Multiple cell death is involved in ischemic brain injury. Necroptosis, a recently reported cell death, may be the most suitable cell death mechanism in a subpopulation of neurons under ischemic injury. It reported that a small molecule, necrostatin-1 (Nec-1), has a potent inhibitory effect on necroptotic cell death in vivo and in vitro. The aim of the current study was to investigate the role of Nec-1 on cognitive function in chronic ischemic stroke mice induced by bilateral common carotid artery stenosis (BCAS). Here, 12-week-old C57BL/6 mice received intragastric administration with Nec-1 or vehicle for two weeks after stroke, and then, the effect and possible mechanism were determined. We demonstrated that inhibition of necroptosis prevented cognitive impairment and reduced inflammatory response in the ischemic brain injury mouse model. These data suggested that inhibition of necroptosis provided a potential therapeutic option for cognitive rehabilitation in chronic ischemic stroke.

Working memory impairment is a common cognitive dysfunction after traumatic brain injury (TBI), which severely affects the quality of life of patients. Acetylcholine is a neurotransmitter which is closely related to cognitive functions. In addition, epigenetic modifications are also related to cognitive functions. A neurorehabilitation strategy, enriched environment (EE) intervention, has been widely used to improve cognitive impairment. However, studies of the mechanism of EE on cholinergic system and epigenetic modifications in mouse with TBI have not been reported yet. In this paper, a mouse model with traumatic frontal lobe injury was established, and the mechanism on EE for the mice with TBI was explored. It was found that EE could improve Y-maze performance of mice with TBI, the function of cholinergic system, and the imbalance of acetylation homeostasis in the prefrontal cortex of contralateral side of TBI. In addition, EE also could increase the level of CREB binding protein and histones H3 acetylation at ChAT gene promoter region in the prefrontal cortex of contralateral side of TBI. These indicate that EE has an important effect on the improvement of working memory impairment and the underlying mechanism may involve in histones H3 acetylation at ChAT gene promoter regions in the prefrontal cortex.

Ischemic stroke is the second leading cause of death worldwide. Ischemia-induced cognitive dysfunction may result in a poor quality of life. Synaptic plasticity plays a key role in cognition promotion. An enriched environment (EE), which can attenuate cognitive deficits in chronic cerebral hypoperfusion, has been shown to facilitate synaptic plasticity. However, the effect of EE on synaptic plasticity in bilateral cerebral hemispheres in stroke remains unclear. This study used a permanent middle cerebral artery occlusion mouse model, which was divided into standard housing and EE groups. The Morris water maze test was performed to detect the cognitive function. Electron microscopy was used to determine the synapse numbers. The expression of SYN and GAP-43 was then quantified by immunofluorescence staining and Western blot analysis. Compared with the standard housing, EE promoted the cognitive function recovery in the mice with stroke. Moreover, EE increased the synapse numbers and the expression of SYN and GAP-43 in both the ipsilateral and contralateral hemispheres (P < 0.05). A further correlation analysis revealed a positive correlation between the cognitive function outcomes and the relative expression of GAP-43 and SYN. Furthermore, the correlation of the expression of GAP-43 and SYN with cognitive function was higher in the contralateral brain than in the ipsilateral brain. In conclusion, an EE may promote cognitive function via bilateral synaptic remodeling after cerebral ischemia. Also, the contralateral brain may play an important role in the recovery of cognitive function.

Article: Theta-burst transcranial magnetic stimulation for dysphagia patients during recovery stage of stroke: a randomized controlled trial - European Journal of Physical and Rehabilitation Medicine 2023 Sep 22 - Minerva Medica - Journals

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.