miR-34b-3p Inhibition of eIF4E Causes Post-stroke Depression in Adult Mice / 神经科学通报·英文版

Post-stroke depression (PSD) is a serious and common complication of stroke, which seriously affects the rehabilitation of stroke patients. To date, the pathogenesis of PSD is unclear and effective treatments remain unavailable. Here, we established a mouse model of PSD through photothrombosis-induced focal ischemia. By using a combination of brain imaging, transcriptome sequencing, and bioinformatics analysis, we found that the hippocampus of PSD mice had a significantly lower metabolic level than other brain regions. RNA sequencing revealed a significant reduction of miR34b-3p, which was expressed in hippocampal neurons and inhibited the translation of eukaryotic translation initiation factor 4E (eIF4E). Furthermore, silencing eIF4E inactivated microglia, inhibited neuroinflammation, and abolished the depression-like behaviors in PSD mice. Together, our data demonstrated that insufficient miR34b-3p after stroke cannot inhibit eIF4E translation, which causes PSD by the activation of microglia in the hippocampus. Therefore, miR34b-3p and eIF4E may serve as potential therapeutic targets for the treatment of PSD.

The potential targets and mechanisms of modified Baihe dihuang decoction applied in post-stroke depression / 中国药房

OBJECTIVE To explore the potential targets and mechanisms of the modified Baihe dihuang decoction （MBD/ BDD） applied in post-stroke depression （PSD）. METHODS Network pharmacology was used to mine the potential targets and key pathways of MBD/BDD in the treatment of PSD. PSD model rats were induced by focal cerebral ischemia surgery combined with chronic unforeseen mild stress， and then were randomly divided into PSD model group， MBD/BDD group （12.6 g/kg， by raw drug）， and fluoxetine hydrochloride （FLX） group （positive control， 2.3 mg/kg）； a blank control group was also set up， with 8 rats in each group. Each administration group was given a corresponding medication solution by gavage once a day for 21 consecutive days. The intervention effect of MBD/BDD on depression-like symptoms in model rats was evaluated by open field and forced swimming tests. The brain tissues of rats in each group were dissected and total RNA was extracted for transcriptome sequencing and bioinformatics analysis. The mRNA and protein expressions of genes with significant changes and common neurotrophic factors were verified based on the above results. RESULTS A total of 131 MBD/BDD antidepressant-related target genes were obtained （such as IL1B and AKT1， etc.）， which were closely related to neural active ligand-receptor interactions and cyclic adenosine monophosphate signaling pathway. MBD/BDD could significantly prolong or increase the total time spent and distance traveled in the central grid of qiangzhe@cqtcm.edu.cn PSD model rats， and significantly shorten the cumulative immobility time （P＜0.05）. After treatment with MBD/BDD， the number of genes that changed in rat brain tissue was much higher than that in the FLX group， and there were significant differences in gene profiles among the PSD model group， MBD/BDD group， and FLX group. There were 1 351 differentially expressed genes （DEGs） between the MBD/BDD group and the PSD model group， of which 178 were significantly down-regulated and 1 173 were significantly up-regulated （P＜0.05）. Above 1 351 DEGs were involved in neuronal differentiation， chemical synaptic transmission regulation. They were significantly enriched in axonal guidance， cholinergic synapses and neuroactive ligand-receptor interactions. The top 30 genes in terms of up-regulation in the brain tissue of rats of MBD/BDD group were all associated with neuronal proliferation， development， differentiation， and migration. After MBD/BDD intervention， the expressions of Fezf2， Arx， Ostn， Nrgn genes， brain-derived neurotrophic factor and tyrosine kinase receptor B protein in brain tissue of rats were significantly increased （P＜0.05）. CONCLUSIONS The anti-PSD effect of MBD/BDD may be related to the up-regulation of the expression of genes related to neuronal proliferation， development， differentiation and migration， as well as the promotion of neural structural and functional repair.

Effects of electroacupuncture at "Siguan" points on the expression of colonic 5-hydroxytryptamine and fecal short-chain fatty acids in rats with post-stroke depression / 中国针灸

