BACKGROUND:High-density transcranial direct current stimulation (HD-tDCS) shows efficacy in major depressive disorder (MDD), but underlying mechanisms remain unclear. Electroencephalogram (EEG) microstates reflect large-scale network dynamics, and MDD patients exhibit microstate abnormalities. Whether HD-tDCS modulates these states and their clinical relevance is unknown. METHODS:In a randomized controlled trial, 39 MDD patients were assigned to either drug or HD-tDCS groups. The HD-tDCS group received accelerated stimulation over the left dorsolateral prefrontal cortex, twice daily for 20 sessions across two weeks, in addition to antidepressant medication. Resting-state EEG were recorded pre- and post-treatment, and microstate dynamics were analyzed in relation to symptom change. RESULTS:Both groups identified five microstates (A-E). The HD-tDCS group showed significantly greater reductions in Hamilton Depression Rating Scale (HAMD) scores, response rates, and remission rates compared with medication group. Only HD-tDCS induced significant microstate changes: decreased coverage of A and D, reduced duration of D, and decreased occurrence of E, alongside increased coverage and occurrence of B. In the remission subgroup, D coverage decreased and E coverage increased. Reduced D coverage correlated with Hamilton Anxiety Rating Scale (HAMA) improvement, increased B occurrence with HAMD improvement, and transitions from E to B with improvements on both scales. In remitters, changes in D coverage were strongly linked to reductions in both HAMA and HAMD. CONCLUSIONS:Microstate D and B were specifically associated with anxiety and depression improvement, respectively, while E to B transitions related to both. These findings provide novel neuro-electrophysiological evidence for accelerated HD-tDCS mechanisms in MDD.

Background: High-definition transcranial direct current stimulation (HD-tDCS) and repetitive transcranial magnetic stimulation (rTMS) demonstrate significant potential for improving depressive symptoms and cognitive function; however, their effectiveness varies greatly among individuals. Functional near-infrared spectroscopy enables real-time monitoring of brain function during cognitive tasks in patients with psychiatric disorders. Methods: A 4-week longitudinal study was conducted involving 61 patients with depression and 26 healthy controls. Patients were randomly assigned to HD-tDCS, rTMS, and antidepressant (AD) groups. Changes in depressive symptoms, adverse event rates, and prefrontal cortical oxyhemoglobin concentrations were assessed. Result: At week 4, remission rates were 62.5% (15), 61.9% (13), and 62.5% (10) in the HD-tDCS, rTMS, and AD groups, respectively (x2 = 0.002, p = 1.000). Response rates were 66.7% (16), 71.4% (15), and 68.8% (11), respectively, with no significant difference between groups (x2 = 0.12, p = 0.941). All groups demonstrated significant improvement in depressive symptoms and cognitive function. The rTMS group exhibited a significantly greater decrease in Hamilton Depression Scale score compared with the HDtDCS and AD groups. After 2 weeks of treatment, patients exhibited improved depressive symptoms and reduced activation during the verbal fluency task. However, these changes were not significantly correlated (r = -0.159 to 0.240, p = 0.121e0.988). Limitations: All patients had concomitant use of ADs, which may impact near-infrared spectroscopy signaling and have an indeterminate effect on cognition. Conclusion: HD-tDCS, rTMS, and ADs were equally effective, safe, and well-tolerated. HD-tDCS and rTMS were more effective for working memory, attention, executive functioning, and mood regulation. (c) 2025 The Authors. Published by Elsevier Ltd on behalf of Tsinghua University Press. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background rTMS is a safe and effective neuromodulation method for treating depression, but the specifics of its antidepressant effects and the underlying mechanisms remain uncertain. Methods Male SD rats were randomly divided into four groups: control group, CUMS group, CUMS + rTMS (10 Hz) group, and CUMS + celecoxib (25 mg/kg, as a positive control) group. Depression-like behavior was assessed by weight change, SPT, and FST; anxiety by OFT and EPM; and cognitive function by the Y-maze. WB, IF, ELISA, and qPCR were used to observe changes in COX-2/PGE2 signaling pathway-related proteins, inflammatory factors, and the activation of astrocytes and microglia in the hippocampus of rats. Results Compared to the control group, rats in the CUMS group exhibited significant anxiety-depression-like behavior and cognitive dysfunction. Compared to the CUMS group, rTMS and celecoxib interventions improved anxiety-depression-like behavior and cognitive dysfunction, reduced the expression of microglia and astrocytes, reversed the upregulation of pro-inflammatory factors (IL-1β, IL-6, TNF-α), and downregulated the expression of proteins related to the COX-2/PGE2 signaling pathway in CUMS-induced rats. Conclusions The study demonstrated that rTMS could improve anxiety-depression-like behavior and cognitive dysfunction in rats by modulating the COX-2/PGE2 pathway.

