DOI QR코드

DOI QR Code

Effect of Improved Forelimb Sensorimotor Function on the Transcranial Direct Current Stimulation in a Focal Ischemic Brain Injury Rat Model

국소 허혈성 뇌손상 흰쥐 모델에서 경두개직류전기자극이 앞다리 운동감각 기능 증진에 미치는 효과

  • 김기도 (한국국제대학교 물리치료학과) ;
  • 심기철 (동신대학교 보건복지대학 물리치료학과) ;
  • 김경윤 (동신대학교 보건복지대학 물리치료학과)
  • Received : 2010.10.04
  • Accepted : 2011.03.15
  • Published : 2011.04.28

Abstract

This study was to investigate the effect of improve forelimb sensorimotor function and neurotrophic factor(GAP-43) expression when differing an application time of tDCS in ischemic brain injury rat model(pre, $1^{st}$, $7^{th}$, $14^{th}$). Focal ischemic brain injury was induced in 80 Sprague-Dawley rats through middle cerebral artery occlusion(MCAO) by 'Longa' method. And then experimental groups were randomly divided into four groups; GroupI: MCAO induction, GroupII: application of tDCS(10 min) after MCAO induction, GroupIII: application of tDCS(20 min) after MCAO induction, GroupIV: application of tDCS(30 min) after MCAO induction. Modified limb placing test and single pellet reaching test were performed to test forelimb sensorimotor function. And the histological examination was also observed through the immunohistochemistric response of GAP-43(growth-associated protein-43) in the cerebral cortex. In modified limb placing test, groupIII(p<0.05) showed significantly improve than the other groups on $14^{th}$). day. In single pellet reaching test, groupIII(p<0.01) and groupIV(p<0.05) significantly improved on $14^{th}$) day. And in immunohistochemistric response of GAP-43, group III showed significantly positive response than the other groups on $14^{th}$ day. These results suggest that the intensity(0.1 mA)/time(20 min) condition of tDCS application has a significant impact on the sensorimotor functional recovery in focal ischemic brain injury rat models.

본 연구는 국소 허혈성 뇌손상 흰쥐 모델에서 tDCS의 자극 적용시간을 달리하였을 때, 앞다리 운동감각 기능변화와 신경영양인자(GAP-43)발현에 미치는 영향을 알아보고자 하였다. 뇌손상 모델은 Sprague -Dawley계 흰쥐 80마리를 'Longa'방법을 이용하여 중대뇌동맥(middle cerebral artery)을 폐색하여 유발하였고, 실험군을 4개로 나누었다; 실험군I은 허혈성 뇌손상 유발군(n=20), 실험군II는 허혈성 뇌손상 유발 후 tDCS(10분) 적용군(n=20), 실험군III은 허혈성 뇌손상 유발 후 tDCS(20분) 적용군(n=20), 실험군IV는 허혈성 뇌손상 유발 후 tDCS(30분) 적용군(n=20)으로 나누었다. 앞다리운동감각 기능검사를 위해 수정된 앞다리배치 검사와 단일 팰릿 닿기 검사를 실시하였으며, 신경가소성에 대한 면역조직화학적 검사로 운동감각 영역에서의 GAP-43 단백질 발현을 관찰하였다. 앞다리운동감각 검사는 14일에서 실험군III (p<0.05)이 다른 군들에 비해 유의한 차이를 보였으며, 단일 팰릿 닿기 검사는 14일에서 실험군III(p<0.01)과 실험군IV(p<0.05)에서 유의한 차이를 보였다. 또한, 면역조직학적 검사는 14일에 실험군III이 다른 군들에 비해 현저한 면역양성반응의 증가를 보였다. 따라서, 0.1 mA의 강도로 20분간 적용했을 때가 앞다리운동감각 기능과 신경가역성 인자 GAP-43 발현에 가장 좋은 조건임을 알 수 있었다.