OBJECTIVE@#To observe the effects of electroacupuncture at "Siguan" points on behavior, colonic 5-hydroxytryptamine (5-HT) and fecal short-chain fatty acids (SCFAs) in rats with post-stroke depression (PSD), and explore the effect mechanism of electroacupuncture at Siguan points on PSD.@*METHODS@#Fifty SD rats were randomly divided into a sham-operation group, a stroke group, a PSD group, a drug group and an electroacupuncture group, with 10 rats in each one. The stroke model was established by middle cerebral artery occlusion (MCAO) method in the stroke group; except for the sham-operation group, the rats in the other groups were intervened with MCAO combined with solitary and chronic unpredictable mild stress (CUMS) to establish PSD model. In the electroacupuncture group, electroacupuncture was delivered at "Hegu" (LI 4) and "Taichong" (LR 3), with disperse-dense wave, 2 Hz/10 Hz in frequency, for 30 min in each intervention, once daily, for consecutive 21 days. Simultaneously, distilled water (0.01 L•kg-1•d-1) was administrated intragastrically. Fluoxetine solution (2.33 mg•kg-1•d-1) was given by gavage , once a day and for 21 days in the drug group. The same procedure of fixation and gavage with distilled water were adopted in the sham-operation group, the stroke group and the PSD group. Separately, before stroke modeling, after PSD modeling and after 21-day intervention, the consumption of sugar water and the scores of horizontal movement and vertical movement in open-field test were observed. After 21-day intervention, the content of colonic 5-HT was detected by immunohistochemical method, and that of fecal SCFAs was determined by gas chromatography mass spectrometry.@*RESULTS@#After PSD modeling, compared with the stroke group, the sugar water consumption, the horizontal movement scores and vertical movement scores of the open-field test were all reduced in the PSD group, the drug group and the electroacupuncture group (P<0.05). After 21-day intervention, the sugar water consumption and the scores of horizontal movement and vertical movement of the open-field test were increased in the drug group and the electroacupuncture group (P<0.05) when compared with the PSD group; and the horizontal movement score in the electroacupuncture group was lower than that of the drug group (P<0.05). Compared with the sham-operation group, the contents of total fecal SCFAs and acetic acid were lower in the stroke group (P<0.05), and the contents of colonic 5-HT and total fecal SCFAs, acetic acid, propionic acid and butyric acid were reduced in the PSD group (P<0.05). In comparison with the PSD group, the contents of colonic 5-HT and total fecal SCFAs, acetic acid and propionic acid were increased in the drug group and the electroacupuncture group (P<0.05); and the content of colonic 5-HT in the electroacupuncture group was lower than that of the drug group (P<0.05). The level of colonic 5-HT was positively correlated with the contents of total fecal SCFAs and propionic acid (r=0.424, P=0.005; r=0.427, P=0.004).@*CONCLUSION@#Electroacupuncture at "Siguan" points can relieve the depression-like behavior of PSD rats, and its underlying mechanism may be related to the regulation of fecal SCFAs, which affects the release of colonic 5-HT.

Predictive value of Post-stroke Depression Prediction Scale combined with the Early Symptom Measurement of Post-Stroke Depression-Short Form for post-stroke depression / 中国实用护理杂志

Objective:To analyze the efficacy of the Post-stroke Depression Prediction Scale (DePreS) combined with the Early Symptom Measurement of Post-Stroke Depression-Short Form (ESMPSD-SF) in predicting post stroke depression (PSD).Methods:This study was a cross-sectional survey, using convenience sampling method to select 185 stroke patients admitted to Henan Provincial People′s Hospital from June 2019 to May 2021 as the research subjects. The DePreS, ESMPSD-SF, and general information questionnaire were used to investigate them.Results:The incidence of PSD was 36.76% (68/185). The DePreS and ESMPSD-SF scores in the PSD patients were (6.29 ± 8.77), (33.83 ± 6.78) points, respectively, significantly higher than those in the non-PSD patients (-2.05 ± 5.70), (26.51 ± 5.56) points, with statistically significant differences ( t=7.06, 7.97, both P<0.05). Logistic regression analysis showed that DePreS and ESMPSD-SF scores, marital status, and the number of comorbidities were predictive factors for PSD occurrence ( P<0.05). The AUC of DePreS for diagnosing PSD was 0.777, with an optimal diagnostic point of 2 points, a sensitivity of 59.42%, and a specificity of 80.71%; the AUC of the ESMPSD-SF for diagnosing PSD was 0.792, with an optimal diagnostic point of 28 points, a sensitivity of 78.26%, and a specificity of 74.14%. The sensitivity, specificity, and AUC of DePreS combined with ESMPSD-SF in the diagnosis of PSD were 82.61%, 83.62%, and 0.886, respectively. The differences were statistically significant compared to the AUC evaluated separately by DePreS or ESMPSD-SF ( Z=3.21, 3.49, both P<0.05). Conclusions:The combination of DePreS and ESMPSD-SF had a higher detection efficiency for PSD, and the combination of the two is more suitable for assessing PSD risk in stroke patients.

Research progress in treatment of post-stroke depression with Bushen Shugan method / 国际中医中药杂志

Traditional Chinese Medicine (TCM) has its own unique features in the treatment of post-stroke depression (PSD). The kidney is the congenital foundation and is closely related to the brain. Kidney deficiency runs through the entire course of stroke. Liver regulates the normal operation of qi in the human body, which is closely related to depression syndrome. Kidney deficiency and liver depression affect each other. The treatment of PSD with the Bushen Shugan (tonifying the kidney and soothing the liver) method has achieved good efficacy in clinic. The method of tonifying kidney and soothing liver can not only reflect the holistic view of TCM and the association of viscera, but also coordinate the relationship between body and spirit. In the future, the development direction of PSD in TCM research should be to further strengthen the concept of co-regulation of body and spirit and integration of brain and viscera.

