CRHR1 antagonist alleviated depression-like behavior by downregulating p62 in a rat model of post-stroke depression.

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.

DAPK1 mediates cognitive dysfunction and neuronal apoptosis in PSD rats through the ERK/CREB/BDNF signaling pathway.

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.

High-frequency repetitive transcranial magnetic stimulation improves depressive-like behaviors in CUMS-induced rats by modulating astrocyte GLT-1 to reduce glutamate toxicity.

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.

White matter hyperintensities and post-stroke depression: A systematic review and meta-analysis.

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 association 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.

CRS induces depression-like behavior after MCAO in rats possibly by activating p38 MAPK.

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.

Repetitive Transcranial Magnetic Stimulation Improves Depression-like Behavior in Rats by Promoting Neural Stem Cell Proliferation and Differentiation.

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.

Reduced Gray Matter Volume in Orbitofrontal Cortex Across Schizophrenia, Major Depressive Disorder, and Bipolar Disorder: A Comparative Imaging Study.

Schizophrenia (SZ), major depressive disorder (MDD), and bipolar disorder (BD) are severe psychiatric disorders and share common characteristics not only in clinical symptoms but also in neuroimaging. The purpose of this study was to examine common and specific neuroanatomical features in individuals with these three psychiatric conditions. In this study, 70 patients with SZ, 85 patients with MDD, 42 patients with BD, and 95 healthy controls (HCs) were recruited. Voxel-based morphometry (VBM) analysis was used to explore brain imaging characteristics. Psychopathology was assessed using the Beck Depression Inventory (BDI), the Beck Anxiety Inventory (BAI), the Young Mania Rating Scale (YMRS), and the Positive and Negative Syndrome Scale (PANSS). Cognition was assessed using the digit symbol substitution test (DSST), forward-digital span (DS), backward-DS, and semantic fluency. Common reduced gray matter volume (GMV) in the orbitofrontal cortex (OFC) region was found across the SZ, MDD, and BD. Specific reduced GMV of brain regions was also found. For patients with SZ, we found reduced GMV in the frontal lobe, temporal pole, occipital lobe, thalamus, hippocampus, and cerebellum. For patients with MDD, we found reduced GMV in the frontal and temporal lobes, insular cortex, and occipital regions. Patients with BD had reduced GMV in the medial OFC, inferior temporal and fusiform regions, insular cortex, hippocampus, and cerebellum. Furthermore, the OFC GMV was correlated with processing speed as assessed with the DSST across four groups (r = 0.17, p = 0.004) and correlated with the PANSS positive symptoms sub-score in patients with SZ (r = - 0.27, p = 0.026). In conclusion, common OFC alterations in SZ, MDD, and BD provided evidence that this region dysregulation may play a critical role in the pathophysiology of these three psychiatric disorders.

High-frequency repetitive transcranial magnetic stimulation mitigates depression-like behaviors in CUMS-induced rats via FGF2/FGFR1/p-ERK signaling pathway.

High-frequency repetitive transcranial magnetic stimulation (rTMS) is a widely used and effective biological treatment for depression. Although previous studies have shown that astrocyte function may be modified by rTMS, the specific neurobiological mechanisms underlying its antidepressant action are not clear. Substantial evidence has accumulated indicating that neurotrophin dysfunction and neuronal apoptosis play a role in the development of depression. To evaluate this hypothesis, we applied a chronical unpredictable mild stress (CUMS) protocol to induce depression-like behaviors in rats, followed by the delivery of 10-Hz rTMS for 3 weeks. Behavioral outcome measures consisted of a sucrose preference test, forced swimming test, and open field test. Histological analysis focused on apoptosis, expression of GFAP and FGF2, and FGF2 pathway-related proteins. The results showed that after rTMS treatment, the rats' sucrose preference increased, open field performance improved while the immobility time of forced swimming decreased. The behavioral changes seen in rTMS treated rats were accompanied by marked reductions in the number of TUNEL-positive neural cells and the level of expression of BAX and by an increase in Bcl2. Furthermore, the expression of GFAP and FGF2 was increased, along with activation of FGF2 downstream pathway. These results suggest that rTMS treatment can improve depression-like behavior, attenuate neural apoptosis, and reverse reduction of astrocytes in a rat model of depression. We hypothesize that the therapeutic action of rTMS in CUMS-induced rats is linked to the activation of the FGF2/FGFR1/p-ERK signaling pathway.

