Ann Rehabil Med.  2015 Jun;39(3):416-424. 10.5535/arm.2015.39.3.416.

Effect of Epidural Electrical Stimulation and Repetitive Transcranial Magnetic Stimulation in Rats With Diffuse Traumatic Brain Injury

• Yoon YS
• Cho KH
• Kim ES
• Lee MS
• Lee KJ

• KMID: 2165645
• DOI: http://doi.org/10.5535/arm.2015.39.3.416

Abstract

OBJECTIVE
To evaluate the effects of epidural electrical stimulation (EES) and repetitive transcranial magnetic stimulation (rTMS) on motor recovery and brain activity in a rat model of diffuse traumatic brain injury (TBI) compared to the control group.
METHODS
Thirty rats weighing 270-285 g with diffuse TBI with 45 kg/cm2 using a weight-drop model were assigned to one of three groups: the EES group (ES) (anodal electrical stimulation at 50 Hz), the rTMS group (MS) (magnetic stimulation at 10 Hz, 3-second stimulation with 6-second intervals, 4,000 total stimulations per day), and the sham-treated control group (sham) (no stimulation). They were pre-trained to perform a single-pellet reaching task (SPRT) and a rotarod test (RRT) for 14 days. Diffuse TBI was then induced and an electrode was implanted over the dominant motor cortex. The changes in SPRT success rate, RRT performance time rate and the expression of c-Fos after two weeks of EES or rTMS were tracked.
RESULTS
SPRT improved significantly from day 8 to day 12 in the ES group and from day 4 to day 14 in the MS group (p<0.05) compared to the sham group. RRT improved significantly from day 6 to day 11 in ES and from day 4 to day 9 in MS compared to the sham group. The ES and MS groups showed increased expression of c-Fos in the cerebral cortex compared to the sham group.
CONCLUSION
ES or MS in a rat model of diffuse TBI can be used to enhance motor recovery and brain activity.

Keyword

Electric stimulation; Transcranial magnetic stimulation; Brain injuries

MeSH Terms

Animals
Brain
Brain Injuries*
Cerebral Cortex
Electric Stimulation*
Electrodes
Models, Animal
Motor Cortex
Rats*
Rotarod Performance Test
Transcranial Magnetic Stimulation*

Figure

• 

  Fig. 1 Application of continuous epidural electrical stimulation (A) and repetitive transcranial magnetic stimulation (B) in the traumatic brain injured rat model.

• 

  Fig. 2 The success rates of the single-pellet reaching task (SPRT) in the ES, MS, and sham groups. The success rate of the ES group was significantly higher between day 8 and day 12 while that of the MS group was significantly higher from day 4 to day 14. Note that the success rate of SPRT in the MS group increased significantly compared to the other two groups between day 4 and day 5. a)p<0.05 by one-way analysis of variance (ANOVA) with post-hoc comparison between the ES and sham groups, b)p<0.05 by one-way ANOVA with post-hoc comparison between the MS and sham groups. ES, electrical stimulation; MS, magnetic stimulation; Op, operation; POD, postoperative day.

• 

  Fig. 3 The average time for the rotarod test (RRT) in the ES, MS, and sham groups. The average time for RRT in the ES group was significantly longer than in the sham group from day 6 to day 11, while that of the MS group was significantly longer than that of the sham group from day 4 to day 9. The MS group showed a more significant increase in average RRT time compared to the other two groups on day 4, whereas the ES group showed a more significant increase than the other two groups between day 8 and day 10. a)p<0.05 by one-way analysis of variance (ANOVA) with post-hoc comparison between the ES and sham group, b)p<0.05 by one-way ANOVA with post-hoc comparison between the MS and sham group. ES, electrical stimulation; MS, magnetic stimulation; Op, operation; POD, postoperative day.

• 

  Fig. 4 Hematoxylin-eosin staining shows the injured area in the left and right hemispheres. In (A), focal hemorrhage (arrows) in the cerebral cortex, deep white matter, base, and necrosis with hygroma (void arrow) can be observed because of diffuse cerebral contusion. (B) shows lots of dead cells that have no nucleus throughout the brain parenchyme in the left (a, ×100) and the right (b, ×100) sides. Red circles indicate the nuclear vacuolation in the brain cell after traumatic brain injury in the dominant (c, ×400) and the non-dominant (d, ×400) sides of the cerebral hemisphere.

• 

  Fig. 5 Immunohistochemistry staining for c-Fos protein in the cerebral cortex of rats with diffuse traumatic brain injuries. The left (stimulation) and the right (non-stimulation) cortex in the ES group (A). The dominant and non-dominant cerebral cortex in the MS group (B) and in the sham group (C). In (A), note the increase in c-Fos expression on both sides, although the increase is more pronounced on the stimulated side, In (B), note the increase in c-Fos expression over the entire cerebral cortex, with the same level of expression on both sides. In (C), there is c-Fos expression on both sides, with much lower expression than in the ES group (A) and the MS group (B). ES, electrical stimulation; MS, magnetic stimulation.

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