Although skeletal muscle is the main effector organ largely accounting for disability after stroke, considerably less attention is paid to the secondary abnormalities of stroke‐related skeletal muscle loss. It is necessary to explore the mechanism of muscle atrophy after stroke and further develop effective rehabilitation strategy. Here, we evaluated the effects of high‐intensity interval (HIIT) versus moderate‐intensity aerobic training (MOD) on physical function, muscle mass, and stroke‐related gene expression profile of skeletal muscle. After the model of middle cerebral artery occlusion (MCAO) was successfully made, the blood lactate threshold corresponding speed (S_LT) and maximum speed (S_max) were measured. Different intensity training protocols (MOD < S_LT; S_LT < HIIT < S_max) were carried out for 3 weeks beginning at 7 days after MCAO in the MOD and HIIT groups, respectively. We found that both HIIT and MOD prevented stroke‐related gastrocnemius muscle mass loss in MCAO mice. HIIT was more beneficial than MOD for improvements in muscle strength, motor coordination, walking competency, and cardiorespiratory fitness. Furthermore, HIIT was superior to MOD in terms of reducing lipid accumulation, levels of IL‐1β and IL‐6 in paretic gastrocnemius, and improving peripheral blood CD4+/CD8+ T cell ratio, level of IL‐10. Additionally, RNA‐seq analysis revealed that the differentially expressed genes among HIIT, MOD, and MCAO groups were highly associated with signaling pathways involved in inflammatory response, more specifically the I‐kappaB kinase/NF‐kappaB signaling. Following the outcome, we further investigated the infiltrating immune cells abundant in paretic muscles. The results showed that HIIT modulated macrophage activation by downregulating CD86+ (M1 type) macrophages and upregulating CD163+ (M2 type) macrophages via inhibiting the TLR4/MyD88/NFκB signaling pathway and exerting an anti‐inflammatory effect in paretic skeletal muscle. It is expected that these data will provide novel insights into the mechanisms and potential targets underlying muscle wasting in stroke.

Fasudil, a Rho-associated protein kinase (ROCK) inhibitor, has a protective effect on the central nervous system. In addition, environmental enrichment is a promising technique for inducing the recovery of motor impairments in ischemic stroke models. The present study aimed to explore whether environmental enrichment combined with fasudil can facilitate motor function recovery and induce cortical axonal regeneration after stroke. First, a mouse model of ischemic cerebral stroke was established by photochemical embolization of the left sensorimotor cortex. Fasudil solution (10 mg/kg per day) was injected intraperitoneally for 21 days after the photothrombotic stroke. An environmental enrichment intervention was performed on days 7-21 after the photothrombotic stroke. The results revealed that environmental enrichment combined with fasudil improved motor function, increased growth-associated protein 43 expression in the infarcted cerebral cortex, promoted axonal regeneration on the contralateral side, and downregulated ROCK, p-LIM domain kinase (LIMK)1, and p-cofilin expression. The combined intervention was superior to monotherapy. These findings suggest that environmental enrichment combined with fasudil treatment promotes motor recovery after stroke, at least partly by stimulating axonal regeneration. The underlying mechanism might involve ROCK/LIMK1/cofilin pathway regulation. This study was approved by the Institutional Animal Care and Use Committee of Fudan University, China (approval No. 20160858A232) on February 24, 2016.

Objective: Recent studies have shown that irisin, a novel peptide hormone derived from muscles, could be used as a potential therapeutic drug against ischemic stroke. Moreover, electroacupuncture (EA) is widely used in the treatment of ischemic stroke. Yet, whether irisin is involved in the EA neuroprotection remains unclear. The following study investigated the association between serum and peri-lesional cortex irisin and EA-induced post-stroke motor recovery in rats. Methods: The middle cerebral artery occlusion (MCAO) method was used to induce ischemic stroke in rats. Rats were randomly divided into two groups: a middle cerebral artery occlusion (MCAO) group (MCAO rats without treatment) and an electroacupuncture (EA) group (MCAO rats treated with EA). On the 3rd day post-stroke, infarct volume, behavioral deficits, surviving neurons, irisin protein expression in peri-infarction cortex, muscle tissue, and serum were evaluated to identify the neuroprotective of EA in acute ischemic stroke. Results: Compared with the MCAO group, the EA group showed better behavioral performance, a smaller cerebral infarct volume, more surviving neurons, and a significant increase in irisin expression in the peri-infarction cortex and serum (p< 0.05). However, no difference in irisin expression in the muscle tissue was found between the MCAO group and the EA group (p> 0.05). Conclusion: EA promotes motor function recovery, reduces the volume of cerebral infarction, and alleviates neuronal death following ischemic stroke by enhancing the expression of irisin in both the blood and peri-lesional cortex.

Background: This study investigates the reliability of functional near-infrared spectroscopy (fNIRS) in detecting resting-state brain network characteristics in patients with mild cognitive impairment (MCI), focusing on static resting-state functional connectivity (sRSFC) and dynamic resting-state functional connectivity (dRSFC) patterns in MCI patients and healthy controls (HCs) without cognitive impairment. Methods: A total of 89 MCI patients and 83 HCs were characterized using neuropsychological scales. Subject sRSFC strength and dRSFC variability coefficients were evaluated via fNIRS. The study evaluated the feasibility of using fNIRS to measure these connectivity metrics and compared resting-state brain network characteristics between the two groups. Correlations with Montreal Cognitive Assessment (MoCA) scores were also explored. Results: sRSFC strength in homologous brain networks was significantly lower than in heterologous networks (p < 0.05). A significant negative correlation was also observed between sRSFC strength and dRSFC variability at both the group and individual levels (p < 0.001). While sRSFC strength did not differentiate between MCI patients and HCs, the dRSFC variability between the dorsal attention network (DAN) and default mode network (DMN), and between the ventral attention network (VAN) and visual network (VIS), emerged as sensitive biomarkers after false discovery rate correction (p < 0.05). No significant correlation was found between MoCA scores and connectivity measures. Conclusions: fNIRS can be used to study resting-state brain networks, with dRSFC variability being more sensitive than sRSFC strength for discriminating between MCI patients and HCs. The DAN-DMN and VAN-VIS regions were found to be particularly useful for the identification of dRSFC differences between the two groups. Clinical Trial Registration: ChiCTR2200057281, registered on 6 March, 2022; https://www.chictr.org.cn/showproj.html?proj=133808.

Background: Subcortical white matter lesions are exceedingly common in cerebral small vessel disease and lead to significant cumulative disability without an available treatment. Here, we tested a rho-kinase inhibitor on functional recovery after focal white matter injury. Methods: A focal corpus callosum lesion was induced by stereotactic injection of N ⁵ -(1-iminoethyl)-L-ornithine in mice. Fasudil (10 mg/kg) or vehicle was administered daily for 2 weeks, starting one day after lesion induction. Resting-state functional connectivity and grid walk performance were studied longitudinally, and lesion volumes were determined at one month. Results: Resting-state interhemispheric functional connectivity significantly recovered between days 1 and 14 in the fasudil group ( P <0.001), despite worse initial connectivity loss than vehicle before treatment onset. Grid walk test revealed an increased number of foot faults in the vehicle group compared with baseline, which persisted for at least 4 weeks. In contrast, the fasudil arm did not show an increase in foot faults and had smaller lesions at 4 weeks. Immunohistochemical examination of reactive astrocytosis, synaptic density, and mature oligodendrocytes did not reveal a significant difference between treatment arms. Conclusions: These data show that delayed fasudil posttreatment improves functional outcomes after a focal subcortical white matter lesion in mice. Future work will aim to elucidate the mechanisms.