OBJECTIVE:To compare the clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) under facial feature point (FFP) localization versus neuro-navigated localization for depression. METHODS:42 depressed patients were randomly assigned to two groups, received 10 Hz rTMS twice daily for 10 consecutive days. Relevant symptom scale assessments were conducted by professionals at baseline, after 10 sessions, and at the end of treatment. The confidence interval was calculated at a 95 % confidence level. The significant level was set at p < 0.05. RESULTS:The absolute change in Hamilton Rating Scale for Depression (HAMD) total score from baseline to the end of therapy did not differ significantly between the groups. The generalized estimating equation showed the main effect of time was significant, which showed improvement of depressive symptoms in patients throughout treatment. Upon completion of the treatment, FFP group showed a response rate of 64.7 % and a remission rate of 29.4 %, whereas the navigated group exhibited a response rate of 61.1 % and a remission rate of 44.4 %. There was no serious adverse events occurred during the treatment process. Throughout the study, no intervention was made on the normal medication treatment, and some patients had concomitant antidepressants and benzodiazepines. CONCLUSION:There was no significant difference in clinical efficacy between FFP localization and navigated localization in the small-sample study. However, due to the limited sample size and lack of rigorous non-inferiority testing, the superiority of one over the other remains uncertain, necessitating rigorous experimental design to validate the efficacy difference between the two localization methods.

Post-stroke depression (PSD) is a common complication following a stroke, primarily characterized by low mood, cognitive sluggishness, and sleep disturbances. Currently, the precise pathogenic mechanisms underlying PSD remain elusive. Research indicates that S100B protein levels may serve as a specific biochemical marker of organic brain injury, with significantly elevated serum S100B levels noted in patients with ischemic stroke, depression, and schizophrenia. S100B facilitates apoptosis through various cellular signaling pathways and is implicated in inflammatory responses, thereby participating in the pathophysiology of numerous diseases. Nonetheless, the role of elevated S100B expression in PSD remains unclear. This study used a PSD rat model created by combining MCAO and CUMS to evaluate depressive behaviors. The expression of S100B and proteins associated with the PI3K/AKT/NF-κB signaling pathway was analyzed, while changes in inflammatory factors such as IL-1, IL-6, and TNF-α were quantified using ELISA. The findings demonstrated that the combination of MCAO and CUMS effectively induced depressive-like behaviors in the rats. In the PSD rat model, overexpression of S100B may inhibit the PI3K/AKT pathway and activate the NF-κB signaling pathway, thereby promoting the expression of inflammatory factors such as IL-1, IL-6, and TNF-α, which exacerbate brain tissue damage. However, the administration of S100B inhibitors improved depressive-like behaviors in PSD rats and reversed the alterations in the aforementioned signaling pathways and inflammatory factors. These findings advance the understanding of PSD pathogenesis and suggest therapeutic strategies.

