Neuroprotection of Low‐Frequency Repetitive Transcranial Magnetic Stimulation after Ischemic Stroke in Rats

Abstract

Objective: Stroke is a leading cause of human death and disability. Effective early treatments with reasonable therapeutic windows remain critically important to improve the outcomes of stroke. Transcranial magnetic stimulation (TMS) is an established noninvasive technique that has been applied clinically and in animal research for multiple brain disorders, but few studies have examined acute neuroprotection against ischemic stroke. The present investigation tested the novel approach of low-frequency repetitive TMS (rTMS) as an acute treatment after ischemic stroke. Methods: Adult male rats received focal ischemic surgery through occlusion of the right middle cerebral artery for 60 minutes. The rats received either rTMS or sham treatment with 1.5-, 3-, 4-, or 7-hour delay after the onset of stroke. Low-frequency and low-intensity rTMS was applied to the rat brain for two 30-minute episodes separated by a 1-hour interval.Results: Three days after stroke, compared to stroke controls, rats receiving rTMS treatment with a 1.5-hour delay showed a 35% reduction of infarct volume. Protective effects were also seen with 3-or 4-hour-delayed treatments by rTMS, shown as reduced infarct volume and cell death. rTMS treatment upregulated the antiapoptotic factor Bcl-2 and downregulated the proapoptotic caspase-3 cleavage, expressions of Bax and matrix metallopeptidase-9. In sensorimotor functional assessments 3 to 21 days after stroke, rats receiving rTMS treatment with a 1.5-or 3-hour delay showed significantly better performance compared to stroke controls. Interpretation: These results support the inference that low-frequency rTMS may be feasible as a neuroprotective acute treatment after ischemic stroke.

A translational roadmap for transcranial magnetic and direct current stimulation in stroke rehabilitation: Consensus-based core recommendations from the third stroke recovery and rehabilitation roundtable

“…Evidence-based translational barriers: (a) Preclinical response domains . Most preclinical studies (approximately 60%) focused on the use of tDCS or rTMS to promote neuroprotection and plasticity after stroke in relation to motor recovery, 40 with few studies testing functional recovery across multiple domains. These studies have provided crucial information about glial differentiation, neuronal gene regulation, and other molecular changes induced by NIBS.…”

Functional material-mediated wireless physical stimulation for neuro-modulation and regeneration

“…86 Another study by Buetefisch et al also suggested the neuroprotective effects of rTMS in stroke mice, as proven by the upregulated expression of anti-apoptotic proteins, reduction of pro-apoptotic molecules and decrease of cell death. 87 It has also been reported that magnetic stimulation is able to increase the plasticity of synapses and improve neurological dysfunction after injuries. Qian et al used rTMS as an efficient and painless brain stimulation approach to treat rats with traumatic brain injury (TBI).…”

A translational roadmap for transcranial magnetic and direct current stimulation in stroke rehabilitation: Consensus-based core recommendations from the third stroke recovery and rehabilitation roundtable

“…International Journal of Stroke, 19 (2) recovery, 40 with few studies testing functional recovery across multiple domains. These studies have provided crucial information about glial differentiation, neuronal gene regulation, and other molecular changes induced by NIBS.…”