Abstract
Cerebral ischemia is the most prevalent form of clinical stroke. Repetitive transcranial magnetic stimulation (rTMS) can modulate excitability of the cerebral cortex, and this effect is maintained after the stimulation is terminated. However, the underlying mechanisms of rTMS in cerebral ischemia remain unclear. Herein, we identified the effect of rTMS on cerebral ischemia. The in vitro model was established using primary cultured neurons under the condition of oxygen-glucose deprivation (OGD), followed by 1 Hz or 10 Hz rTMS treatment. The levels of CREB, PKA and CaMKIV were depleted in neurons to explore the underlying regulation mechanisms of TrkB by rTMS via CREB. Rat models with cerebral ischemia were established by middle cerebral artery occlusion (MCAO) and stimulated with 1 Hz or 10 Hz rTMS to investigate the effect of rTMS on neurobehavior, CREB expression, cAMP/PKA and Ca2+/CaMKIV pathways. rTMS was observed to promote the nerve recovery ability in rats with cerebral ischemia, which was accompanied by high expression of TrkB. Besides, in OGD-treated neurons, rTMS activated CREB by upregulating cAMP/PKA and Ca2+/CaMKIV pathways. Moreover, rTMS induced the activation of CREB to upregulate TrkB. In MACO rats, rTMS promoted CREB expression and the content of CREB, cAMP and PKA phosphorylation, increased the CaMKIV phosphorylation, and promoted the interaction between CREB and TrkB. Taken together, rTMS promoted CREB expression and up-regulated TrkB to improve the neurological function in rats with cerebral ischemia by activating cAMP/PKA and Ca2+/CaMKIV pathways, which could be of great significance for cerebral ischemia therapy. Funding Statement: The authors declare: None. Declaration of Interests: The authors declare: None. Ethics Approval Statement: The animal experiment was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Animal Ethics Committee of North China University of Science and Technology Affiliated Hospital.
Highlights
Cerebral ischemia is the most prevalent form of clinical stroke
The above results suggested that the rat model of permanent focal cerebral ischemia was successfully established, which was characterized by most obvious cortical changes
In order to evaluate whether Repetitive transcranial magnetic stimulation (rTMS) stimulation could improve the neurological function of middle cerebral artery occlusion (MCAO) rats, the neurobehavioral changes in rats were examined at days 1, 3, 7 and 14 after injury
Summary
Repetitive transcranial magnetic stimulation (rTMS) can modulate excitability of the cerebral cortex, and this effect is maintained after the stimulation is terminated. The underlying mechanisms of rTMS in cerebral ischemia remain unclear. Cerebral ischemia is the most common stroke inducer, which is characterized by reduced blood flow to brain tissues, causing insufficient transport of glucose, oxygen and other nutrients, and resulting in metabolic changes and possibly cell death [1]. Neurological deficits induced by cerebral ischemia reperfusion injury were frequently detected after the blood flow was restored in patients with cerebral stroke [4]. Repetitive transcranial magnetic stimulation (rTMS) as a therapeutic approach for functional recovery of subacute cerebral ischemia has been linked to an anti-apoptotic mechanism in the peri-ischemic area [6]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