Post-stroke depression (PSD) is the most common neuropsychiatric sequela of stroke, and its pathogenesis remains unclear. The blood-brain barrier (BBB) is an important barrier for maintaining the normal operation of neurons. The impairment of its function leads to the occurrence of various neurological diseases. Vascular endothelial growth factor A (VEGFA) is an important factor in regulating the permeability of the BBB. Its expression increases after stroke and aggravates brain injury. However, the role of VEGFA in PSD remains unclear. We used middle cerebral artery occlusion combined with shock to establish a PSD mouse model and evaluated the anxiety and depression-like behaviors of the mice through behavioral tests. The permeability of the BBB, the inflammatory response, and the expression levels of VEGFA and tight junction proteins in the hippocampus of PSD mice were detected. The results showed that middle cerebral artery occlusion combined with shock could lead to severe anxiety and depression-like behaviors in mice, and the increased expression of VEGFA led to BBB damage in PSD mice. Bevacizumab improved the permeability of the BBB, alleviated the inflammatory response in the hippocampus, and promoted neuronal repair in PSD mice by inhibiting VEGFA/VEGFR, thereby improving the depression-like behaviors of PSD mice. In conclusion, the above results indicate that VEGFA participates in the depression-like behaviors of PSD mice by regulating the permeability of the BBB.

Post-stroke depression (PSD) is a common psychiatric complication that occurs after stroke, especially in ischemic stroke (I/S). It has been reported that high-mobility group box-1 (HMGB1) is highly expressed in clinical PSD patients, but the exact molecular mechanism of its involvement in PSD is not completely clear, the neuroinflammation may participate in its development. Thus, we established a PSD rat model, observed behavioral and cognitive deficits, and found that the HMGB1/ receptor for advanced glycation end products (RAGE) pathway were activated in microglia. Glycyrrhizin acid (GA), an inhibitor of HMGB1, inhibited microglial activation, reversed the expression of HMGB1/RAGE, and ameliorated depressive-like behaviors in PSD rats. GA also reduced the expression of MAPK and NF-κB, which further led to decreased expression of IL-1β and NLRP3 inflammasome. These results suggested that the HMGB1/RAGE pathway was involved in microglial activation in the PSD model, promoting neuroinflammation and depressive-like behaviors.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a relatively common inherited arterial smooth muscle cell disease. The genetic defect is localized to the notch homolog protein 3 (NOTCH3) gene on chromosome 19q12 and is due to a missense variant in NOTCH3. The main clinical manifestations are transient ischemic attacks and repeated stroke, with cognitive impairments leading to dementia, migraine with aura, and mental/emotional disorders. To date, there is no specific therapeutic option, with only symptomatic supportive treatment for the symptoms of acute stroke, migraine, dementia, and mental abnormalities. Here, we provide a case report of a Chinese patient with CADASIL and a mutation in exon 4 of the NOTCH3 gene (p.Arg133Cys). The patient mainly exhibited recurrent cerebral infarction and affective disorder. Antidepressant treatment combined with repetitive transcranial magnetic stimulation significantly improved the depressive symptoms of the patient.

Background and objective Endoplasmic reticulum stress (ERS), as a primary defense mechanism against stress, is closely related to mental disorders, but its pathogenesis is still unclear. This research seeks to explore the influence of ERS-nucleotide-bound oligomerized domain-like receptor protein 3 (NLRP3) signaling on mice's depressive-like behaviors and cognitive impairment. Design and method We carried out a study on 32 male C57BL/6J mice to investigate how chronic unpredictable mild stress (CUMS) can give rise to depressive-like behaviors and cognitive dysfunction, randomly dividing them into control, model, inhibitor, and agonist groups. We utilized ELISA to quantify dopamine (DA) and 5-hydroxytryptamine (5-HT) levels. Using Nissl and hematoxylin and eosin (H&E) staining, we assessed the number and morphology of hippocampal neurons and cells. Western blot and immunofluorescence staining detected the changes in ERS and inflammation-related pathways in the hippocampus. Results CUMS could induce ERS and activate NLRP3 inflammasome, causing neuronal damage and histopathological changes, eventually leading to depressive-like behaviors and cognitive impairment in mice. The abnormal activation of NLRP3 inflammasome could be restored by ERS blocker 4-phenyl butyric acid (PBA), thus reducing neuronal damage, and ameliorating depressive-like behaviors and cognitive disorder in mice. Conclusion Our study demonstrates a previously unknown link between ERS and NLRP3 inflammasome in CUMS mice. The ERS-NLRP3 signaling pathway may be activated by CUMS, potentially resulting in mice exhibiting depressive-like behaviors and cognitive dysfunction. Theoretical foundations for elucidating the pathogenesis of depression, as well as its prevention and treatment, will be established through the results.

