Abstract
Exercise enhances neuronal stem cell (NSC) proliferation and neurogenesis. However, the effect of exercise on NSC proliferation surrounding the area of damage after traumatic brain injury (TBI) is unknown. Here, we investigate the effect of running on NSC proliferation following TBI in the rat. Wistar rats received TBI and were randomly divided into two groups: (1) non-exercise group and (2) exercise group. The exercise group ran on a treadmill for 30 min/day at 22 m/min for 7 consecutive days. Immunohistochemistry was used to monitor NSC proliferation around the damaged area, and ex vivo techniques were used to isolate NSCs from the damaged region in both groups. The number of nestin- and Ki67-positive cells observed at 3 and 7 days after TBI was significantly greater in the exercise group than in the non-exercise group (P < 0.01). Furthermore, most nestin-positive cells in the exercise group co-localized with Ki67-positive cells. In ex vivo studies, spheres could be isolated from injured brain tissue from the exercise group at 3 and 7 days following TBI, but at only 3 days in the non-exercise group. The number of spheres isolated from injured brain tissue was greater in the exercise group than in the non-exercise group. Spheres were immunopositive for nestin and comprised NSCs that could differentiate into neurons and glia. Exercise increases the proliferation of NSCs around the damaged area following TBI. Therefore, exercise therapy (rehabilitation) in the early phase following TBI is important for recuperation from cerebral dysfunction induced by TBI.
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Azbill RD, Mu X, Bruce-Keller AJ, Mattson MP, Springer JE (1997) Impaired mitochondrial function, oxidative stress and altered antioxidant enzyme activities following traumatic spinal cord injury. Brain Res 765:283–290
Blackmore DG, Golmohammadi MG, Large B, Waters MJ, Rietze RL (2009) Exercise increases neural stem cell number in a growth hormone-dependent manner, augmenting the regenerative response in aged mice. Stem Cells 27:2044–2052
Chen S, Pickard JD, Harris NG (2003) Time course of cellular pathology after controlled cortical impact injury. Exp Neurol 182:87–102
Chirumamilla S, Sun D, Bullock MR, Colello RJ (2002) Traumatic brain injury induced cell proliferation in the adult mammalian central nervous system. J Neurotrauma 19:693–703
Douen AG, Dong L, Vanance S, Munger R, Hogan MJ, Thompson CS, Hakim AM (2004) Regulation of nestin expression after cortical ablation in adult rat brain. Brain Res 1008:139–146
Gage FH (2000) Mammalian neural stem cells. Science 287:1433–1438
Itoh T, Satou T, Hashimoto S, Ito H (2005) Isolation of neural stem cells from damaged rat cerebral cortex after TBI. Neuroreport 16:1687–1691
Itoh T, Satou T, Nishida S, Hashimoto S, Ito H (2006) Cultured rat astrocytes give rise to neural stem cells. Neurochem Res 31:1381–1387
Itoh T, Satou T, Hashimoto S, Ito H (2007) Immature and mature neurons coexist among glial scars after rat traumatic brain injury. Neurol Res 29:734–742
Itoh T, Satou T, Ishida H, Nishida S, Tsubaki M, Hashimoto S, Ito H (2009a) The relationship between SDF-1alpha/CXCR4 and neural stem cells appearing in damaged area after traumatic brain injury in rats. Neurol Res 31:90–102
Itoh T, Satou T, Nishida S, Tsubaki M, Hashimoto S, Ito H (2009b) The novel free radical scavenger, edaravone, increases neural stem cell number around the area of damage following rat traumatic brain injury. Neurotox Res 16:378–389
Itoh T, Satou T, Nishida S, Tsubaki M, Imano M, Hashimoto S, Ito H (2010a) Edaravone protects against apoptotic neuronal cell death and improves cerebral function after traumatic brain injury in rats. Neurochem Res 35:348–355
Itoh T, Satou T, Takemori K, Hashimoto S, Ito H (2010b) Neural stem cells and new neurons in the cerebral cortex of stroke-prone spontaneously hypertensive rats after stroke. J Mol Neurosci 41:55–65
Kawamata T, Katayama Y, Hovda DA, Yoshino A, Becker DP (1995) Lactate accumulation following concussive brain injury: the role of ionic fluxes induced by excitatory amino acids. Brain Res 674:196–204
Komitova M, Zhao LR, Gido G, Johansson BB, Eriksson P (2005) Postischemic exercise attenuates whereas enriched environment has certain enhancing effects on lesion-induced subventricular zone activation in the adult rat. Eur J Neurosci 21:2397–2405
Kuhn HG, Dickinson-Anson H, Gage FH (1996) Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci 16:2027–2033
