Transcranial focused ultrasound stimulation alleviates NLRP3-related neuroinflammation induced by ischemic stroke via regulation of the Nespas/miR-383-3p/SHP2 pathway.

Transcranial focused ultrasound stimulation (tFUS) has emerged as a promising therapeutic strategy for mitigating brain injury in animal models. In this study, the effects and mechanisms of tFUS on ischemic stroke were explored in a transient middle cerebral artery occlusion (MCAO) rat model. Low-intensity tFUS was administered to the ischemic hemisphere 24 h post-MCAO for seven consecutive days.

Activation of Hippocampal Neuronal NADPH Oxidase NOX2 Promotes Depressive-Like Behaviour and Cognition Deficits in Chronic Restraint Stress Mouse Model.

Background: Nicotinamide adenosine dinucleotide phosphate oxidases (NOX) play important roles in mediating stress-induced depression. Three NOX isotypes are expressed mainly in the brain: NOX2, NOX3 and NOX4. In this study, the expression and cellular sources of these NOX isoforms was investigated in the context of stress-induced depression.

Physical exercise-induced circAnks1b upregulation promotes protective endoplasmic reticulum stress and suppresses apoptosis via miR-130b-5p/Pak2 signaling in an ischemic stroke model.

Aims: Physical exercise (PE) can accelerate post-stroke recovery. This study investigated contributions of circRNAs to PE-induced improvements in post-stroke neurological function.

Methods: Rats subjected to transient middle cerebral artery occlusion were left sedentary or provided running-wheel access for 4 weeks during recovery.

Influenza Vaccination Mediates SARS-CoV-2 Spike Protein Peptide-Induced Inflammatory Response via Modification of Histone Acetylation.

The effectiveness of coronavirus disease 2019 (COVID-19) vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain rapidly wanes over time. Growing evidence from epidemiological studies suggests that influenza vaccination is associated with a reduction in the risk of SARS-CoV-2 infection and COVID-19 severity. However, the underlying mechanisms remain elusive.

Blood Brain Barrier-Crossing Delivery of Felodipine Nanodrug Ameliorates Anxiety-Like Behavior and Cognitive Impairment in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder leading to cognitive decline. Excessive cytosolic calcium (Ca) accumulation plays a critical role in the pathogenesis of AD since it activates the NOD-like receptor family, pyrin domain containing 3 (NLRP3), switches the endoplasmic reticulum (ER) unfolded protein response (UPR) toward proapoptotic signaling and promotes Aβ seeding. Herein, a liposomal nanodrug (felodipine@LND) is developed incorporating a calcium channel antagonist felodipine for Alzheimer's disease treatment through a low-intensity pulse ultrasound (LIPUS) irradiation-assisted blood brain barrier (BBB)-crossing drug delivery.

Voluntary wheel exercise improves glymphatic clearance and ameliorates colitis-associated cognitive impairment in aged mice by inhibiting TRPV4-induced astrocytic calcium activity.

Background And Objectives: Chronic colitis exacerbates neuroinflammation, contributing to cognitive impairment during aging, but the mechanism remains unclear. The polarity distribution of astrocytic aquaporin 4 (AQP4) is crucial for the glymphatic system, which is responsible for metabolite clearance in the brain. Physical exercise (PE) improves cognition in the aged.

Exercise pretreatment alleviates neuroinflammation and oxidative stress by TFEB-mediated autophagic flux in mice with ischemic stroke.

Background: Neuroinflammation and oxidative stress are important pathological mechanisms underlying cerebral ischemic stroke. Increasing evidence suggests that regulation autophagy in ischemic stroke may improve neurological functions. In this study, we aimed to explore whether exercise pretreatment attenuates neuroinflammation and oxidative stress in ischemic stroke by improving autophagic flux.

Bacille Calmette-Guérin attenuates vascular amyloid pathology and maximizes synaptic preservation in APP/PS1 mice following active amyloid-β immunotherapy.

Despite effective clearance of parenchymal amyloid-β (Aβ) in patients with Alzheimer's disease, Aβ immunotherapy exacerbates the vascular Aβ (VAβ)-associated pathology in the brain. We have previously shown that BCG immunization facilitates protective monocyte recruitment to the brain of APP/PS1 mice. Here, we confirmed that the 4Aβ1-15 vaccine exacerbates VAβ deposits in this model, which coincides with a decrease in the number of cerebrovascular endothelial cells and pericytes, infiltration of neutrophils into the brain, and induction of cerebral microhemorrhage.