Effects of different acupuncture schemes on neurotransmitters and related inflammatory factors in rats with post-stroke depression / 中国康复理论与实践

ObjectiveTo investigate the effects of different acupuncture schemes on behaviors, neurotransmitters and inflammation-related factors in post-stroke depressed (PSD) rats. MethodsA total of 72 healthy male Sprague-Dawley rats were randomly divided into normal group, model group, drug control group, scalp acupuncture group, abdominal acupuncture group and combined acupuncture group, 12 rats in each group. The PSD model was prepared using a combination of middle cerebral artery occlusion and chronic unpredictable mild stimulation (CUMS) for the model and each intervention groups. The drug control group was administered fluoxetine, the scalp acupuncture group accepted acupuncture at Baihui (DU 20) and Yintang (EX-HN3), while the abdominal acupuncture group at Zhongwan (RN 12) and Guanyuan (RN 4), the combined acupuncture group at all the four acupoints, for 21 days. They were assessed with Longa neurological function score, body mass, open-field test and sugar-water preference test on the 0 (before modeling), the seventh (before CUMS), the 14th (before treatment) and the 35th day (after treatment). The levels of 5-hydroxytryptamine (5-HT), dopamine (DA), norepinephrine (NE), interferon-γ (INF-γ), tumor necrosis factor⁃α (TNF⁃α) and macrophage migration inhibitory factor (MIF) in the serum were determined with ELISA on the 35th day. Results The neurological function score was lower in the drug control group and the combined acupuncture group thanin the model group (P < 0.01) on the 35th day; while the body mass was higher in the drug control group, the abdominal acupuncture group and the combined acupuncture group than in the model group (P < 0.01); and the number of horizontal span frames, the number of uprightness and the sugar water consumption were higher in the drug control group, the scalp acupuncture group, the abdominal acupuncture group and the combined acupuncture group than in the model group (P < 0.05). There was no significant difference among the four intervention groups (P > 0.05). The levels of 5-HT, DA and NE were higher in the four intervention groups than in the model group (P < 0.01), and the levels of IFN-γ, TNF⁃α and MIF were lower (P < 0.01). 5-HT level was higher in the combined acupuncture group than in the scalp acupuncture group and the abdominal acupuncture group, and the levels of IFN-γ, TNF⁃α and MIF were lower (P < 0.01); the levels of DA and NE was higher in the combined acupuncture group than in the abdominal acupuncture group (P < 0.01). ConclusionThe combination of scalp acupuncture and abdominal acupuncture can improve behavior, neurotransmitters and inflammatory factors of PSD rats, like fluoxetine. Scalp or abdominal acupuncture alone is still effecive, and can be used secondarily.

Tiaoshen Jieyu acupuncture combined with sertraline hydrochloride tablet for post-stoke depression: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the clinical efficacy between Tiaoshen Jieyu acupuncture (acupuncture for regulating mind and relieving depression) combined with sertraline hydrochloride tablet and simple sertraline hydrochloride tablet for post-stroke depression (PSD).@*METHODS@#A total of 76 patients with PSD were randomized into an observation group (38 cases, 6 cases dropped off) and a control group (38 cases, 4 cases dropped off). Both groups were treated with conventional treatment i.e. controlling blood pressure and anti-inflammation. Sertraline hydrochloride tablet was given orally in the control group, 20 mg a time, once a day. On the basis of the treatment in the control group, Tiaoshen Jieyu acupuncture was applied at Baihui (GV 20), Yintang (GV 24+), Neiguan (PC 6), Taichong (LR 3), etc. in the observation group, Baihui (GV 20) and Yintang (GV 24+) were connected to electroacupuncture, with disperse-dense wave, 2 Hz/100 Hz in frequency, 30 min a time, once a day, 6 times a week. Treatment of 8 weeks was required in both groups. Before and after treatment, the scores of Hamilton depression scale (HAMD), National Institutes of Health stroke scale (NIHSS), Barthel index (BI) and Pittsburgh sleep quality index (PSQI) were observed respectively, the therapeutic efficacy and rate of adverse reactions were evaluated in the two groups.@*RESULTS@#After treatment, the scores of HAMD, NIHSS and PSQI were lower while BI scores were higher than those before treatment in both groups (P<0.05); the scores of HAMD, NIHSS and PSQI in the observation group were lower while BI score was higher than those in the control group (P<0.05). The total effective rate was 93.8% (30/32) in the observation group, which was higher than 70.6% (24/34) in the control group (P<0.05). The rate of adverse reactions was 9.4% (3/32) in the observation group, which was lower than 32.4% (11/34) in the control group (P<0.05).@*CONCLUSION@#Tiaoshen Jieyu acupuncture combined with sertraline hydrochloride tablet can improve the depression degree, neurological function, activity of daily living and sleep quality in patients with post-stroke depression, the clinical efficacy is superior to simple sertraline hydrochloride, and can alleviate the adverse reactions caused by medication.

Factors Influencing Depression In Patients Of Cerebrovascular Accidents-A Study

Background: Post Stroke Depression (PSD) is one of the most frequent Neuropsychiatric consequences of stroke. It affects almost 29%-70% of Stroke Survivors (SS). There is paucity of research data in determining the risk factors and especially severity and associa?on of depression with site of lesion loca?on in Indian community. Aim and Objec?ves: To determine factors associated with PSD and associa?on between Socio-demographic profiles, Stroke symptoms, Site of lesion with depression. Materials and Methods: It’s a cross-sec?onal study including par?cipants from the outpa?ents sec?on of Department of Neurology at Prathima Ins?tute of Medical Sciences. A predetermined sample size of 60 pa?ents with CVA pa?ents was enrolled in the study and their socio demographic details are collected along with administering Beck’s Depression Inventory for Depression. Neuro-imaging provided informa?on on lesion loca?on. Collected data was analysed using SPSS version 19 and using descrip?ve and inferen?al sta?s?cs. Results: In this study 18 out of 60 subjects with stroke were diagnosed with PSD. Risk factors found to be mainly associated with PSD are lack of family support, Joint family types, Stroke with Aphasia, Cranial Nerve involvement and Motor System weakness whereas, Substance use is found to be a protec?ve factor. Significant numbers of subjects were found to have le?-anterior-sub-cor?cal lesions associated with PSD. Conclusion: This study highlights the variables which are to be considered in the recogni?on of PSD for Neurologists and Mental health care workers for early interven?on and a be?er outcome in view of stroke recovery