Background Breast cancer patients face significant psychological challenges, including difficulties in accepting the diagnosis, treatment, and long-term impact of the disease. Acceptance and Commitment Therapy (ACT) has shown promise in enhancing acceptance and psychological flexibility in various populations. This study aims to investigate the effectiveness of ACT in promoting disease acceptance among breast cancer patients through a randomized controlled trial. Methods This study will recruit 90 breast cancer patients and randomly allocate them to an ACT intervention or control group. The ACT intervention, focusing on acceptance, mindfulness, value clarification, and committed action, will be delivered over 4 weeks. Meanwhile, the control group will receive standard care with non-therapeutic intervention. The study’s primary outcome is disease acceptance, while secondary outcomes include depression, anxiety, social support, quality of life (QoL), and psychological inflexibility. Data will be collected at three points: baseline, post-intervention, and three-month follow-up. Statistical analysis will compare outcomes between groups to evaluate the effectiveness and mechanism of this intervention using covariance and mediation analysis. Discussion This study evaluates the effectiveness of ACT in promoting disease acceptance among breast cancer patients. It hypothesizes that the ACT group will show higher disease acceptance and improvements in social support, QoL, and psychological flexibility compared to the control group. The findings will contribute to research on psychological interventions and demonstrate ACT’s effectiveness in enhancing disease acceptance. Trial registration The research project is registered in the ClinicalTrials (NCT05327153).

Impaired glutamate recycling plays an important role in the pathophysiology of depression, and it has been demonstrated that glutamate transporter-1 (GLT-1) on astrocytes is involved in glutamate uptake. Studies have shown that repetitive transcranial magnetic stimulation (rTMS) is effective in treating depression, however, the exact mechanism of rTMS treatment remains unclear. Here, we used a chronic unpredictable mild stress (CUMS) protocol to induce depression-like behaviors in rats followed by rTMS treatment. Behavioral assessment was primarily through SPT, FST, OFT and body weight. Histological analysis focused on GFAP and GLT-1 expression, synaptic plasticity, apoptosis and PI3K/Akt/CREB pathway-related proteins. The results showed that rTMS treatment increased sucrose preference, improved locomotor activity, shortened immobility time as well as increased body weight. And rTMS intervention reversed the elevated glutamate concentration in the hippocampus of CUMS rats using an ELISA kit. Moreover, rTMS ameliorated the reduction in GFAP and GLT-1 expression, alleviated the decrease in BDNF, PSD95 and synapsin-1 expression, also reversed the expression levels of BAX and Bcl2 in the hippocampus of CUMS-induced rats. Moreover, rTMS also increased the protein phosphorylation level of PI3K/Akt/CREB pathway. These results suggest that rTMS treatment ameliorates depression-like behaviors in the rat model by reversing the reduction of GLT-1 on astrocytes and reducing glutamate accumulation in the synaptic cleft, which in turn ameliorates synaptic plasticity damage and neuronal apoptosis. The regulation of GLT-1 by rTMS may be through the PI3K/Akt/CREB pathway.

