Alleviative effects of foraging exercise on depressive-like behaviors in chronic mild stress-induced ischemic rat model.

BACKGROUND: Poststroke depression (PSD) is a common complication that seriously affects the functional recovery and prognosis of an individual. As some patients with PSD fail to respond to drug therapy, it is urgent to find a viable alternative treatment. METHODS: An active exercise program known as foraging exercise (FE), using food as bait, was designed. First, focal ischemia and chronic unpredictable mild stress (CUMS) were used to establish a PSD model in rats. FE was then performed for 4 weeks. Body weight and behavioral assessments were conducted at the end of the 4th and 8th weeks. RESULTS: After 8 weeks, the results revealed that, compared with the PSD group, the behavioral scores of the rats in the PSD/FE group were significantly improved, the expression of Iba-1 in the affected frontal lobe and striatum was decreased, and serum levels of IL-6 and the IL-6/IL-10 ratio were downregulated. However, the ratio of residual brain volume in rats that had experienced CUMS was significantly less than that in the stroke group. CONCLUSION: FE can alleviate the behavioral scores of PSD rats, and its mechanism may be related to a modulation of the immune-inflammation response of microglia. Furthermore, chronic, persistent stress may increase the volume of cerebral infarction after stroke.

A Novel Balloon Catheter-based Dilation Intervention for Patients with Cricopharyngeus Achalasia After Stroke: A Randomized Study.

This study aimed to investigate the efficacy and safety of a novel balloon catheter in dilation intervention for patients with cricopharyngeus achalasia after stroke. Thirty-four patients with cricopharyngeus achalasia after stroke received routine swallowing rehabilitation training and were randomly assigned to an experimental group (Exp, n = 17) that received dilation therapy using the novel balloon catheter once daily for 5 days per week or a control group (Con, n = 17) that received dilation therapy with a 14-Fr ordinary urinary catheter once daily for 5 days per week. The intervention duration, Eating Assessment Tool (EAT)-10 scores, and Functional Oral Intake Scale (FOIS) scores were recorded at baseline and each day during intervention. The time for a patient's FOIS score to be ≥ 3 as well as the recovery time for oral intake of water, liquid food, mushy food, and solid food were recorded or estimated. Complications were also recorded during intervention. The intervention duration was shorter in the Exp group than in the Con group (p = 0.005). The Exp group patients improved faster than the Con group patients, with a shorter recovery time for oral intake of liquid food (p = 0.002), mushy food (p = 0.001), and solid food (p = 0.001). At the time of intervention termination, EAT-10 scores were lower in the Exp group than in the Con group (p = 0.005). The Exp group had a similar incidence of complications as the Con group but with better tolerability (p = 0.028). Compared with the urinary catheter, the novel balloon catheter for dilation in patients with cricopharyngeus achalasia after stroke may lead to a better and more rapid recovery.

ALKBH5 protects against stroke by reducing endoplasmic reticulum stress-dependent inflammation injury via the STAT5/PERK/EIF2α/CHOP signaling pathway in an m6A-YTHDF1-dependent manner.

BACKGROUND: Endoplasmic reticulum (ER) stress causes neuroinflammation and neuronal apoptosis during ischemic stroke progression. This study has investigated the role of ALKBH5 in ER stress during ischemic stroke progression. METHODS: In vivo and in vitro models of ischemic stroke were established by middle cerebral artery occlusion (MCAO) and OGD/R treatment, respectively. Cerebral infarct size was detected using triphenyltetrazolium chloride staining (TTC), and pathological changes were examined using histological staining. The levels of inflammatory factors were analyzed using Enzyme-linked immunosorbent assay. Cell counting kit-8 assay and flow cytometry were used to measure cell viability and apoptosis, respectively. The global m6A level was detected using the commercial kit, and STAT5 mRNA m6A level was determined using methylated RNA binding protein immunoprecipitation (Me-RIP). ALKBH5, YTHDF1, and STAT5 interactions were analyzed using RIP and RNA pull-down assays. RESULTS: ALKBH5 was upregulated in MCAO animals and OGD/R cell models. ALKBH5 knockdown exacerbated ER stress, neuroinflammation, and neuronal apoptosis in brain tissues and neuronal cells. ALKBH5 inhibited STAT5 mRNA stability and expression in an m6A-YTHDF1-dependent manner. STAT5 promoted ER stress by activating the PERK/eIF2/CHOP signaling pathway. Furthermore, STAT5 knockdown reversed the effects of ALKBH5 knockdown on OGD/R-induced ER stress and neuroinflammation in HT22 cells. CONCLUSION: ALKBH5 knockdown exacerbated ischemic stroke by increasing ER stress-dependent neuroinflammation and neuronal apoptosis via the STAT5/PERK/EIF2α/CHOP signaling pathway in an m6A-YTHDF1-dependent manner.