A cross-sectional study on clinical correlates of post-stroke depression in a tertiary health-care system of India

Objectives: The aim of our study is to determine the relation of the type of stroke and site of lesion and medical comorbidities such as diabetes and hypertension with the severity of depression, HAM-D scores as well as age and gender of these patients. Materials and Methods: The present study was a hospital-based cross-sectional study conducted over 2 months that included 61 patients from neurology OPD of IMS and SUM Hospital, Bhubaneswar. Purposive sampling was done. The patients fulfilling the inclusion and exclusion criteria were first assessed using a semi-structured questionnaire to obtain the sociodemographic data. Clinical psychiatric evaluation and detailed mental state examination were done. Based on the clinical findings and using ICD 10-DCR criteria, the 61 patients with CVA were segregated as depressive and non-depressive categories. HAM-A and HAM-D scales were applied on both the groups. MRI findings done at the time of the attack were obtained. Further research is needed to identify the mechanisms of depression and why antidepressants lead to improved physical and cognitive recovery and decreased mortality. Results: Age of onset, gender, type of stroke and hemispherical involvement do not show any correlation with PSD. However, we found that the HAM-D scores were much higher in PSD patients with lacunar lesions as compared to non-depressive post stroke patients. Conclusion: Lacunar lesions may be involved in the psychopathology of depressive illness among stroke survivors. This could help us predict the occurrence of depressive illness among stroke patients with lacunar lesions. HAM-D and HAM-A may be used to detect anxiety and depressive symptoms among these patients.

Effects of post-stroke depression on sleep quality and cognitive dysfunction / 公共卫生与预防医学

Objective To analyze the effects of post-stroke depression on sleep quality and cognitive dysfunction, and to provide evidence for the intervention of post-stroke depression. Methods A retrospective analysis was performed on 712 patients with stroke in Shiyan region from October 2018 to October 2020. According to the occurrence of post-stroke depression, they were divided into experimental group (post-stroke depression, n=294) and control group (non-post-stroke depression, n=418). The experimental group was divided into mild group (n=89), moderate group (n=128) and severe group (n=77) according to the HAMD score. PSQI score and MOCA score were compared between the two groups. The Pearson correlation analysis of HAMD score with sleep quality and cognitive dysfunction was analyzed. Results THE PSQI score of the experimental group was significantly higher (t =40.961, P<0.05). The MOCA score of the experimental group was significantly lower (t =27.525, P<0.05). PSQI score in mild group was significantly lower than that in moderate and severe groups (t1 =19.988, t2 =22.634, P<0.05). The PSQI score of moderate group was significantly lower (t3 =7.157, P<0.05). MOCA evaluation in mild group was significantly higher than that in moderate and severe groups (t1 =8.180, t2 =14.568, P<0.05). The MOCA rating of moderate group was significantly higher than that of severe group (t3 =7.947, P<0.05). Pearson correlation analysis showed that post-stroke depression was significantly positively correlated with PSQI score (r=0.713 , P<0.05). Poststroke depression was negatively correlated with MOCA score (r = -0.691, P<0.05). Conclusion The patients with poststroke depression are often accompanied by sleep disorder and cognitive dysfunction. The higher the HAMD score, the more serious the sleep disorder and cognitive dysfunction.

Transcranial magnetic stimulation improves the effectiveness of psychological intervention in relieving post-stroke depression / 中华物理医学与康复杂志

Objective:To investigate any effect of supplementing psychological intervention with repeated transcranial magnetic stimulation (rTMS) in treating depression, improving neurological functioning and improving the life quality of depressed stroke survivors.Methods:A total of 228 patients with post-stroke depression (PSD) were randomly divided into a psychological intervention group, an rTMS treatment group and a combined treatment group, each of 76. In addition to routine stroke treatment and anti-depressant drug treatment, the psychological intervention group received psychological counseling and the rTMS group was given rTMS at 10Hz for 8 weeks. The combined group received both. Before and after the intervention, depression was quantified using the 24-item Hamilton Depression Scale. The National Institutes of Health Stroke Scale was used to quantify neurological functioning. And cognitive functioning was assessed with the Cognitive Function Assessment Scale. Life quality was assessed using the Stroke-specific Quality of Life Scale.Results:After the 8 weeks, significant improvement was observed in the average scores of all three groups on all of the measurements. The combined group had improved significantly more than the other two groups in terms of all of the dimensions studied. The combined group′s clinical remission rate (38.16%) and response rate (85.53%) were significantly higher than those of the other two groups.Conclusions:Repetitive transcranial stimulation can significantly improve the effectiveness of psychological counseling in treating PSD after a stroke. Using them jointly is worthy of application in the clinical practice.