OBJECTIVE:Repetitive transcranial magnetic stimulation (rTMS) has recently emerged as a novel treatment option for patients with major depressive disorder (MDD), but clinical observations reveal variability in patient's responses to rTMS. Therefore, it is clinically significant to investigate the baseline neuroimaging differences between patients with (Responder) and without (NonResponder) response to rTMS treatment and predict rTMS treatment outcomes based on baseline neuroimaging data. METHOD:Baseline resting-state EEG data and Beck Depression Inventory (BDI) were collected from 74 rTMS Responder, 43 NonResponder, and 47 matched healthy controls (HC). EEG microstate analysis was applied to analyze common and differential microstate characteristics of Responder and NonResponder. In addition, the microstate temporal parameters were sent to four machine learning models to classify Responder from NonResponder. RESULT:There exists some common and differential EEG microstate characteristics for Responder and NonResponder. Specifically, compared to the HC group, both Responder and NonResponder exhibited a significant increase in the occurrence of microstate A. Only Responder showed an increase in the coverage of microstate A, occurrence of microstate D, transition probability (TP) from A to D, D to A, and C to A, and a decrease in the duration of microstates B and E, TP from A to B and C to B compared to HC. Only NonResponder exhibited a significant decrease in the duration of microstate D, TP from C to D, and an increase in the occurrence of microstate E, TP from C to E compared to HC. The primary differences between the Responder and NonResponder are that Responder had higher parameters for microstate D, TP from other microstates to D, and lower parameters for microstate E, TP from other microstates to E compared to NonResponder. Baseline parameters of microstate D showed significant correlation with Beck Depression Inventory (BDI) reduction rate. Additionally, these microstate features were sent to four machine learning models to predict rTMS treatment response and classification results indicate that an excellent predicting performance (accuracy = 97.35 %, precision = 96.31 %, recall = 100 %, F1 score = 98.06 %) was obtained when using AdaBoost model. These results suggest that baseline resting-state EEG microstate parameters could serve as robust indicators for predicting the effectiveness of rTMS treatment. CONCLUSION:This study reveals significant baseline EEG microstate differences between rTMS Responder, NonResponder, and healthy controls. Microstates D and E in baseline EEG can serve as potential biomarkers for predicting rTMS treatment outcomes in MDD patients. These findings may aid in identifying patients likely to respond to rTMS, optimizing treatment plans and reducing trial-and-error approaches in therapy selection.

Post-stroke depression (PSD) is a complication of cerebrovascular disease, which can increase mortality after stroke. CRH is one of the main signaling peptides released after activation of the hypothalamic-pituitary-adrenal (HPA) axis in response to stress. It affects synaptic plasticity by regulating inflammation, oxidative stress and autophagy in the central nervous system. And the loss of spines exacerbates depression-like behavior. Therefore, synaptic deficits induced by CRH may be related to post-stroke depression. However, the underlying mechanism remains unclear. The Keap1-Nrf2 complex is one of the core components of the antioxidant response. As an autophagy associated protein, p62 participates in the Keap1-NrF2 pathway through its Keap1 interaction domain. Oxidative stress is involved in the feedback regulation between Keap1-Nrf2 pathway and p62.However, whether the relationship between CRH and the Keap1-Nrf2-p62 pathway is involved in PSD remains unknown. This study found that serum levels of CRH in 22 patients with PSD were higher than those in healthy subjects. We used MCAO combined with CUMS single-cage SD rats to establish an animal model of PSD. Animal experiments showed that CRHR1 antagonist prevented synaptic loss in the hippocampus of PSD rats and alleviated depression-like behavior. CRH induced p62 accumulation in the prefrontal cortex of PSD rats through CRHR1. CRHR1 antagonist inhibited Keap1-Nrf2-p62 pathway by attenuating oxidative stress. In addition, we found that abnormal accumulation of p62 induces PSD. It alleviates depression-like behavior by inhibiting the expression of p62 and promoting the clearance of p62 in PSD rats. These findings can help explore the pathogenesis of PSD and design targeted treatments for PSD.

