Functional and histologic changes after repeated transcranial direct current stimulation in rat stroke model

Abstract

Transcranial direct current stimulation (tDCS) is associated with enhancement or weakening of the NMDA receptor activity and change of the cortical blood flow. Therefore, repeated tDCS of the brain with cerebrovascular injury will induce the functional and histologic changes. Sixty-one Sprague-Dawley rats with cerebrovascular injury were used. Twenty rats died during the experimental course. The 41 rats that survived were allocated to the exercise group, the anodal stimulation group, the cathodal stimulation group, or the control group according to the initial motor function. Two-week treatment schedules started from 2 days postoperatively. Garcia, modified foot fault, and rota-rod performance scores were checked at 2, 9, and 16 days postoperatively. After the experiments, rats were sacrificed for the evaluation of histologic changes (changes of the white matter axon and infarct volume). The anodal stimulation and exercise groups showed improvement of Garcia's and modified foot fault scores at 16 days postoperatively. No significant change of the infarct volume happened after exercise and tDCS. Neuronal axons at the internal capsule of infarct hemispheres showed better preserved axons in the anodal stimulation group. From these results, repeated tDCS might have a neuroprotective effect on neuronal axons in rat stroke model.

Keywords: Cerebrovascular Trauma; Electrical Stimulation; Exercise; Neuroprotection; White Matter.

Fig. 1

Transcranial direct current stimulation in rat stroke model. We used a cup electrode for the active and a rubber electrode for the reference. To reduce the skin impedance, the cup electrode was fixed by a molded plastic cup and the rubber electrode by gauzes.

Fig. 2

Garcia's motor behavior scores between control, anodal stimulation, cathodal stimulation, and exercise groups at postoperative 2, 9, and 16 days (white, gray, and black bars). The values in the Y-axis represent the Garcia's scores (3-18). Asterisks represent P values less than 0.05.

Fig. 3

Rota-rod performance scores between control, anodal stimulation, cathodal stimulation, and exercise groups at postoperative 2, 9, and 16 days (white, gray, and black bars). The values in the Y-axis represent the rotational speed (rpm) when a rat fell off the rod or rotated with the rod without moving.

Fig. 4

Modified foot fault scores between control, anodal stimulation, cathodal stimulation, and exercise groups at postoperative 2, 9, and 16 days (white, gray, and black bars). The values in the Y-axis represent the number of the forelimb misplacements over 1 minute period when a rat traversed the grid. Asterisks represent P values less than 0.05.

Fig. 5

Representative photomicrographs from bilateral internal capsules showing neural axons staining with Bielschowsky's method in rat stroke model (original magnification ×40 and ×12.5). (A) and (B) represent infarct and intact hemispheres at the level of internal capsules. The arrows in figures A and B represent the left and right internal capsules. (C) is the dorsal side of a rat brain section. (D) is a graph to show the optical density ratios in all groups. Optical density ratios of the infarct hemisphere to the intact one are measured and compared between them. Infarct areas in the anodal stimulation group show less neuronal axon and stain intensity changes than those in the control group.