Effects of foraging exercise on behavior and the expression of 5-hydroxytryptamine 1A and transforming growth factor β1 in the frontal lobes of rats modelling post-stroke depression / 中华物理医学与康复杂志

Objective:To explore the effect of foraging exercise (FE) on the behavior of rats with post-stroke depression (PSD) and the expression of 5-Hydroxytryptamine 1A (5-HT1A) receptor and transforming growth factor β1 (TGF-β1) in their frontal lobes.Methods:Thirty-six healthy male Sprague-Dawley rats were randomly divided into an ischemia-reperfusion (I/R) group, a PSD group and a PSD+ FE (FE) group, each of 12. The right middle cerebral artery of each was occluded using the thread occlusion method with 1.5h of ischemia. In the PSD and FE groups, mild stimulation was administered at unpredictable intervals over 3 weeks beginning 1 week after the successful modeling. The rats in the I/R group were raised in a group. Those in the PSD group were raised in individual cages. Those in the FE group were raised in a single cage and foraged freely for a total of 4 weeks. Four and eight weeks after the modeling, the body weights were measured, and the open field, social interaction (SIT) and sugar preference tests were administered to all of the groups. Four weeks later, all of the rats were sacrificed and their brains were sliced and stained. The expression of 5-HT1A receptor and TGF-β1 in the frontal lobe was detected using western blotting.Results:One week after modeling, there was no significant difference in average body weight or the average behavioral scores among the three groups. After four weeks the PSD and FE groups had significantly lower average body weight than the I/R group, fewer counts of rearing and grid crossing, longer SIT latency, less interaction time and lower average sugar preference (all significant differences). After eight weeks the average body weight had increased in each group. SIT latency had shortened and interaction time had increased in the FE group, and the rearing and grid crossing counts and sugar preference had increased in the PSD and FE groups. At that point the FE group had significantly greater average body weight than the PSD group, more counts of rearing and grid crossing, shorter SIT latency, increased interaction time, and greater sugar preference. The ratio of residual brain volume in the right hemisphere of the PSD and FE groups was significantly lower on average than in the I/R group. However, there was no significant difference in the right residual brain volume ratio between the PSD and FE groups. Staining revealed that the pathological changes in the frontal lobes of the FE group had been significantly relieved compared with the PSD group. Eight weeks after the operation the increases in average 5-HT 1A receptor and TGF-β1 levels in the FE group were significantly greater than in the PSD group.Conclusion:Foraging can relieve the depressive symptoms of rats modeling post-stoke depression. The mechanism may be related to alleviating the pathological damage and increasing the expression of 5-HT1AR and TGF-β1 in the frontal lobe. Early chronic stress may increase the volume of cerebral infarction, at least in rats.

Effect of edaravone dexborneol on anxious-and depressive-like behaviors and its mechanism in rats with cerebral ischemia-reperfusion / 中华行为医学与脑科学杂志

Objective:To observe the effect of edaravone dexborneol on anxiety and depression after stroke in rats, and to explore its possible mechanism.Methods:Totally 120 healthy adult male SD rats were randomly divided into sham operation group (sham), ischemia-reperfusion group (MCAO), edaravone group (Eda) and edaravone dexborneol group (ED) with 30 in each group.The middle cerebral artery occlusion (MCAO) model was established by thread occlusion.Rats in ED group and Eda group were intraperitoneally injected with edaravone(8 mg·kg -1·d -1) and edaravone dexborneol(edaravone: 8 mg·kg -1·d -1, dexborneol: 2 mg·kg -1·d -1) respectively.And rats in the other two groups were intraperitoneally injected with the same volume of normal saline.Some rats were killed after continuous administration for 3 days to detect molecular indexes, and the remaining rats were tested for behavior after continuous administration for 14 days.The levels of neclear factor κB(NF-κB)、phosphorylated NF-κB(p-NF-κB)、tumor necrosis α(TNF-α)、interleukin 1β(IL-1β) were detected by Western blot.The mRNA levels of TNF-α, IL-1β, cluster of differentiation 86(CD86), cluster of differentiation 206(CD206), inducible nitric oxide synthase(iNOS) were detected by RT-qPCR.M1 type microglia labeled with CD68, microglia labeled with ionized calcium binding adaptor molecule 1(Iba1) and neurons labeled with microtubule-associated protein 2(MAP2) were detected by immunofluorescence staining.The cerebral infarction volume was measured by TTC staining.Depression and anxiety behavior after stroke in rats was observed by the open field test and elevated plus maze test.SPSS 17.0 software was used for statistical analysis of the data.One-way ANOVA was used for multiple group comparison, and LSD-t test was used for pairwise comparison. Results:(1) The behavioral results showed that 14 days after ischemia-reperfusion, the number of entering into the open arm, the time spent in the open arm, and the time spent in the central area of the open field in the MCAO group were lower than those in the sham group ( t=20.77, 6.02, 14.63, all P<0.05). The number of entering into the open arm, the time spent in the open arm, and the time spent in the central area of the field in the ED group ( (16.22±0.49) times, (69.11±17.08) s, (3.80±0.37) s) were higher than those in the MCAO group ( (8.14±0.60) times, (41.18±9.81) s, (0.33±0.39) s) ( t=4.69, 0.38, 2.27, all P<0.05) and Eda group ( (11.11±0.26) times, (45.26±17.16) s, (1.14±0.19) s) ( t=8.63, 2.50, 7.86, all P<0.05). (2) Western blot results showed that 3 days after ischemia-reperfusion, p-NF-κB/NF-κB, TNF-α, and IL-1β levels in the MCAO group were higher than those in the sham group ( t=15.35, 12.35, 7.23, all P<0.05). The levels of p-NF-κB/NF-κB (0.49±0.02), TNF-α (0.73±0.03), IL-1β (0.61±0.01) of ischemic penumbra cortex in ED group were significantly lower than those of the MCAO group ( (1.14±0.05), (1.13±0.07), (1.34±0.14)) ( t=14.58, 7.86, 5.65, all P<0.05) and Eda group ( (0.93±0.03), (0.89±0.02), (1.04±0.36) ) ( t=9.82, 3.07, 3.30, all P<0.05). (3) RT-qPCR results showed that the level of TNF-α mRNA (1.98±0.18), IL-1β mRNA (2.00±0.35), CD86 mRNA (1.56±0.20) and iNOS mRNA (2.01±0.12) in the peri-infarct cortex of ED group were lower than those in the MCAO group ( (5.12±0.24), ( 8.15±0.22), (6.03±0.13), (7.20±0.09) ) ( t=7.86, 16.88, 16.55, 37.25, all P<0.05) and Eda group ( (2.85±0.07), (5.43±0.26), (2.67±0.27), (3.58±0.11) ) ( t=3.71, 9.41, 4.13, 11.30, all P<0.05). The level of CD206 mRNA in the peri-infarct cortex of the ED group (3.98±0.25) was higher than that in the MCAO group (2.00±0.11) ( t=7.08, P<0.05) and Eda group (3.17±0.09) ( t=3.25, P<0.05). (4) The results of immunofluorescence staining showed that the ratio of polarized M1 microglia in the peri-infarct cortex and striatum in the ED group ((20.36±9.23)%, (18.26±5.98)%)were lower than those in the MCAO group ( (83.69±12.79)%, (61.25±33.26)%) ( t=5.23, 3.02, both P<0.05) and Eda group((42.16±13.13)%, (40.23±14.22)%)( t=3.12, 2.08, both P<0.05). In addition, the number of neurons marked with MAP2 of peri-infarct cortex in the MCAO group was lower than that in the sham group( t=8.02, P<0.05), and the number of neurons marded with MAP2 of peri-infarct cortex in the ED group ((53.07±17.90) /scope) was higher than that in the MCAO group ( (26.27±9.95) /scope) ( t=6.89, P<0.05) and Eda group ( (38.69±12.03)/scope) ( t=5.26, P<0.05). (5) The results of TTC staining showed that the cerebral infarction volume in ED group ( (10.31±1.03)%) was lower than that in the MCAO group ( (34.71±1.74)%) ( t=15.31, P<0.05) and Eda group ( (26.05±1.00)%) ( t=9.88, P<0.05). Conclusion:Edaravone dexborneol can alleviate anxiety and depression in rats with cerebral ischemia-reperfusion, which may be related to the inhibition of M1 microglial polarization, the down-regulation of NF-κB signaling pathway and the enhancement of neuronal structural stability.