Serum vaspin as a predictor of severity and prognosis in acute ischemic stroke patients.

Objective: The influence of vaspin on vascular health had been investigated, yielding conflicting results. This study is intended to investigate the relation between vaspin and stroke severity and stroke outcome in a cohort Chinese patient with acute ischemic stroke (AIS).Methods: This was a prospective single-center observational study in Xinxiang, China. From 1 July 2017 to 30 November 2019, all patients with first-ever AIS were consecutively included. Serum levels of vaspin, stroke severity at (assessed by NIHSS score) admission and functional outcome (assessed by modified Rankin Scale (mRS)) at discharge were recorded. Multivariate analyses were assessed using logistic regression models.Results: Finally, 340 patients with AIS were included. The median age of those patients was 65 (interquartile range [IQR], 56-74) years and 61.8% were men. At admission, 88 patients (25.9%) experienced severe stroke (NIHSS>10) and serum levels of vaspin (median [IQR]: 0.72[0.48-0.90]ng/ml) in those patients were significantly lower than in those mild(0.92[0.70-1.19]ng/ml) and moderate stroke (0.93[0.63-1.21]ng/ml). At discharge, 113 patients (33.2%) experienced poor functional outcome (mRS >2) and vaspin serum levels in those patients were lower as compared with patients who experienced good outcome (0.71[0.45-0.98] vs. 0.91[0.71-1.19]ng/ml). In multivariate analyses, lower level of vaspin (< median) was associated with a 2.5-fold (odds ratio [OR] 2.46; 95% confidence interval [CI]: 1.75-4.45) increased risk for severe stroke and a 2.1-fold (2.03; 1.42-3.58) increased risk for poor outcome.Conclusion: In conclusion, reduced serum levels of vaspin at admission are significantly related to stroke severity and prognosis, which illustrates a predictive role of reduced vaspin in ischemic stroke.

Contribution of AMPA Receptor-Mediated LTD in LA/BLA-CeA Pathway to Comorbid Aversive and Depressive Symptoms in Neuropathic Pain.

Comorbid anxiety and depressive symptoms in chronic pain are a common health problem, but the underlying mechanisms remain unclear. Previously, we have demonstrated that sensitization of the CeA neurons via decreased GABAergic inhibition contributes to anxiety-like behaviors in neuropathic pain rats. In this study, by using male Sprague Dawley rats, we reported that the CeA plays a key role in processing both sensory and negative emotional-affective components of neuropathic pain. Bilateral electrolytic lesions of CeA, but not lateral/basolateral nucleus of the amygdala (LA/BLA), abrogated both pain hypersensitivity and aversive and depressive symptoms of neuropathic rats induced by spinal nerve ligation (SNL). Moreover, SNL rats showed structural and functional neuroplasticity manifested as reduced dendritic spines on the CeA neurons and enhanced LTD at the LA/BLA-CeA synapse. Disruption of GluA2-containing AMPAR trafficking and endocytosis from synapses using synthetic peptides, either pep2-EVKI or Tat-GluA2(3Y), restored the enhanced LTD at the LA/BLA-CeA synapse, and alleviated the mechanical allodynia and comorbid aversive and depressive symptoms in neuropathic rats, indicating that the endocytosis of GluA2-containing AMPARs from synapses is probably involved in the LTD at the LA/BLA-CeA synapse and the comorbid aversive and depressive symptoms in neuropathic pain in SNL-operated rats. These data provide a novel mechanism for elucidating comorbid aversive and depressive symptoms in neuropathic pain and highlight that structural and functional neuroplasticity in the amygdala may be important as a promising therapeutic target for comorbid negative emotional-affective disorders in chronic pain.SIGNIFICANCE STATEMENT Several studies have demonstrated the high comorbidity of negative affective disorders in patients with chronic pain. Understanding the affective aspects related to chronic pain may facilitate the development of novel therapies for more effective management. Here, we unravel that the CeA plays a key role in processing both sensory and negative emotional-affective components of neuropathic pain, and LTD at the amygdaloid LA/BLA-CeA synapse mediated by GluA2-containing AMPAR endocytosis underlies the comorbid aversive and depressive symptoms in neuropathic pain. This study provides a novel mechanism for elucidating comorbid aversive and depressive symptoms in neuropathic pain and highlights that structural and functional neuroplasticity in the amygdala may be important as a promising therapeutic target for comorbid negative emotional-affective disorders in chronic pain.