Altered Functional Connectivity of Amygdala with the Fronto-Limbic-Striatal Circuit in Temporal Lobe Lesion as a Proposed Mechanism for Poststroke Depression.

OBJECTIVE: Poststroke depression (PSD) is an important complication that affects stroke rehabilitation. Abnormal cortical-subcortical connectivity may be associated with the development of PSD. However, few studies have focused on the emotional network of PSD in the temporal lobe lesions. The aim of is study was to investigate amygdala-cortical functional connectivity (FC) in the temporal lobe in individuals with and without PSD. DESIGN: Twenty-three patients with PSD and 21 stroke patients without depression were recruited to undergo functional magnetic imaging scanning. RESULTS: In stroke patients with depression, the left amygdala had increased FC with the bilateral precuneus and right orbital frontal lobe but decreased FC with the right putamen. The right amygdala had increased FC with the right temporal pole, right rectus gyrus, and left orbital frontal lobe but decreased FC with the right primary sensory area (S1). Correlative analyses revealed that the amygdala's FCs with the right orbital frontal lobe, right insular cortex, and right cingulate cortex were correlated with the Hamilton Depression Rating Scale score. CONCLUSION: The current study identified mood affected through the fronto-limbic-striatal circuit in PSD. Hyperconnectivity between the amygdala, default mode network, and salience network might be related to depressive symptoms, which may provide novel insight into the underlying neuropathologic mechanisms of PSD in temporal lobe lesions.

Models of poststroke depression and assessments of core depressive symptoms in rodents: How to choose?

Our previous studies have indicated that depression and declined cognition have been involved in some neurodegenerative diseases including Stroke, Parkinson's diseases and Vascular Parkinsonism. Post-stroke depression (PSD) is the most common psychiatric disorder following a stroke and has high morbidity and mortality. Studies on PSD are increasingly common, but the specific mechanisms remain unknown. Current research mainly includes clinical and animal aspects. Questionnaires and peripheral blood examination are two of the most common methods used to study clinical PSD. The results of questionnaires are influenced by multiple factors such as disease history, education background, occupation, economic status, family relationships and social support. There are certain limitations to blood sample testing; for example, it is influenced by cerebrovascular diseases and some other disruptions of the internal environment. It is difficult for either method to fully clarify the pathophysiological mechanism of PSD. Animal models provide alternative methods to further understand the pathophysiological mechanisms of PSD, such as the involvement of neuronal circuits and cytokines. More than ten animal models of PSD have been developed, and new models are constantly being introduced. Therefore, it is important to choose the appropriate model for any given study. In this paper, we will discuss the characteristics of the different models of PSD and comment on the advantages and disadvantages of each model, drawing from research on model innovation. Finally, we briefly describe the current assessment methods for the core symptoms of PSD models, point out the shortcomings, and present the improved sucrose preference test as a rational evaluation of anhedonia.

Altered DMN functional connectivity and regional homogeneity in partial epilepsy patients: a seventy cases study.

PURPOSE: Clinically diagnosed partial epilepsy is hard to be functionally diagnosed by regular electroencephalograph (EEG) and conventional magnetic resonance imaging (MRI). By collecting transient brain regional signals, blood oxygenation level-dependent (BOLD) function MRI (BOLD-fMRI) can provide brain function change information with high accuracy. By using resting state BOLD-fMRI technique, we aim to investigate the changes of brain function in partial epilepsy patients. METHODS: BOLD-fMRI scanning was performed in 70 partial epilepsy and 70 healthy people. BOLD-fMRI data was analyzed by using the Regional Homogeneity (ReHo) method and functional connectivity of Default Mode Network (DMN) methods. The abnormal brain functional connectivity in partial epilepsy patients was detected by Statistical Parametric Mapping 8 (SPM8) analysis. RESULTS: Compared to healthy group, epilepsy patients showed significant decreased ReHo in left inferior parietal lobule/pre- and post-central gyrus, right thalamus/paracentral lobule/Cerebellum anterior and posterior Lobe, bilateral insula. The DMN functional connectivity regions decreased significantly in right uncus, left Inferior parietal lobule, left supramarginal gyrus, left uncus, left parahippocampa gyrus, and left superior temporal gyrus, in epilepsy patients, compared to healthy controls. SIGNIFICANCE: This study clarified that both ReHo and functional connectivity of DMN decreased in partial epilepsy patients compared to healthy controls. While left inferior parietal lobule was detected in both ReHo and DMN, many other identified regions were different by using these two BOLD-fMRI techniques. We propose that both ReHo and DMN patterns in BOLD-fMRI may suggest networks responsible for partial epilepsy genesis or progression.