Effects of foraging exercise on depressive-like behaviors and expression of transforming growth factor-β1 in hippocampus of rats with ischemic stroke after chronic stress / 中华行为医学与脑科学杂志

Objective:To explore the effects of foraging exercise (FE) on depressive-like behaviors and expression of transforming growth factor-β1 (TGF-β1) in hippocampus of rats with ischemic stroke after chronic stress.Methods:The right middle cerebral artery occlusion (MCAO) model was used in 30 male adult clean grade SD rats by suture method.According to the body weight, rats were evenly divided into stroke group ( n=10) and chronic unpredictable mild stimulation (CUMS) group ( n=20). Rats of CUMS group received stress induction 1 week after operation and lasted for 3 weeks. Then, according to random number generator of SPSS 24.0 software, the depression rats were divided into post-stroke depression (PSD) group( n=10) and FE groups ( n=10). The FE group received free FE intervention for 4 weeks. Body weight, water maze test, novelty inhibition feeding test (NSFT) and sucrose preference test (SPT) were performed at the end of the 1st, 4th and 8th week, respectively. The expression of TGF-β1 in hippocampus was detected by Immunohistochemistry (IHC) and Western blot (WB), and the levels of TGF-β1 and TNF-α in serum were detected by ELISA. SPSS 24.0 software was used for statistical analysis. The behavioral data were compared by two factor repeated measurement analysis of variance. One way ANOVA was used for comparison among groups, and LSD test was used for further pairwise comparison. Results:(1) The interaction between group and time had statistical significance on body weight, latency and food intake of NSFT and sucrose preference index(SPI) ( F=2.936-12.098, all P<0.05). After 4 weeks, compared with the stroke group((343.80±19.34)g, (12.10±6.97)s, (0.75±0.09)%), the body weight((307.80±17.23)g, (305.30±24.39)g), and SPI((0.52±0.06)%, (0.53±0.07)%) of PSD group and FE group were lower and the NSFT latency((21.70±7.02)s, (22.40±0.84)s) was longer (all P<0.05). After 8 weeks, SPI in FE group was higher than that in PSD group ( P=0.045). There were significant differences in body weight of three groups, NSFT latency and SPI of PSD group and FE group, and food intake of stroke and FE group ( F=8.478-196.548, all P<0.05). There was no interaction between group and time in the water maze test. Main effect of time ( P=0.034) and main effect of group ( P<0.01) had statistical significance on escape latency. The escape latency after 4 weeks was longer than that after 1 week ( P=0.003). The latency of PSD group was longer than that of stroke group ( P=0.005), and latency of FE group was shorter than that of the PSD group ( P<0.01). The main effect of group had statistical significance in the number of crossing quadrant ( P<0.01). The number of crossing quadrant of FE group was less than that of PSD group ( P<0.01). (2) Immunohistoche mistry staining showed that compared with the stroke group, the expression of TGF-β1 was down-regulated in 3 areas of hippocampus of PSD group (CA1, CA3 and DG) ( t=5.449-9.353, all P<0.01). Compared with stroke group, the expression of TGF-β1 of CA1 ( t=7.433, P<0.01) in FE group was down-regulated, but was up-regulated in CA3 ( t=3.342, P<0.05) of FE group. Compared with the PSD group, the expression of TGF-β1 was up-regulated in CA3 and DG of FE group ( t=7.811, 8.790, both P<0.01). (3) Western blot results: Compared with stroke group, the expression of TGF-β1 in hippocampus of PSD group was down-regulated ( t=3.255, P<0.01). Compared with the PSD group, the expression of TGF-β1 in hippocampus of FE group was up-regulated ( t=2.906, P<0.05). (4) ELISA detection showed that compared with the stroke group, the levels of TGF-β1 decreased ( t=2.224, P<0.05), but TNF-α increased ( t=6.127, P<0.01) in PSD group.Compared with the PSD group, the expression of TGF-β1 in FE group increased significantly ( t=4.417, P<0.01). Conclusion:Foraging exercise can improve the depressive behavior symptoms of ischemic stroke rats after chronic stress, and its mechanism may be related to the increasing expression of TGF-β1, which can alleviate the inflammatory reaction in hippocampus.

