Repetitive transcranial magnetic stimulation (rTMS) has increasingly been studied over the past decade to determine whether it has a therapeutic benefit on focal cerebral ischemia. However, the underlying mechanism of rTMS in this process remains unclear. In the current study, we investigated the effects of rTMS on the proliferation of adult neural stem cells (NSCs) and explored microRNAs (miRNAs) that were affected by rTMS. Our data showed that 10 Hz rTMS significantly increased the proliferation of adult NSCs after focal cerebral ischemia in the subventricular zone (SVZ), and the expression of miR-25 was obviously up-regulated in the ischemic cortex after rTMS. p57, an identified miR-25 target gene that regulates factors linked to NSC proliferation, was also evaluated, and it exhibited down-regulation. To further verify the role of miR-25, rats were injected with a single dose of antagomir-25 and were subjected to focal cerebral ischemia followed by rTMS treatment. The results confirmed that miR-25 could be repressed specifically and could drive the up-regulation of its target gene (p57), which resulted in the inhibition of adult NSC proliferation in the SVZ after rTMS. Thus, our studies strongly indicated that 10 Hz rTMS can promote the proliferation of adult NSCs in the SVZ after focal cerebral ischemia by regulating the miR-25/p57 pathway.

Spinal cord injury (SCI) often results in spasticity. There is currently no effective therapy for spasticity. Here, we describe a method to efficiently differentiate human pluripotent stem cells from spinal GABA neurons. After transplantation into the injured rat spinal cord, the DREADD (designer receptors exclusively activated by designer drug)-expressing spinal progenitors differentiate into GABA neurons, mitigating spasticity-like response of the rat hindlimbs and locomotion deficits in 3 months. Administering clozapine-N-oxide, which activates the grafted GABA neurons, further alleviates spasticity-like response, suggesting an integration of grafted GABA neurons into the local neural circuit. These results highlight the therapeutic potential of the spinal GABA neurons for SCI.

Electroacupuncture (EA) has shown protective effects on cognitive decline. However, the underlying molecular mechanisms are ill‐understood. The present study was undertaken to determine whether the cognitive function was ameliorated in cerebral hypoperfusion rats following EA and to investigate the role of PKA/CREB pathway. We used a rat 2‐vessel occlusion (2VO) model and delivered EA at Baihui (GV20) and Dazhui (GV14) acupoints. Morris water maze (MWM) task, electrophysiological recording, Golgi silver stain, Nissl stain, Western blot, and real‐time PCR were employed. EA significantly (1) ameliorated the spatial learning and memory deficits, (2) alleviated long‐term potentiation (LTP) impairment and the reduction of dendritic spine density, (3) suppressed the decline of phospho‐CREB (pCREB) protein, brain‐derived neurotrophic factor (BDNF) protein, and microRNA132 (miR132), and (4) reduced the increase of p250GAP protein of 2VO rats. These changes were partially blocked by a selective protein kinase A (PKA) inhibitor, N‐[2‐(p‐bromocinnamylamino)ethyl]‐5‐isoquinoline‐sulfonamide (H89), suggesting that the PKA/CREB pathway is potentially involved in the effects of EA. Moreover, any significant damage to the pyramidal cell layer of CA1 subregion was absent. These results demonstrated that EA could ameliorate learning and memory deficits and alleviate hippocampal synaptic plasticity impairment of cerebral hypoperfusion rats, potentially mediated by PKA/CREB signaling pathway.

Objective: To investigate the effects of electroacupuncture (EA) on the activation of astrocytes (AST) in the periinfarct region after cerebral ischemia, as well as to evaluate potential behavioural improvement after EA treatment. Methods: Male Wistar rats were randomly divided into normal, model and EA groups. Rats in each group were further divided into 7, 14 and 28 days sub-groups. A model of middle cerebral artery occlusion was established, followed by 7, 14 or 28 days of EA on ‘Bai hui’ and ‘Da zhui’ acupoints. The number of GFAP-immunoreactive cells was determined and behavioural tests were performed. Results: Many more GFAP-immunoreactive cells were detected in the EA group on day 14 than on day 7 after ischemia and a slightly decreased number of immunoreactive cells were observed on day 28. The results of behavioural tests of animals in the EA group on the beam balance performance and prehensile traction performance were superior to that of animals in the model group. Conclusion: These findings indicate that EA has the potential to activate AST in the periinfarct region and to avoid excess reactive gliosis and also can facilitate the recovery of post-ischemic behavioural dysfunction.

In this review, we present evidence about the changes of the GABAergic system on the hippocampus under the ischemic environment, which may be an underlying mechanism to the ischemia-induced cognitive deficit. GABAergic system, in contrast to the glutamatergic system, is considered to play an inhibitory effect on the central nervous system over the past several decades. It has received widespread attention in the area of schizophrenia and epilepsy. The GABAergic system has a significant effect in promoting neural development and formation of local neural circuits of the brain, which is the structural basis of cognitive function. There have been a number of reviews describing changes in the GABAergic system in cerebral ischemia in recent years. However, no study has investigated the changes in the system in the hippocampus during cerebral ischemic injury, which results in cognitive impairment, particularly at the chronic ischemic stage and the late phase of ischemia. We present a review of the changes of the GABAergic system in the hippocampus under ischemia, including GABA interneurons, extracellular GABA neurotransmitter, and GABA receptors. Several studies are also listed correlating amelioration of cognitive impairment by regulating the GABAergic system in the hippocampus damaged under ischemia. Furthermore, exogenous cell transplantation, which improves cognition by modulating the GABAergic system, will also be described in this review to bring new insight and strategy on solving cognitive deficits caused by cerebral ischemia.