High-frequency repetitive transcranial magnetic stimulation for treating moderate traumatic brain injury in rats: A pilot study

Abstract

Transcranial magnetic stimulation (TMS) is a method of noninvasive brain stimulation that causes neuromodulation by activating neurons or changing excitability in a certain brain area. Considering the known effects of TMS and the pathophysiology of traumatic brain injury (TBI), TMS was proposed to have potential for treating this condition. Moderate TBI was induced in adult male Sprague Dawley rats using Feeney's weight-dropping method. Injured rats were divided into a TMS group and a control group. Repetitive TMS (rTMS) was administered to rats in the TMS group from post-TBI day 2. At post-TBI days 7, 14 and 28, three or four of the rats were sacrificed, and harvested brains were embedded in paraffin and sectioned. Sections were then treated with hematoxylin and eosin and immunohistochemical staining. Three rats from each group underwent fludeoxyglucose F 18 micro-positron emission tomography scanning on post-TBI day 2 and 13. The unexpected mortality rate after injury was lower in the TMS group than in the control group. The modified neurological severity score of the TMS group was lower compared with the control group at post-TBI day 14. According to the results of hematoxylin eosin staining, relative cerebral parenchyma loss was lower at post-TBI day 28 in the TMS group compared with the control group. However, the aforementioned differences were not found to be statistically significant. There was also no significant difference in glucose metabolism between the two groups. According to immunohistochemical staining, the TMS group showed a significantly higher level of proliferation (indicated by bromodeoxyuridine) in the subventricular zone, as compared with the control group (P<0.05). A significantly higher rate of neuron survival at day 28 (P<0.05; indicated by NeuN) and a significantly reduced rate of apoptosis at days 7 and 14 (P<0.05; indicated by caspase-3) were observed in the perilesional zone of the TMS group, as compared with the control group. The current findings suggest that high-frequency rTMS may promote neurogenesis and provide a basis for further studies in this area.