Influenza vaccine combined with moderate-dose PD1 blockade reduces amyloid-β accumulation and improves cognition in APP/PS1 mice.

Immune dysfunction is implicated in Alzheimer's disease (AD), whereas systemic immune modulation may be neuroprotective. Our previous results have indicated immune challenge with Bacillus Calmette-Guerin attenuates AD pathology in animal models by boosting the systemic immune system. Similarly, independent studies have shown that boosting systemic immune system, by blocking PD-1 checkpoint pathway, modifies AD.

Intraperitoneal injection of IFN-γ restores microglial autophagy, promotes amyloid-β clearance and improves cognition in APP/PS1 mice.

Autophagy is a major self-degradative process that maintains cellular homeostasis and function in mammalian cells. Autophagic dysfunction occurs in the early pathogenesis of Alzheimer's disease (AD) and directly regulates amyloid-β (Aβ) metabolism. Although it has been proven that the cytokine IFN-γ enhances autophagy in macrophage cell lines, whether the signaling cascade is implicated in Aβ degradation in AD mouse models remains to be elucidated.

Influenza vaccination in early Alzheimer's disease rescues amyloidosis and ameliorates cognitive deficits in APP/PS1 mice by inhibiting regulatory T cells.

Background: Alzheimer's disease (AD) is a neurodegenerative disorder strongly correlated with a dysfunctional immune system. Our previous results demonstrated that inactivated influenza vaccine (IIV) facilitates hippocampal neurogenesis and blocks lipopolysaccharide (LPS)-induced cognitive impairment. However, whether IIV improves cognitive deficits in an AD mouse model remains unclear.

Prenatal influenza vaccination rescues impairments of social behavior and lamination in a mouse model of autism.

Background: Prenatal infection is a substantial risk factor for neurodevelopmental disorders such as autism in offspring. We have previously reported that influenza vaccination (VAC) during early pregnancy contributes to neurogenesis and behavioral function in offspring.

Results: Here, we probe the efficacy of VAC pretreatment on autism-like behaviors in a lipopolysaccharide (LPS)-induced maternal immune activation (MIA) mouse model.

IL-4 mediates the delayed neurobehavioral impairments induced by neonatal hepatitis B vaccination that involves the down-regulation of the IL-4 receptor in the hippocampus.

We have previously verified that neonatal hepatitis B vaccination induced hippocampal neuroinflammation and behavior impairments in mice. However, the exact mechanism of these effects remain unclear. In this study, we observed that neonatal hepatitis B vaccination induced an anti-inflammatory cytokine response lasting for 4-5 weeks in both the serum and the hippocampus, primarily indicated by elevated IL-4 levels.

Immunization with Bacillus Calmette-Guérin (BCG) alleviates neuroinflammation and cognitive deficits in APP/PS1 mice via the recruitment of inflammation-resolving monocytes to the brain.

The immune system plays a crucial role in the progression of Alzheimer's disease (AD). Recently, immune-dependent cascade induced by systemic immune activation has been verified to play a beneficial role in AD mouse models. Here, we tested whether Bacillus Calmette-Guérin (BCG) immunization alters AD pathology and cognitive dysfunction in APP/PS1 AD mouse model, and with 4Aβ1-15 vaccination as positive control.

Combined effect of BCG vaccination and enriched environment promote neurogenesis and spatial cognition via a shift in meningeal macrophage M2 polarization.

Background: The spatial learning abilities of developing mice benefit from extrinsic cues, such as an enriched environment, with concomitant enhancement in cognitive functions. Interestingly, such enhancements can be further increased through intrinsic Bacillus Calmette-Guérin (BCG) vaccination.

Results: Here, we first report that combined neonatal BCG vaccination and exposure to an enriched environment (Enr) induced combined neurobeneficial effects, including hippocampal long-term potentiation, and increased neurogenesis and spatial learning and memory, in mice exposed to the Enr and vaccinated with BCG relative to those in the Enr that did not receive BCG vaccination.

Continuous vaccinations of 4Aβ1-15 induces specific fluctuation of inflammatory factors accompany with pathologic alterations alleviation in APP/PS1 mice.

The common pathological hallmark of Alzheimer's disease (AD) is β-amyloid plaques deposition. Immunotherapy is a revolutionary pharmacological treatment for AD, aiming at improving plaque clearance while concomitantly decreasing inflammation. Our previous study prepared antigen 4Aβ1-15 and found that it could alleviate pathologic alterations in APP/PS1 transgenic mice.