L-3-n-Butylphthalide (L-NBP) exerts neuroprotective effects in animal models of cerebral ischemia, but its potential benefits in repeated cerebral ischemia-reperfusion (RCIR) injury remain unknown. We investigated the effect of L-NBP on cognitive impairment induced by RCIR in mice. Male C57Bl/6 mice received sham surgery or bilateral common carotid artery occlusion (3 times, 20 min each) and were orally administered preoperative L-NBP (30 mg/kg/day, 7 days), postoperative L-NBP (30 or 60 mg/kg/day, 28 days) or postoperative vehicle (28 days). Learning and memory were assessed by the Morris water maze task and step-down passive avoidance test. Nissl staining was used to identify pathologic changes in the hippocampal CA1 region. The expressions of proteins associated with signaling, apoptosis and autophagy were assessed by quantitative PCR and western blot. RCIR induced deficits in learning and memory that were alleviated by preoperative or postoperative L-NBP administration. Pathologic lesions in the hippocampal CA1 region induced by RCIR were less severe in mice treated with L-NBP. Preoperative or postoperative L-NBP administration in mice receiving RCIR promoted hippocampal expression of phospho-Akt and phospho-mTOR (suggesting activation of Akt/mTOR signaling), increased the Bcl-2/Bax ratio (indicating suppression of apoptosis) and reduced the LC3-II/LC3-I ratio (implying inhibition of autophagy). Preoperative or postoperative L-NBP administration also depressed hippocampal levels of beclin-1 mRNA (indicating suppression of autophagy). These findings suggest that the effect of L-NBP to alleviate learning and memory deficits in mice following RCIR may involve activation of Akt/mTOR signaling and regulation of the expressions of proteins related to apoptosis and autophagy.

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Objective: The primary purpose of our study is to systemically evaluate the effect of repetitive transcranial magnetic stimulation (rTMS) on recovery of dysphagia after stroke.Search Methods: We searched randomized controlled trials (RCTs) and non-RCTs published by PubMed, the Cochrane Library, ScienceDirect, MEDLINE, and Web of Science from inception until April 24, 2021. Language is limited to English. After screening and extracting the data, and evaluating the quality of the selected literature, we carried out the meta-analysis with software RevMan 5.3 and summarized available evidence from non-RCTs.Results: Among 205 potentially relevant articles, 189 participants (from 10 RCTs) were recruited in the meta-analysis, and six non-RCTs were qualitatively described. The random-effects model analysis revealed a pooled effect size of SMD = 0.65 (95% CI = 0.04–1.26, p = 0.04), which indicated that rTMS therapy has a better effect than conventional therapy. However, the subgroup analysis showed that there was no significant difference between low-frequency and high-frequency groups. Even more surprisingly, there were no statistically significant differences between the two groups and the conventional training group in the subgroup analysis, but the combined effect was positive.Conclusion: Our study suggests that rTMS might be effective in treating patients with dysphagia after stroke.

This study's data support a role for eNOS in cognitive performance after stroke. This finding may lead to the development of novel interventions to treat poststroke cognitive deficits.