ABSTRACT
Electroacupuncture (EA) treatment plays a protective role in cerebral ischemiareperfusion (CIR) injury. However, the underlying molecular mechanism is still not fully elucidated. METHODS: All rats were randomly divided into five groups: the SHAM group, MCAO group, MCAO+EA (MEA) group, MCAO+METTL3 overexpression+EA (METTL3) group and MCAO+lncRNA H19 overexpression+EA (lncRNA H19) group. The middle cerebral artery occlusion (MCAO) rats were established to mimic CIR injury. The overexpression of lncRNA H19 and METTL3 was induced by stereotactic injection of lentiviruses into the rat lateral ventricles. The rats in the MEA, METTL3, and lncRNA H19 groups were treated with EA therapy on "Renzhong" (DU26) and "Baihui" (DU20) acupoints (3.85/6.25Hz; 1mA). Besides, the neurological deficit scoring, cerebral infarction area, pathological changes in brain tissue, total RNA m6A level, and the expression of METTL3, S1PR2, TLR4, NLRP3 and lncRNA H19 were detected in this experiment. RESULTS: EA improved the neurological deficit scoring, cerebral infarction area, and pathological injury in MCAO rats, while these beneficial effects of EA on CIR injury were attenuated by the overexpression of METTL3 or lncRNA H19. More importantly, EA down-regulated the total RNA m6A level and the expression of METTL3, S1PR2, TLR4, NLRP3 and lncRNA H19 in MCAO rats. Instead, the overexpression of METTL3 or lncRNA H19 was found to reverse the EA-induced down-regulation. CONCLUSION: The findings indicated that EA might down-regulate the S1PR2/TLR4/NLRP3 signaling pathway via m6A methylation of lncRNA H19 to alleviate CIR injury. Our findings provide a new insight into the molecular mechanism of EA on CIR injury.
Subject(s)
Electroacupuncture , NLR Family, Pyrin Domain-Containing 3 Protein , RNA, Long Noncoding , Rats, Sprague-Dawley , Reperfusion Injury , Signal Transduction , Toll-Like Receptor 4 , Animals , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Electroacupuncture/methods , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Toll-Like Receptor 4/metabolism , Toll-Like Receptor 4/genetics , Reperfusion Injury/metabolism , Reperfusion Injury/therapy , Rats , Signal Transduction/physiology , Male , Infarction, Middle Cerebral Artery/therapy , Infarction, Middle Cerebral Artery/metabolism , Brain Ischemia/metabolism , Brain Ischemia/therapy , MethylationABSTRACT
BACKGROUND: Apathy is a frequent neuropsychiatric disorder in stroke patients. However, its prevalence rates have conflicting results across studies. This meta-analysis aimed to estimate the overall prevalence of apathy in stroke patients from 1990 to 2022. METHODS: PubMed, Web of Science, Embase and PsycINFO were systematically searched to identify relevant articles published from January 1, 1990 to October 29, 2022. Literature quality was assessed with the National Institutes of Health Study Quality Assessment Tool. The pooled prevalence, subgroup analyses and meta-regression were calculated by STATA 16.0. RESULTS: A total of 39 observational studies involving 5168 stroke patients were eligible for this meta-analysis. The pooled prevalence of apathy in stroke patients was 33.0% (95% CI, 27.6-38.4). Subgroup analyses showed that the pooled prevalence of apathy among stroke patients was higher in Japan (36.6%), China (33.7%) and Turkey (63.5%) compared to that in other countries (30.2%). The pooled prevalence of apathy was higher in ischemic stroke samples (36.1%) than in hemorrhagic stroke samples (14.4%). The pooled prevalence of apathy measured with the Apathy Evaluation Scale (38.3%) was the highest in stroke patients. Meta-regression presented that higher literature quality was significantly associated with lower prevalence, while stroke severity, mean age and female percentage were not significantly associated with the prevalence of apathy in stroke patients. CONCLUSION: Our findings revealed that the overall prevalence of apathy in stroke patients was 33.0% based on the current evidence. Furthermore, the prevalence was significantly correlated with countries, stroke subtypes, apathy criteria, and literature quality.