CDDO-Im exerts antidepressant-like effects via the Nrf2/ARE pathway in a rat model of post-stroke depression.

Increasing evidence suggests that oxidative damage and neuroinflammation play a critical role in the pathogenesis of post-stroke depression (PSD). These pathologic processes are tightly regulated by the NF-E2-related factor 2/antioxidant response element (Nrf2/ARE) signaling pathway. The synthetic triterpenoid, 2-Cyano-3,12-dioxooleana-1,9-dien-28-imidazolide (CDDO-Im), is a potent Nrf2 activator. This study investigated whether CDDO-Im exhibited antidepressant-like activity and elucidated its protective mechanisms in a rat model of PSD, which was produced by middle cerebral artery occlusion (MCAO) followed by 28 days of chronic unpredictable mild stress (CUMS) in conjunction with solitary housing. The results demonstrated that CDDO-Im treatment markedly improved the depressive-like behaviors and reduced neuronal cell loss in the hippocampus, through decreasing the malondialdehyde (MDA) content (indicative of lipid peroxidation), superoxide dismutase (SOD), NF-kB activation, interleukin-6 (IL-6) and interleukin-1b (IL-1ß) in PSD rats. CDDO-Im treatment alleviated the oxidative stress and inflammatory response in PSD rats by promoting Nrf2 nuclear import and increasing the protein levels of Nrf2 downstream target genes, including heme oxygenase-1(HOMX1) and, quinone oxidoreductase-1(NQO1).These findings suggested that CDDO-Im treatment exhibited antidepressant-like effects and protected PSD rats from oxidative and inflammatory injury via the Nrf2/ARE pathway. Therefore, CDDO-Im treatment is worthy of further study.

Clinical Features of Trousseau Syndrome With Cerebral Infarction as the Initial Manifestation.

OBJECTIVE: There are few reports of Trousseau syndrome with cerebral infarction as the initial manifestation before the discovery of the tumor, which is often missed and misdiagnosed, and there is no unified therapy. To explore the clinical features of the Trousseau syndrome and, among those features, the risk factors for cerebral infarction as the initial manifestation. METHODS: This was a retrospective study of 416 consecutive patients with cerebral infarction and malignant tumor admitted at The First Affiliated Hospital of Xinxiang Medical University between January 2015 and December 2017. The patients were grouped as: (1) cerebral infarction as the initial manifestation; and (2) tumor as the initial manifestation. A multivariable logistic regression analysis was used to analyze the relationship between the clinical features (age, sex, characteristics of the infarction, characteristics of the tumors, treatments, depression, coagulopathy, The National Institute of Health stroke scale score, platelet count, red cell count, hemoglobin, atherosclerosis, and coagulation parameters) and the hypercoagulable state. RESULTS: A total of 416 patients met the criteria were included: 212 (51.0%) in the group with cerebral infarction as the initial manifestation and 204 (49.0%) in the group with tumor as the initial manifestation. The multivariable analysis showed that metastatic cancer (odds ratio=2.517; 95% confidence interval, 1.193-5.311; P=0.015) and depressive state (odds ratio=3.158; 95% confidence interval, 1.522-6.551; P=0.002) were independently associated with the Trousseau syndrome with cerebral infarction as the main manifestation. CONCLUSIONS: Trousseau syndrome with cerebral infarction as the initial manifestation was associated with metastatic cancer and depressive state. There was no difference in coagulation status between the 2 groups.