Post-stroke depression (PSD) is one of the most common mental sequelae after a stroke and can damage the brain. Although PSD has garnered increasing attention in recent years, the precise mechanism remains unclear. Studies have indicated that the expression of DAPK1 is elevated in various neurodegenerative conditions, including depression, ischemic stroke, and Alzheimer's disease. However, the specific molecular mechanism of DAPK1-mediated cognitive dysfunction and neuronal apoptosis in PSD rats is unclear. In this study, we established a rat model of PSD, and then assessed depression-like behaviors and cognitive dysfunction in rats using behavioral tests. In addition, we detected neuronal apoptosis and analyzed the expression of DAPK1 protein and proteins related to the ERK/CREB/BDNF signaling pathway. The findings revealed that MCAO combined with CUMS can induce more severe depression-like behaviors and cognitive dysfunction in rats, while overexpression of DAPK1 may hinder the downstream ERK/CREB/BDNF signaling pathways, resulting in neuronal loss and exacerbation of brain tissue damage. In this study, we will focus on DAPK1 and explore its role in PSD.

Hypertrophic olivary degeneration (HOD) arises from lesions of the dentato-rubro-olivary pathway (Guillain–Mollaret triangle), and bilateral HOD is the rarest. Our patient, a 42-year-old man with bilateral HOD caused by unilateral midbrain infarction, had both increased dizziness and ataxia as the first symptoms. HOD has no effective treatment and is easily misdiagnosed as other diseases in clinical practice. Our case demonstrated unique HOD symptomatology and emphasizes the important role of magnetic resonance imaging in diagnosing HOD. The use of gabapentin relieved nystagmus in our patient and may provide a reference for the future treatment of such patients.

Post-stroke depression (PSD) is a common neuropsychiatric complication of stroke, which seriously affects the quality of life and prognosis of patients. Nevertheless, the pathogenesis of PSD remains unclear. In our study, a PSD rat model was established by chronic restraint stress (CRS) combined with middle cerebral artery occlusion (MCAO). Depressive and anxiety-like behaviors were tested, as well as Neuronal loss and Apoptosis. The expression of synapse and p38 MAPK signaling pathway -relevant proteins was detected. Our data indicated that CRS combined with MCAO could induce depression-like and anxiety-like behaviors, which led to neuronal damage, apoptosis, and cellular loss in the left parietal cortex and left hippocampus. Furthermore, CRS combined with MCAO decreased synaptic plasticity in the parietal cortex and left hippocampus. We found that CRS combined with MCAO had activated the p38 MAPK signaling pathway, and decreased the expression of pathway-related proteins MKK6 and MKK3. These results suggested that CRS combined with MCAO could lead to depression-like behavior via neuronal damage, apoptosis and reduced synaptic plasticity, which might be related to the activation of the p38 MAPK pathway. Therefore, it provides novel ideas for the research on the intervention and prevention mechanisms of PSD.

Objective:To investigate the neuroprotective effect of synthetic triterpenoid(CDDO-Im)on ischemic stroke rats and its influence on inflammatory response by activating the nuclear factor 2-related factor 2(Nrf2)/antioxidant response elements(ARE)signaling pathway.Methods:SD rats were divided into sham group(S group),MCAO group(M group)and CDDO-Im inter-vention group(M+C group).The middle cerebral artery occlusion(MCAO)was used in M group and M+C group to establish ischemic stroke model in rats,and sham operation was used in S group to control.After operation,M+C group was injected with CDDO-Im(64 µg/300 g)every12 hours via caudal vein,S group and M group were given the same amount of normal saline.After 3 days,the nerve function of rats was measured by Longa score,and the area of cerebral infarction was evaluated by 2,3,5-triphenyltetrazolium chlo-ride(TTC)staining.The expressions of Nrf2,heme oxygenated-1(HO-1),ionic calcium binding adaptor molecule 1(Iba1),IL-1β and IL-4 protein were detected by Western blot.Results:Compared with S group,M group rats showed significant neurologic deficit and cerebral infarction area,and the expression of Nrf2 protein had no significant difference,and the expression levels of HO-1,Iba1,IL-1β and IL-4 protein were increased significantly(P<0.05).Compared with M group,the neurological deficit score,cerebral infarction area,the expression levels of Iba1 and IL-1β protein were decreased significantly(P<0.05),while Nrf2,HO-1 and IL-4 pro-tein expression increased significantly in M+C group(P<0.05).Conclusion:CDDO-Im may activate the Nrf2/ARE signaling pathway and play a neuroprotective role,which may be related to the modulation of microglia to M2 and the regulation of inflammatory response.

