatment for 4 weeks and 8 weeks were all obviously lower than that in the same group before treatment（all P〈0.01）; after treatment for 8 weeks, B1 score and FMA score in the two groups were all significantly higher than that in the same group before treatment（all P〈0.01）. Comparison between two groups after treatment. HAMD score and HAMA sore in group A after treatment for 4 weeks were significantly lower than that in group B（both P〈0.05）; only the HAMA sore in group A after treatment for 8 weeks was lower than that in group B（P〈0.05）, and there was no significant difference in HAMD score in the two groups（P〉0.05）; after treatment for 8 weeks, FMA score in group A was obviously higher than that in group B（P〈0.05）, and there was no significant difference in BI score in the two groups（P〉 0.05）.Conclusion： The curative effect of acupuncture manipulation of regulating governor vessel and unblocking brain on the anxiety state and motor function of the patients with post stroke depression is superior to that of escitalopram. With regard to the improvement of depression, this acupuncture manipulation was provided with the characteristic of rapid onset, and its long-term efficacy is equivalent to that of escitalopram. In terms of the improvement of activities of daily living, the curative effect of the two methods is equally well.

Cerebral Ischemia Reperfusion Exacerbates and Pueraria Flavonoids Attenuate Depressive Responses to Stress in Mice

Previous studies have shown that mice experiencing cerebral ischemia reperfusion （CIR） and stress can serve as a model of post stroke depression （PSD）. The present study verified the acute antidepressant effects of radix puerariae extract （PE） on PSD mice through behavior and gene expression experiments. CIR was found to reduce the sucrose consumption and tyrosine hydroxylase （TH） gene expression. PE administration after CIR surgery was observed to significantly enhance the mRNA expression of TH in the hippocampus compared with the PSD group on Day 0 and Day 3 postsurgery. These findings indicate that PE contributes to the amelioration of behavior response in PSD mice, which is closely related with the protective effects of catecholamine synthesize against CIR brain damage.