Neuroprotective Effects of Umbilical Cord-Derived Mesenchymal Stem Cells on Radiation-Induced Brain Injury in Mice.

OBJECTIVE: To investigate the neuroprotective effects of umbilical cord-derived mesenchymal stem cells (UC-MSCs) on radiation-induced brain injury (RIBI). METHODS: Thirty female C57BL/6 mice were randomly divided into three groups: control (CON), whole brain irradiation (WBI), and the cell therapy (MSC) group. Mice in the WBI and MSC groups received a single, whole brain irradiation treatment with 15 Gy of 60Co. Learning and memory were evaluated in the mice using the step-down avoidance test. The neuronal changes in the hippocampal cornu ammonis (CA) 1 region were observed using hematoxylin eosin (H&E) staining. The changes in astrocytes were visualized with glial fibrillary acidic protein immunohistochemistry, and the expression of TNF-α, IL-6, and IL-10 was detected by quantitative polymerase chain reaction (qPCR) along with Enzyme linked immunosorbent assay (ELISA). RESULTS: Compared with mice in the WBI group, learning and memory in the MSC mice were significantly increased (P<0.05), neuronal degeneration and necrosis were significantly decreased (P<0.05), and the number of astrocytes was significantly increased (P<0.05). The levels of the in˙ammatory cytokines, TNF-α and IL-6, were significantly decreased (P<0.05), however, the inhibitory factor IL-10 was significantly increased (P<0.05). CONCLUSIONS: UC-MSCs play a neuroprotective role by inhibiting brain cell injury and neuroinflammation.

Plasma levels of ceramides relate to ischemic stroke risk and clinical severity.

Recent studies have suggested that specific plasma ceramides are independently associated with atherosclerosis and cardiovascular diseases, but it is currently unknown whether plasma ceramide levels are associated with ischemic stroke. Here, we examined whether ceramides were associated with both ischemic stroke risk and clinical severity at admission. We measured three previously identified high-risk plasma ceramide molecules [Cer(d18:1/16:0), Cer(d18:1/22:0), and Cer(d18:1/24:0)] in 202 patients with acute ischemic stroke and 202 age and sex matched control cases. Plasma ceramides levels were measured by a targeted liquid chromatography-tandem mass spectrometry assay at baseline. The median age of the 202 stroke patients was 66 (interquartile range [IQR], 58-75) years and 54.0 % were men. Plasma levels of C16:0, C22:0, and C24:0 ceramides in stroke patients were significantly higher than in those control cases (P < 0.001, all). In multivariate logistic regression analysis adjusted for other risk factors, higher levels of C16:0, C22:0, and C24:0 ceramides were associated with higher risk of ischemic stroke (odd ratio [OR] for one IQR increase: 2.15[1.42-2.99]; 2.90[2.13-4.01] and 1.29[1.10-1.69]; respectively). At admission, 103 patients (51.0 %) had a minor stroke (NIHSS < 6). In these patients, plasma levels of C16:0, C22:0, and C24:0 ceramides were lower than that observed in patients with moderate-to-high clinical severity (P < 0.001, all). In multivariate logistic regression analysis adjusted for other risk factors, higher levels of C16:0, C22:0, and C24:0 ceramides were associated with higher risk of moderate-to-high stroke (OR for one IQR increase: 2.96 [2.05-4.22], 3.03 [2.01-4.25] and 1.72 [1.25-3.31], respectively). An elevated plasma levels of ceramides were predictors of both risk and severity at admission in ischemic stroke patients. The underlying mechanisms of these associations remain to be investigated.

The physiological modulation by intracellular kinases of hippocampal γ-oscillation in vitro.