Stroke is a common nervous system disease with high incidence rate,mortality rate and disability rate.Hydrogen rich water is a type of drinking water containing high concentrations of hydrogen gas,which can be used to treat stroke.Hydrogen rich water mainly plays a role by reducing inflammatory reactions,cell apoptosis,oxidative stress reactions,etc.This article reviews the research progress on the therapeutic effect and mechanism of hydrogen rich water on stroke,in order to provide insights for the treatment plan of stroke.

Introduction: Post-stroke depression (PSD) is the most common emotional problem following a stroke. White matter hyperintensities (WMHs) are often reported in patients with a stroke, and are often divided into deep WMHs (DWMHs) and periventricular WMHs (PVWMHs). The relationship between WMHs and PSD remains controversial. This review aims to resolve this controversy.Methods: A systematic search of electronic databases was conducted for studies. We extracted the relevant data and evaluated the study quality by using the Newcastle-Ottawa Scale. We pooled odds ratios (OR) for the same type of WMHs that were present in the relevant PSD period.Results: 15 studies (n = 4133 patients) met our inclusion criteria. In the acute phase, WMHs, DWMHs, severe WMHs, and severe DWMHs were not significant risk factors for incident depression, but PVWMHs (pooled OR, 1.21; 95 % CI, 1.01-1.44) and severe PVWMHs (pooled OR, 1.72; 95 % CI, 1.12-2.65) had a significant asso-ciation with PSD. In the subacute phase, DWMHs, DWMHs, and severe WMHs were not significantly associated with PSD, but PVWMHs (pooled OR, 2.44; 95 % CI, 1.25-4.76) showed a significant association with PSD. In the chronic phase, severe PVWMHs had no significant association with PSD, while WMHs (pooled OR, 1.063; 95 % CI, 1.03-1.09), DWMHs (pooled OR, 1.40; 95 % CI, 1.11-1.76), PVWMHs (pooled OR, 1.28; 95 % CI, 1.11-1.48), and severe DWMHs (pooled OR, 1.52; 95 % CI, 1.12-2.05) showed a significant association with PSD.Conclusion: We found a significant association between WMHs/DWMHs/PVWMHs and PSD in the chronic post -stroke phase. PVWMHs had a stronger correlation with PSD in each period after stroke than WMHs and DWMHs. High-quality prospective studies are still needed to fully resolve this relationship.

Repetitive transcranial magnetic stimulation (rTMS) is a novel non-invasive neuromodulation technique with neuroprotective properties and is used to treat depression. However, the underlying mechanism of action remains unclear. In this study, we examined the possible mechanism mediating the antidepressant effect of rTMS using animal experiments. Specific pathogen-free rats were treated with rTMS after exposure to social isolation combined with chronic unpredictable mild stress (CUMS). After four weeks of CUMS, the rats exhibited a significant decrease in spatial working memory assessed using open-field testing, a general loss of interest assessed with the sucrose preference test, and a significant reduction in spatial recognition memory ability assessed using the Y-maze. These behavioral deficits were accompanied by decreased numbers of astrocytes in the hippocampus, decreased expression of glial fibrillary acidic protein (GFAP), increased numbers of neural stem cells (NSCs), and increased expression of nestin protein. These results indicated that neuron damage occurred in the depression-like rats. After rTMS intervention, the depression-like behavior was alleviated significantly, and the numbers of NSCs and astrocytes, as well as the expression of GFAP and nestin proteins, returned to normal levels. Overall, it is likely that attenuation of NSC proliferation and differentiation into astrocytes produced a neuroprotective effect on hippocampal neurons, which might partly explain the mechanism by which rTMS alleviates depression.