Treadmill exercise improves neurological function by inhibiting autophagy and the binding of HMGB1 to Beclin1 in MCAO juvenile rats

Publication date: Available online 8 January 2020Source: Life SciencesAuthor(s): Guoyuan Pan, Lingqin Jin, Weimin Shen, Jieqiong Zhang, Juanjuan Pan, Jingyan Cheng, Qingfeng Xie, Quan Hu, Shamin Wu, Hongmei Zhang, Xiang ChenAbstractAimsTreadmill exercise is a beneficial treatment following childhood stroke. Thus, studies focusing on the neuroprotective mechanism of exercise training during postischemic treatment in children with ischemic stroke are urgently needed. We evaluated the effects of treadmill exercise on autophagy after cerebral ischemia in young rats.Main methodsRats (23–25 days old) underwent cerebral ischemia-reperfusion (CI/R) surgery. The experimental animals were divided into 5 groups, and some groups received either treadmill exercise, a rapamycin (RAPA) injection or combination therapy for 3 or 7 days. We performed a series of experimental tests including neurological scoring, hematoxylin-eosin staining (H&E), Nissl staining, triphenyl tetrazolium chloride (TTC) staining, Western blot analysis (WB), immunofluorescence (IF), enzyme-linked immunosorbent assay (ELISA), transmission electron microscopy (TEM) and Terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) fluorescence.Key findingsThe experimental data indicated that treadmill exercise inhibited autophagy in the ischemic penumbra, inhibited high mobility group box 1 (HMGB1) translocation and binding to Beclin1, reduced apoptosis, reduced infarct volumes, and...
Source: Life Sciences - Category: Biology Source Type: research

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Mammalian mitochondrial permeability transition pore (MPTP), across the inner and outer membranes of mitochondria, is a nonspecific channel for signal transduction or material transfer between mitochondrial matrix and cytoplasm such as maintenance of Ca2+ homeostasis, regulation of oxidative stress signals, and protein translocation evoked by some of stimuli. Continuous MPTP opening has been proved to stimulate neuronal apoptosis in ischemic stroke. Meanwhile, inhibition of MPTP overopening-induced apoptosis has shown excellent efficacy in the treatment of ischemic stroke. Among of which, the potential molecular mechanisms...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
ConclusionTGs are the main active components of C. deserticola against MCAO/R-induced cerebral injury, and protection is mainly via the Nrf-2/Keap-1 pathway.
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Abstract A series of 1,2,4-triazole derivatives 1-14 was synthesized to investigate their neuroprotective effects and mechanisms of action. Compounds 5-11 noticeably protected PC12 cells from the cytotoxicity of H2O2 or sodium nitroprusside (SNP). Compound 11 was the most effective derivative. Compound 11 chelated Fe (II) iron, scavenged reactive oxygen species (ROS), and restored the mitochondrial membrane potential (MMP). Moreover, it enhanced the activity of the antioxidant defense system by increasing the serum level of superoxide dismutase (SOD) and promoting the nuclear translocation of nuclear factor e...
Source: European Journal of Medicinal Chemistry - Category: Chemistry Authors: Tags: Eur J Med Chem Source Type: research
AbstractSpreading depolarization is observed as a large negative shift of the direct current potential, swelling of neuronal somas, and dendritic beading in the brain ’s gray matter and represents a state of a potentially reversible mass injury. Its hallmark is the abrupt, massive ion translocation between intraneuronal and extracellular compartment that causes water uptake (= cytotoxic edema) and massive glutamate release. Dependent on the tissue’s energy st atus, spreading depolarization can co-occur with different depression or silencing patterns of spontaneous activity. In adequately supplied tissue, spread...
Source: AGE - Category: Geriatrics Source Type: research
Publication date: Available online 6 December 2019Source: Chemico-Biological InteractionsAuthor(s): Chaosheng Zeng, Desheng Wang, Cong Chen, Lin Chen, Bocan Chen, Li Li, Min Chen, Huaijie XingAbstractStroke has been considered the second leading cause of death worldwide, and ischemic stroke accounts for the vast majority of stroke cases. Some of the main features of ischemic stroke are increased brain permeability, ischemia/reperfusion injury, oxidative stress, and acute inflammation. Antagonism of cysLT1R has been shown to provide cardiovascular and neural benefits. In the present study, we investigated the effects of the...
Source: Chemico Biological Interactions - Category: Biochemistry Source Type: research
Abstract Stroke has been considered the second leading cause of death worldwide, and ischemic stroke accounts for the vast majority of stroke cases. Some of the main features of ischemic stroke are increased brain permeability, ischemia/reperfusion injury, oxidative stress, and acute inflammation. Antagonism of cysLT1R has been shown to provide cardiovascular and neural benefits. In the present study, we investigated the effects of the cysLT1R antagonist zafirlukast both in vivo and in vitro using a middle cerebral artery occlusion (MCAO) mouse model and human brain microvascular endothelial cells (HBMVECs). In vi...
Source: Chemico-Biological Interactions - Category: Molecular Biology Authors: Tags: Chem Biol Interact Source Type: research
In conclusion, these results demonstrate that Ropinirole treatment is beneficial in preserving the mitochondrial functions that are altered in cerebral ischemic injury and thus can help in defining better therapies. PMID: 31816341 [PubMed - as supplied by publisher]
Source: Neurotoxicology - Category: Neurology Authors: Tags: Neurotoxicology Source Type: research
Abstract Cerebral ischemia-reperfusion injury is a complex pathophysiological process. Poly(ADP-ribose) (PAR) polymerase-1 (PARP-1)/apoptosis-inducing factor (AIF) signaling pathway-mediated apoptosis is one of the non-caspase-dependent cell death programs that are widely present in neurological diseases such as stroke. In our study, we aimed to conduct further research on the effects of Gualou Guizhi decoction (GLGZD) on the PARP-1/AIF signaling pathway in cell apoptosis after ischemia-reperfusion injury caused by middle cerebral artery occlusion (MCAO). The results showed that GLGZD administration for 7 day...
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research
CONCLUSIONS The results indicated that biochanin A protected the brain against ischemic injury in rats by anti-oxidative and anti-inflammatory actions. The activation of the Nrf2 pathway and the inhibition of the NF-kappaB pathway may contribute to the neuroprotective effects of biochanin A. PMID: 31767824 [PubMed - in process]
Source: Medical Science Monitor - Category: Research Tags: Med Sci Monit Source Type: research
In this study, we explored the role of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (Malat1) in the process of BBR-induced inhibition of HMGB1 in ischemic brain. Before the 60-min MCAO surgery, the mice were pretreated with BBR (50 mg· kg-1 per day, ig) for 14 days or ICV injected with specific lentiviral vector or shRNA. We showed that MCAO caused marked increase in the expression Malat1 and HMGB1 in the ipsilateral cortex, which was significantly attenuated by pretreatment with BBR. Knockdown of Malat1 attenuated the inflammatory injury after brain ischemia, whereas overexpression of...
Source: Acta Pharmacologica Sinica - Category: Drugs & Pharmacology Authors: Tags: Acta Pharmacol Sin Source Type: research
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