J Korean Med Sci.  2015 Oct;30(10):1496-1502. 10.3346/jkms.2015.30.10.1496.

Effects of Repetitive Transcranial Magnetic Stimulation on Behavioral Recovery during Early Stage of Traumatic Brain Injury in Rats

• Yoon KJ
• Lee YT
• Chung PW
• Lee YK
• Kim DY
• Chun MH

• KMID: 2344185
• DOI: http://doi.org/10.3346/jkms.2015.30.10.1496

Abstract

Repetitive transcranial magnetic stimulation (rTMS) is a promising technique that modulates neural networks. However, there were few studies evaluating the effects of rTMS in traumatic brain injury (TBI). Herein, we assessed the effectiveness of rTMS on behavioral recovery and metabolic changes using brain magnetic resonance spectroscopy (MRS) in a rat model of TBI. We also evaluated the safety of rTMS by measuring brain swelling with brain magnetic resonance imaging (MRI). Twenty male Sprague-Dawley rats underwent lateral fluid percussion and were randomly assigned to the sham (n=10) or the rTMS (n=10) group. rTMS was applied on the fourth day after TBI and consisted of 10 daily sessions for 2 weeks with 10 Hz frequency (total pulses=3,000). Although the rTMS group showed an anti-apoptotic effect around the peri-lesional area, functional improvements were not significantly different between the two groups. Additionally, rTMS did not modulate brain metabolites in MRS, nor was there any change of brain lesion or edema after magnetic stimulation. These data suggest that rTMS did not have beneficial effects on motor recovery during early stages of TBI, although an anti-apoptosis was observed in the peri-lesional area.

Keyword

Transcranial Magnetic Stimulation; Brain Injury; Apoptosis; Recovery; Bcl-2; BAX; TBI; rTMS

MeSH Terms

Animals
Behavior, Animal/physiology
Brain/*pathology
Brain Injuries/*pathology/psychology/*therapy
Disease Models, Animal
Magnetic Resonance Imaging
Male
Motor Activity/physiology
Rats
Rats, Sprague-Dawley
Recovery of Function/*physiology
Transcranial Magnetic Stimulation/*methods
Treatment Outcome

Figure

• 

  Fig. 1 Schematic location of the 3-mm craniectomy, which was performed at 1.5 mm to the right of the midline bregma over the primary motor cortex (A). Stimulation method of rTMS (B). Rats underwent ten daily sessions for two weeks. Each daily session consisted of 15 trains of 2 sec at a rate of 10 Hz, 80% intensity of the RMT with a 1-sec inter-train interval (3,000 impulses total). B, bregma; rTMS, repetitive transcranial magnetic stimulation; RMT, resting motor threshold.

• 

  Fig. 2 Results of Rotarod (A) and beam balance tests (B). There are no significant differences between the two groups (sham, n=10 rats; rTMS, n=10 rats). D4, 4 days after injury; D18, 18 days after injury; D25, 25 days after injury.

• 

  Fig. 3 Results of metabolites with MRS. T2WI showed the location of MRS voxel (white squre, 3×3×3 µL) in the peri-lesional site (A). There are no significant differences in Cho/Cr (B) or NAA/Cr (C) ratios between the two groups (sham, n=10 rats; rTMS, n=10 rats). Cho, choline; Cr, creatine; NAA, N-acetyl-aspartate; D4, 4 days after injury; D18, 18 days after injury; D25, 25 days after injury.

• 

  Fig. 4 Results of brain swelling with MRI (A). There is no significant difference in lesion volume or brain edema between the two groups (B & C). rTMS, repetitive transcranial magnetic stimulation; D4, 4 days after injury; D18, 18 days after injury; D25, 25 days after injury.

• 

  Fig. 5 Results of immunohistochemical staining with Bcl-2 and BAX (A). A significantly more number of Bcl-2 stained cells and a lesser number of BAX stained cells in the rTMS group compared with the sham group around the peri-lesional area (B). sham, n=10 rats; rTMS, n=10 rats. *P<0.05, Student's t-test. Bcl-2, B-cell lymphoma 2; BAX, Bcl-2 associated X protein; rTMS, repetitive transcranial magnetic stimulation.

• 

  Fig. 6 Results of western blot showed Bcl-2 and BAX bands (A). A significant increase in Bcl-2 expression and a decrease in BAX expression is observed in the rTMS group compared with the sham group (B). sham, n=10 rats; rTMS, n=10 rats. *P < 0.05, Student's t-test. Bcl-2, B-cell lymphoma 2; BAX, Bcl-2 associated X protein; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; rTMS, repetitive transcranial magnetic stimulation.

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