Research progress on non-pharmacological therapies for post-stroke depression / 四川精神卫生

This article aims to review the clinical efficacy of existing non-pharmacological therapies for post-stroke depression （PSD）， in order to provide references for the comprehensive treatment of PSD. As a common complication of stroke， PSD seriously affects patients' rehabilitation and daily life， and brings a heavy burden to patients and their families. Non-pharmacological therapy is an important intervention approach for PSD. Therefore， this article gives a review on the non-pharmacological therapies for PSD including psychotherapy and physical therapy.

Effect of Shunao Jieyu Decoction on Intestinal Flora in Patients with Post-stroke Depression / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Shunao Jieyu decoction on intestinal flora in patients with post-stroke depression. MethodSixty patients with post-stroke depression of Qi stagnation， blood stasis， and phlegm obstruction were selected and divided into a treatment group （30 cases， Shunao Jieyu decoction） and a control group （n=30， paroxetine hydrochloride tablets） according to the random number table. All patients were treated correspondingly for eight weeks. The scores of traditional Chinese medicine（TCM） syndrome， Hamilton rating scale for depression（HAMD）， National Institutes of Health stroke scale（NIHSS）， and activities of daily living（ADL）before and after treatment were compared between the two groups. High-throughput sequencing was used to analyze the diversity of fecal flora and the distribution of taxonomical levels in two groups before and after treatment. ResultThe post-treatment TCM syndrome score， HAMD score， and NIHSS score were lower than those before treatment in the same group （P<0.05）， while the post-treatment ADL score was higher than that before treatment （P<0.05）. Compared with the control group after treatment， the treatment group showed decreased TCM syndrome score （P<0.05）. No significant difference was observed in the HAMD score， NIHSS score and ADL score between the two groups after treatment. The total effective rate of the treatment group was 90% （27/30）， which was superior to 66.3% （19/30） of the control group （χ2=5.863， P<0.05）. After treatment， the average values of Chao1 index， Observed species index， Shannon index， Simpson index， and Pielou's evenness index of intestinal flora diversity in the treatment group increased without significant difference， while the average value of the Good's Coverage index remained unchanged in the same group. At the phylum level， the abundance of Bacteroidetes increased. At the family level， the abundance of Bacteroidaceae increased. At the genus level， the abundance of Bacteroidetes increased. ConclusionShunao Jieyu decoction can effectively improve the clinical TCM symptoms of patients with post-stroke depression， relieve neurological impairment， improve the ability of daily living， and change the diversity and abundance of the intestinal flora of patients at different taxonomic levels.

Pharmacological Mechanism of Curcumae Radix in Treatment of Post-stroke Depression： A Review / 中国实验方剂学杂志

Post-stroke depression， a common mental complication after stroke， seriously affects the quality of life and even endangers the life safety of patients. It is difficult to be cured due to the complex and diverse pathogenesis. At present， the widely accepted pathogenesis mechanisms include inflammatory mechanism， neurotransmitter mechanism， and endocrine mechanism. According to the theory of Chinese medicine， Qi stagnation， blood stasis， and phlegm turbidity lead to the occurrence of mental diseases after stroke. Curcumae Radix， as a commonly used Chinese herbal medicine， can activate blood circulation for relieving pain， regulate Qi， and relieve depression. The summary of the medication rules of DENG Tie-tao， ZHANG Xue-wen and other Chinese medical physicians showcases that Curcumae Radix is frequently used in the clinical treatment of depression， stroke， and post-stroke depression. Modern pharmacological studies have demonstrated that Curcumae Radix contains β-sitosterol， curdione， curcumin and other medicinal ingredients. This study reviewed the pharmacological effects of effective components in Curcumae Radix and the pharmacological mechanism in the treatment of post-stroke depression and summarized the processing methods of Curcumae Radix， aiming to clarify the important role and determine the optimal processing method of Curcumae Radix in the treatment of post-stroke depression. The results indicate that Curcumae Radix has the effects of regulating neurotransmitters， inhibiting neuroinflammation， protecting neurons， regulating neuroendocrine and antithrombosis， which can prevent and treat post-stroke depression through multiple components， targets， and pathways. The wine-processed Curcuma longa has the best effect.