Hippocampal network oscillations at gamma frequency band (γ-oscillation, 20-80 Hz) are synchronized synaptic activities generated by the interactions between the excitatory and inhibitory interneurons and are associated with higher brain function such as learning and memory. Despite extensive studies about the modulation of intracellular kinases on synaptic transmission and plasticity, little is known about the effects of these kinases on γ-oscillations. In this study, we examined the effects of several critical intracellular kinases such as cyclic AMP-dependent protein kinase (PKA), protein kinase B (PKB)/Akt, protein kinase C (PKC), extracellular-regulated protein kinases (ERK) and AMP-activated protein kinase (AMPK), known to regulate synaptic transmission, on hippocampal γ-oscillations in vitro. We found that AMPK inhibitor but not PKA, PKC, or ERK inhibitor, strongly enhanced the power of γ-oscillation (γ-power) and that Akt inhibitor weakly increased γ-power. Western blot analysis confirmed that AMPK inhibitor reduced the expression of p-AMPK but not total AMPK. By using the slice whole cell voltage-clamp technique, we found that AMPK inhibitor increased the frequency but not amplitude of spontaneous inhibitory postsynaptic currents (sIPSC) and had no effect on either frequency or amplitude of spontaneous excitatory postsynaptic currents (sEPSC). Therefore, AMPK activation negatively modulates hippocampal γ-oscillation via modulation of the inhibitory neurons.

The Safety and Efficacy of Mechanical Thrombectomy in Posterior VS. Anterior Emergent Large Vessel Occlusion: A Systematic Review and Meta-analysis.

BACKGROUND AND PURPOSE: Currently, mechanical thrombectomy (MT) for emergent large-vessel occlusion (ELVO) has been widely used in the clinic. However, the question about whether MT provides the same benefits between posterior circulation emergent large vessel occlusion (pc-ELVO) and anterior emergent large vessel occlusion (ac-ELVO) remains unclear. MATERIAL AND METHODS: We conducted a systematic review and meta-analysis of 11 studies published between 2011 and 2019 through searching the PubMed, EMBASE, and Cochrane Library. Major clinical outcomes include: (1) favorable functional outcome at 90 days; (2) symptomatic intracerebral hemorrhage (sICH); (3) mortality and; (4) successful recanalization rate. RESULTS: Eleven of 4637 studies met our pre-established inclusion criterion, comprising 4619 patients. In primary analysis, MT in patients with pc-ELVO in comparison to patients with ac-ELVO had a lower likelihood of sICH (odds ratio [OR] = .48; [95% confidence interval (CI), .26-.88]; P = .02) but a higher likelihood of mortality (OR = 1.98; [95% CI, 1.37-2.87]; P = .0003). The pooled evidence indicated that patients with pc-ELVO had worse functional outcome than patients with ac-ELVO in the large sample size group (OR = .79; [95% CI, .63-.98]; P = .03). In addition, no statistical significance was found in the outcome of successful recanalization rate (OR = 1.12; [95% CI, .88-1.42]; P = .35). CONCLUSIONS: Our results showed that patients with pc-ELVO receiving MT reduced the risk of sICH but seemed to be associated with poor prognosis.

Upregulation of aryl hydrocarbon receptor nuclear translocator 2 in the hippocampi of post-stroke depression rats.

Aryl hydrocarbon receptor nuclear translocator protein 2 (ARNT2), a member of the basic helix-loop-helix superfamily of transcription factors, may serve a vital role in neuronal survival and cell proliferation via formation of heterodimers with hypoxia-inducible factor-1α. Previous studies indicated that ARNT2 levels were elevated in the brains of ischemic rats; however, the involvement of ARNT2 in post-stroke depression (PSD) rats is not well understood. Therefore, the present study aimed to investigate the levels of ARNT2 in the hippocampi of PSD rats, and to clarify the potential association between ARNT2 and behavioral performance. A PSD rat model was established by middle cerebral artery occlusion (MCAO) followed by a 4-week chronic unpredictable mild stress (CUMS) regimen. A sucrose preference test and open field test (OFT) were conducted, and body weight was measured. In addition, reverse transcription-polymerase chain reaction and immunohistochemistry were performed to measure ARNT expression. Results indicated that MCAO+CUMS rats had lower weight gain, consumed less sucrose and moved less compared with controls. Furthermore, the mRNA and protein levels of ARNT in MCAO+CUMS rats were increased compared with in controls. The sucrose preference index and horizontal movement distance in the OFT were positively correlated with ARNT mRNA level. Thus, from these findings it was suggested that ARNT2 may be positively associated with improvement of cognitive impairment, and therefore may be a potential target in PSD treatment.