Leasure JL, Grider M (2010) The effect of mild post-stroke exercise on reactive neurogenesis and recovery of somatosensation in aged rats. Exp Neurol. doi:10.1016/j.expneurol.2010.08.003
Llorens-Martin M, Torres-Aleman I, Trejo JL (2010) Exercise modulates insulin-like growth factor 1-dependent and -independent effects on adult hippocampal neurogenesis and behaviour. Mol Cell Neurosci 44:109–117
Lois C, Alvarez-Buylla A (1994) Long-distance neuronal migration in the adult mammalian brain. Science 264:1145–1148
Luo CX, Jiang J, Zhou QG, Zhu XJ, Wang W, Zhang ZJ, Han X, Zhu DY (2007) Voluntary exercise-induced neurogenesis in the postischemic dentate gyrus is associated with spatial memory recovery from stroke. J Neurosci Res 85:1637–1646
McKay R (1997) Stem cells in the central nervous system. Science 276:66–71
Moon C, Ahn M, Kim S, Jin JK, Sim KB, Kim HM, Lee MY, Shin T (2004) Temporal patterns of the embryonic intermediate filaments nestin and vimentin expression in the cerebral cortex of adult rats after cryoinjury. Brain Res 1028:238–242
Parent JM, Yu TW, Leibowitz RT, Geschwind DH, Sloviter RS, Lowenstein DH (1997) Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. J Neurosci 17:3727–3738
Picard-Riera N, Nait-Oumesmar B, Baron-Van EA (2004) Endogenous adult neural stem cells: limits and potential to repair the injured central nervous system. J Neurosci Res 76:223–231
Radak Z, Kaneko T, Tahara S, Nakamoto H, Pucsok J, Sasvari M, Nyakas C, Goto S (2001) Regular exercise improves cognitive function and decreases oxidative damage in rat brain. Neurochem Int 38:17–23
Rice AC, Khaldi A, Harvey HB, Salman NJ, White F, Fillmore H, Bullock MR (2003) Proliferation and neuronal differentiation of mitotically active cells following traumatic brain injury. Exp Neurol 183:406–417
Seri B, Garcia-Verdugo JM, McEwen BS, Alvarez-Buylla A (2001) Astrocytes give rise to new neurons in the adult mammalian hippocampus. J Neurosci 21:7153–7160
Tani M, Hayakawa H, Yasuda T, Nihira T, Hattori N, Mizuno Y, Mochizuki H (2010) Ectopic expression of alpha-synuclein affects the migration of neural stem cells in mouse subventricular zone. J Neurochem. doi:10.1111/j.1471-4159.2010.06727.x
Uda M, Ishido M, Kami K, Masuhara M (2006) Effects of chronic treadmill running on neurogenesis in the dentate gyrus of the hippocampus of adult rat. Brain Res 1104:64–72
Wu CW, Chen YC, Yu L, Chen HI, Jen CJ, Huang AM, Tsai HJ, Chang YT, Kuo YM (2007) Treadmill exercise counteracts the suppressive effects of peripheral lipopolysaccharide on hippocampal neurogenesis and learning and memory. J Neurochem 103:2471–2481
Wu CW, Chang YT, Yu L, Chen HI, Jen CJ, Wu SY, Lo CP, Kuo YM (2008) Exercise enhances the proliferation of neural stem cells and neurite growth and survival of neuronal progenitor cells in dentate gyrus of middle-aged mice. J Appl Physiol 105:1585–1594
Xiong Y, Gu Q, Peterson PL, Muizelaar JP, Lee CP (1997) Mitochondrial dysfunction and calcium perturbation induced by traumatic brain injury. J Neurotrauma 14:23–34
Yagita Y, Kitagawa K, Sasaki T, Terasaki Y, Todo K, Omura-Matsuoka E, Matsumoto M, Hori M (2006) Postischemic exercise decreases neurogenesis in the adult rat dentate gyrus. Neurosci Lett 409:24–29
Yamamoto S, Nagao M, Sugimori M, Kosako H, Nakatomi H, Yamamoto N, Takebayashi H, Nabeshima Y, Kitamura T, Weinmaster G, Nakamura K, Nakafuku M (2001) Transcription factor expression and Notch-dependent regulation of neural progenitors in the adult rat spinal cord. J Neurosci 21:9814–9823
Yi SS, Hwang IK, Yoo KY, Park OK, Yu J, Yan B, Kim IY, Kim YN, Pai T, Song W, Lee IS, Won MH, Seong JK, Yoon YS (2009) Effects of treadmill exercise on cell proliferation and differentiation in the subgranular zone of the dentate gyrus in a rat model of type II diabetes. Neurochem Res 34:1039–1046
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This work was supported by a Grant-in-Aid for Scientific Research (20500472 and 21500803) and ZENRYOKEN. The authors thank Mari Yachi for technical assistance.
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Itoh, T., Imano, M., Nishida, S. et al. Exercise increases neural stem cell proliferation surrounding the area of damage following rat traumatic brain injury. J Neural Transm 118, 193–202 (2011). https://doi.org/10.1007/s00702-010-0495-3
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DOI: https://doi.org/10.1007/s00702-010-0495-3