Keywords

References

  1. A. Priori, A. Berardelli, S. Rona, N. Accornero, and M. Manfredi, "Polarization of the human motor cortex through the scalp," Neuroreport, Vol.13, No.9, pp.2257-2260, 1988.
  2. M. A. Nitsche and W. Paulus, "Excitability changes induced in human motor cortex by weak transcranial direct current stimulation," J Physiol, Vol.527, No.3, pp.633-639, 2000. https://doi.org/10.1111/j.1469-7793.2000.t01-1-00633.x
  3. C. Fraser, M. Power, S. Hamdy, J. Rothwell, D. Hobday, I. Hollander, P. Tyrell, A. Hobson, S. Williams, and D. Thompson, "Driving plasticity in human adult motor cortex is associated with improved motor function after brain injury," Neuron, Vol.34, No.5, pp.831-840, 2002. https://doi.org/10.1016/S0896-6273(02)00705-5
  4. B. R. Webster, P. A. Celnik, and L. G. Cohen, "Noninvasive brain stimulation in stroke rehabilitaton," NeuroRx, Vol.3, No.4, pp.474-481, 2006. https://doi.org/10.1016/j.nurx.2006.07.008
  5. C. Poreisz, K. Boros, A. Antal, and W. Paulus, "Safety aspects of transcranial direct current stimulation concerning healthy subjects and patients," Brain Res Bull, Vol.72, No.4-6, pp.208-214, 2007. https://doi.org/10.1016/j.brainresbull.2007.01.004
  6. D. Liebetanz, M. A. Nitsche, F. Tergau, and W. Paulus, "Pharmacological approach to the mechanisms of transcranial DC-stimulation-induced after-effects of human motor cortex excitability," Brain, Vol.125, No.10, pp.2238-2247, 2002. https://doi.org/10.1093/brain/awf238
  7. M. A. Nitsche, S. Doemkes, T. Karakose, A. Antal, D. Liebetanz, N. Lang, F. Tergau, and W. Paulus, "Shaping the effects of transcranial direct current stimulation of the human motor cortex," J Neurophysiol, Vol.97, No.4, pp.3109-3117, 2007. https://doi.org/10.1152/jn.01312.2006
  8. A. Prior, "Brain polarization in humans: a reappraisal of an old tool for prolonged non-invasive modulation of brain excitability," Clin Neurophysio, Vol.114, No.4, pp.589-595, 2003. https://doi.org/10.1016/S1388-2457(02)00437-6
  9. R. J. Nudo, E. J. Plautz, and S. B. Frost, "Role of adaptive plasticity in recovery of function after damage to motor cortex," Muscle Nerve, Vol.24, No.8, pp.1000-1019, 2001. https://doi.org/10.1002/mus.1104
  10. D. L. Adkins-Muir and T. A. Jones, "Cortical electrical stimulation combined with rehabilitative training: enhanced functional recovery and dendritic plasticity following focal cortical ischemia in rats," Neurol Res, Vol.25, No.8, pp.780-788, 2003. https://doi.org/10.1179/016164103771953853
  11. J. A. Kleim, R. Bruneau, P. VandenBerg, E. MacDonald, R. Mulrooney, and D. Pocock, "Motor cortex stimulation enhances motor recovery and reduces peri-infarct dysfunction following ischemic insult," Neurol Res, Vol.25, No.8, pp.789-793, 2003. https://doi.org/10.1179/016164103771953862
  12. A. K. McAllister, L. C. Katz, and D. C. Lo, "Neurotrophins and synaptic plasticity," Annu Rev Neurosci, Vol.22, pp.295-318, 1999. https://doi.org/10.1146/annurev.neuro.22.1.295
  13. L. I. Benowitz and A. Routtenberg, "An intrinsic determinant of neuronal development and plasticity," Trends Neurosci, Vol.20, No.2, pp.84-91, 1997. https://doi.org/10.1016/S0166-2236(96)10072-2