Association between PDE4D polymorphism and ischemic stroke in young population.

OBJECTIVE: To explore the association between the polymorphisms of the phosphodiesterase (PDE) 4D gene (SNP83 and SNP87) and the risk of ischemic stroke (IS) in Chinese young population. METHODS: This study included 393 patients who were divided into IS group and non-IS group. Semiconductor high-throughput sequencing technology and multivariate logistic regression analysis were performed. RESULTS: In the case group, the frequency of CC genotype and C allele of the SNP83 gene was significantly higher than that in the control group. There was no significant difference in genotype frequency distribution of SNP87 between the two groups. CONCLUSION: We found an association between SNP83 and the risk of IS in Chinese young population from northern Henan province. There was not a significant association between SNP87 and IS in Chinese young population.

rTMS ameliorated depressive-like behaviors by restoring HPA axis balance and prohibiting hippocampal neuron apoptosis in a rat model of depression.

Repetitive transcranial magnetic stimulation (rTMS) has been widely used to treat depression. The mechanistic basis for the effects of rTMS is not well understood, although previous studies have suggested that it involves the regulation of hypothalamic-pituitary-adrenocortical (HPA) axis and protection of hippocampal neurons. We investigated this in the present study using a chronic unpredictable mild stress (CUMS) paradigm in Sprague-Dawley rats. The rats were subjected to rTMS for 15 consecutive days, and body weight, sucrose consumption, and locomotor activity were evaluated. B cell lymphoma-2-associated X protein (Bax) expression was assessed by immunohistochemistry; cell morphology was examined by Nissl staining; and adrenocorticotropic hormone (ACTH) and cortisol (CORT) levels in the hippocampus were measured by enzyme-linked immunosorbent assay. CUMS decreased body weight and sucrose consumption in rats along with horizontal/vertical distance traveled in the open field test. Rats subjected to CUMS also showed increased levels of Bax as well as ACTH and CORT; the hippocampal neurons in these animals had abnormal morphology and were reduced in number. rTMS reversed these changes and improved depression-like behaviors. Thus, rTMS abrogates the loss of hippocampal neurons and restores the balance of the HPA axis in the treatment of depression.

N-Butylphthalide (NBP) ameliorated cerebral ischemia reperfusion-induced brain injury via HGF-regulated TLR4/NF-κB signaling pathway.

N-Butylphthalide (NBP) has been known to have potential neuroprotective effects in Alzheimer's disease and stroke animal models. Hepatocyte-growth factor (HGF), with strong angiogenic properties, exerted protective role in brain injury. The present study was aimed to investigate the possible anti-inflammatory effects of NBP on the brain injury of rats with cerebral ischemia reperfusion (IR) and astrocytes activation induced by lipopolysaccharide (LPS) treatment. Our results showed that cerebral IR induced brain damage with down-regulation of HGF and astrocytes activation. NBP treatment significantly increased HGF expression and activated cMet/PI3K/AKT signaling pathway, stimulating mTOR activity and suppressing apoptosis in brain tissues. Also NBP inhibited pro-inflammatory cytokines expression, including IL-6, IL-1ß, and TNFα, via TLR4/NF-κB suppression. Anti-HGF treatment enhanced TLR4 expression while HGF could suppress TLR4 activation and its down-streaming signals, attenuating inflammation finally. Notably, NBP up-regulated HGF and down-regulated TLR4 expression significantly in the astrocytes combined with the treatment of TLR4 inhibitor than the cells only treated with TLR4 inhibitor, suggesting that NBP could further suppress TLR4 activation, suggesting that NBP might impede TLR4 through up-regulating HGF expression. These results suggested that NBP treatment significantly ameliorated cerebral IR-induced brain injury by inhibiting TLR4/NF-κB-associated inflammation regulated by HGF.