The etiologies of post-stroke depression: Different between lacunar stroke and non-lacunar stroke

Abstract Objectives: Depression is common after both lacunar stroke and non-lacunar stroke and might be associated with lesion locations as proven by some studies. This study aimed to identify whether lesion location was critical for depression after both lacunar and non-lacunar strokes. Methods: A cohort of ischemic stroke patients was assigned to either a lacunar stroke group or a non-lacunar stroke group after a brain MRI scan. Neurological deficits and treatment response was evaluated during hospitalization. The occurrence of depression was evaluated 3 months later. Logistic regressions were used to identify the independent risk factors for depression after lacunar and non-lacunar stroke respectively. Results: 83 of 246 patients with lacunar stroke and 71 of 185 patients with non-lacunar stroke developed depression. Infarctions in the frontal cortex, severe neurological deficits, and a high degree of handicap were identified as the independent risk factors for depression after non-lacunar stroke, while lesion location was not associated with depression after lacunar stroke. Conclusion: The main determinants for depression after lacunar and non-lacunar stroke were different. Lesion location was critical only for depression after non-lacunar stroke.

Effect of Music Therapy Based on Scalp Acupuncture on Post-stroke Depression: Study with Resting-state Functional Magnetic Resonance Imaging / 中国康复理论与实践

Objective:To observe the effects of music therapy combined with scalp acupuncture on post-stroke depression (PSD) using resting-state functional magnetic resonance imaging (rs-fMRI). Methods:From December, 2018 to November, 2019, 40 patients with PSD from Rehabilitation Department of the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine were randomly divided into control group (n = 20) and observation group (n = 20). Both groups received routine rehabilitation and scalp acupuncture, while the observation group received music therapy as acupuncture, for four weeks. They were assessed with Hamilton Depression Scale (HAMD-17), Pittsburgh Sleep Quality Index (PSQI) and modified Barthel Index (MBI) before and after treatment, and scanned with rs-fMRI to obtain amplitude of low-frequency fluctuation (ALFF). The patients with definite improvement were followed up with HAMD-17 through telephone four weeks after treatment. Results:There were three cases dropped down in each group. The scores of HAMD-17, PSQI and MBI improved in both groups (|t| > 11.446,P < 0.001), and improved more in the observation group than in the control group (|t| > 2.314, P < 0.05). ALFF of bilateral wedge lobe, bilateral lingual gyrus, right orbitofrontal cortex, right anterior cingulate gyrus and right middle temporal gyrus increased in the observation group, and it increased in the right lingual gyrus, right angular gyrus and lateral groove of right occipital lobe in the control group. A total of 29 patients were followed up successfully, and the HAMD-17 scores were still less than that before treatment (t > 13.558, P < 0.001). Conclusion:Music therapy can further alleviate depression under scalp acupuncture in patients with PSD for a long time after treatment, and improve sleep and activities of daily living, which may relate with the activation of the emotional circuit, such as orbitofrontal cortex and the middle temporal gyrus, and the primary visual cortex.

The changes in resting-state functional connectivity in stroke survivors with depression / 中华物理医学与康复杂志

Objective:To analyze any changes in the functional connectivity between the seed points of the dorsolateral prefrontal cortex (DLPFC) and the whole brain, as well as any fluctuations in the low-frequency amplitude among persons with post-stroke depression (PSD). The aim was to develop correlations among functional imaging results, clinical scales, and inflammation indicators including high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), interleukin 2 (IL-2), interleukin 10 (IL-10), interleukin 17a (IL-17a) and interferon-γ (IFN-γ).Methods:Between 2016 and 2020, 55 ischemic stroke survivors were tested. The 28 scoring 7 or more on the Hamilton Depression Scale (HAMD-17) formed the PSD group, while the 27 others formed the control group. Functional magnetic resonance images were collected, and serum inflammation indicators were determined.Results:When seed points in the left DLPFC were used, in the PSD group the frontal cortex (FC) decreased in one cluster, with a voxel of 129mm3 and the MNI coordinates (x=9, y=30, z=33) indicating that the anatomical automatic labeling (AAL) brain regions were the Cingulum_Ant_L, Cingulum_Mid_R and the frontal_Sup_Medial_L. When the right DLPFC was used as the seed point the FC again decreased in one cluster, with voxels of 44mm 3 and the MNI coordinates (x=-27, y=12, z=47) referring to the AAL brain region of the frontal_Mid_L. In the PSD group, the FC value of abnormal brain areas with the R-DLPFC as the seed point was positively correlated with time since stroke. In the control group, the FC value of abnormal brain areas with L-DLPFC as the seed point was negatively correlated with MoCA, while with R-DLPFC as the seed point it was positively correlated with IFN-γ. The FC values of abnormal areas of the brain showed no significant correlation with other clinical scales, inflammation indicators or lesion volume. Conclusion:Abnormal functional connections within the executive control network and between the salience networks may participate in the mechanism of PSD, and may be related to the time since stroke, cognitive functioning, and IFN-γ levels.