  14. D. Liebetanz, F. Klinker, D. Hering, R. Koch, M.A. Nitsche, H. Potschka, W. Loscher, W. Paulus, and F. Tergau, "Anticonvulsant effect of transcranial direct-current stimulation(tDCS) in the rat cortical ramp model of focal epilepsy," Epilepsia, Vol.47, No.7, pp.1216-1224, 2006. https://doi.org/10.1111/j.1528-1167.2006.00539.x
  15. D. Liebetanz, R. Koch, S. Mayenfels, F. Konig, W. Paulus, and M. A. Nitsche, "Safety limits of cathodal transcranial direct current stimulation in rats," Clin Neurophy, Vol.120, No.6, pp.1161-1167, 2009. https://doi.org/10.1016/j.clinph.2009.01.022
  16. J. B. Bederson, L. H. Pitts, M. Tsuji, M. C. Nishimura, R. L. Davis, and H. Bartkowski, "Rat middle cerebral atery occlusion: evaluation of the model and development of a neurologic examination," Stroke, Vol.17, No.3, pp.472-476, 1986. https://doi.org/10.1161/01.STR.17.3.472
  17. E. Z. Longa, P. R. Weinstein, S. Carlson, and R. Cummins, "Reversible middle cerebral artery occlusion without craniectomy in rats," Stroke, Vol.20, No.1, pp.84-91, 1989. https://doi.org/10.1161/01.STR.20.1.84
  18. 김상준, 뇌졸중 백서에서 반복적 경두개 직류 전기 자극에 의한 운동 기능 회복 기전, 서울대학교대학원 박사학위논문, 2009.
  19. S. W. Jeong, K. Chu, K. H. Jung, S. U. Kim, M. Kim, and J. K. Roh, "Human neural stem cell transplantation promotes functional recovery in rats with experimental intracerebral hemorrhage," Stroke, Vol.34, No.9, pp.2258-2263, 2003. https://doi.org/10.1161/01.STR.0000083698.20199.1F
  20. I. Q. Whishaw, W. T. O'Connor, and S. B. Dunnett, "The contributions of motor cortex, nigrostriatal dopamine and caudate-putamen to skilled forelimb use in the rat," Brain, Vol.109, No.5, pp.805-843, 1986. https://doi.org/10.1093/brain/109.5.805
  21. G. Paxinos, and C. Watson, The rat brain in stereotaxic coordinates. San Diego, Academic Press Inc., pp.13-38, 2005.
  22. Y. H. Kwon, M. H. Ko, S. H. Ahn, Y. H. Kim, J. C. Song, C. H. Lee, M. C. Chang, and S. H. Jang, "Primary motor cortex activation by transcranial direct current stimulation in the human brain," Neurosci Lett, Vol.435, No.1, pp.56-59, 2008. https://doi.org/10.1016/j.neulet.2008.02.012
  23. P. S. Boggio, L. O. Castro, E. A. Savagim, R. Braite, V. C. Cruz, R. R. Rocha, S. P. Rigonatti, M. T. Silva, and F. Fregni, "Enhancement of non-dominant hand motor function by anodal transcranial direct current stimulation," Neurosci Lett, Vol.404, No.1-2, pp.232-236, 2006. https://doi.org/10.1016/j.neulet.2006.05.051
  24. F. Hummel, P. Celnik, P. Giraux, A. Floel, W. H. Wu, C. Gerloff, and L. G. Cohen, "Effects of non-invasive cortical stimulation on skilled motor function in chronic stroke," Brain, Vol.128, No.3, pp.490-499, 2005. https://doi.org/10.1093/brain/awh369
  25. N. Lang, H. R. Siebner, N. S. Ward, L. Lee, M. A. Nitsche, W. Paulus, J. C. Rothwell, R. N. Lemon, and R. S. Frackowiak, "How does transcranial DC stimulation of the primary motor cortex alter regional neuronal activity in the human brain?," Eur J Neurosci, Vol.22, No.2, pp.495-504, 2005. https://doi.org/10.1111/j.1460-9568.2005.04233.x
  26. 고명환, E. M. Wassermann, 서정환, 김연희, 피질기저핵변성 환자에서 경두개 직류전류 자극 후 실행증 및 손기능 호전, 대한재활의학회지, Vol.31, No.3, pp.278-282, 2007.
  27. T. M. Barth, T. A. Jones, and T. Schallert, "Functional subdivisions of the rat somatic sensorimotor cortex," Behav Brain Res, Vol.39, No.1, pp.73-95, 1990. https://doi.org/10.1016/0166-4328(90)90122-U