Objective To observe the effects of neurotrophin 3 (NT3)-chitosan on motor function, and proliferation and differentiation of the neural stem cells (NSCs) in the injury area and subventricular zone (SVZ) in rats with motor cortex injury. Methods Sixty-five Wistar rats were divided into control group (n=7), injury group (n=29) and NT3-chitosan group (n=29). The motor cortex was aspirated and removed as cerebral injury model. NT3-chitosan was immediately implanted into the injured area after operation, and the control group received no intervention. Pellet reaching test was performed to detect the recovery of the forelimb function, HE staining was used to observe the lesion cavity size, and immunofluorescence staining was used to observe the proliferation and differentiation of NSCs 3 days, 7 days, 14 days, 1 month, 2 months and 3 months after operation. Results The grasp success rate was higher (F>6.00, P≤0.05), and the lesion cavity size was significantly smaller (F>629.5, P<0.001) in the NT3-chitosan group than in the injury group. In the NSCs differentiation experiment, the number of BrdU cells at all the time points was significantly higher in the NT3-chitosan group than in the injury group (F>171.43, P<0.001). In the NSCs proliferation experiment, the number of BrdU positive cells was still significantly higher in the NT3-chitosan group than in the control group and in the injury group (F>155.06, P<0.001), the number of Dcx positive cells was significantly higher in the NT3-chitosan group than in the injury group (F=62.367, P<0.001), and the number of BrdU/Dcx positive cells was significantly higher in the NT3-chitosan group than in the control group (F=33.527, P<0.001). Conclusion NT3-chitosan could activate NSCs in the SVZ, and promote endogenous neurogenesis and forelimb function recovery in rats after motor cortex injury.
YANG Fei-xiang
,
ZHANG Ai-feng
,
HAO Peng
,
SHANG Jun-kui
,
DUAN Hong-mei
,
YANG Zhao-yang
,
LI Xiao-guang
. Effect of Neurotrophin 3-chitosan on Endogenous Neurogenesis and Motor Function after Motor Cortex Injury in Rats[J]. Chinese Journal of Rehabilitation Theory and Practice, 2017
, 23(2)
: 155
-161
.
DOI: 10.3969/j.issn.1006-9771.2017.02.008
[1] Geddes-Klein DM, Schiffman KB, Meaney DF. Mechanisms and consequences of neuronal stretch injury in vitro differ with the model of trauma [J]. J Neurotrauma, 2006, 23(2): 193-204.
[2] Geddes-Klein DM, Serbest G, Mesfin MN, et al. Pharmacologically induced calcium oscillations protect neurons from increases in cytosolic calcium after trauma [J]. J Neurochem, 2006, 97(2): 462-474.
[3] Zhong C, Zhao X, Van KC, et al. NAAG peptidase inhibitor increases dialysate NAAG and reduces glutamate, aspartate and GABA levels in the dorsal hippocampus following fluid percussion injury in the rat [J]. J Neurochem, 2006, 97(4): 1015-1025.
[4] Wang X, Hu J, She Y, et al. Cortical PKC inhibition promotes axonal regeneration of the corticospinal tract and forelimb functional recovery after cervical dorsal spinal hemisection in adult rats [J]. Cereb Cortex, 2014, 24(11): 3069-3079.
[5] Alvarez-Buylla A, Garcia-Verdugo JM, Tramontin AD. A unified hypothesis on the lineage of neural stem cells [J]. Nat Rev Neurosci, 2001, 2(4): 287-293.
[6] Barnabe-Heider F, Goritz C, Sabelstrom H, et al. Origin of new glial cells in intact and injured adult spinal cord [J]. Cell Stem Cell, 2010, 7(4): 470-482.
[7] Gage FH. Mammalian neural stem cells [J]. Science, 2000, 287(5457): 1433-1438.
[8] Luo Y, Coskun V, Liang A, et al. Single-cell transcriptome analyses reveal signals to activate dormant neural stem cells [J]. Cell, 2015, 161(5): 1175-1186.
[9] Yang Z, Duan H, Mo L, et al. The effect of the dosage of NT-3/chitosan carriers on the proliferation and differentiation of neural stem cells [J]. Biomaterials, 2010, 31(18): 4846-4854.
[10] Li X, Yang Z, Zhang A. The effect of neurotrophin-3/chitosan carriers on the proliferation and differentiation of neural stem cells [J]. Biomaterials, 2009, 30(28): 4978-4985.
[11] Yang Z, Zhang A, Duan H, et al. NT3-chitosan elicits robust endogenous neurogenesis to enable functional recovery after spinal cord injury [J]. Proc Natl Acad Sci U S A, 2015, 112(43): 13354-13359.
[12] Duan H, Ge W, Zhang A, et al. Transcriptome analyses reveal molecular mechanisms underlying functional recovery after spinal cord injury [J]. Proc Natl Acad Sci U S A, 2015, 112(43): 13360-13365.
[13] Mo L, Yang Z, Zhang A, et al. The repair of the injured adult rat hippocampus with NT-3-chitosan carriers [J]. Biomaterials, 2010, 31(8): 2184-2192.
[14] Song HJ, Stevens CF, Gage FH. Neural stem cells from adult hippocampus develop essential properties of functional CNS neurons [J]. Nat Neurosci, 2002, 5(5): 438-445.
[15] 李晓光,孙毅,杨朝阳. NT3-壳聚糖支架诱导内源性神经发生修复脊髓损伤[J]. 前沿科学, 2016, 10(1): 4-10.
[16] 孙敏,张皑峰,杨朝阳,等. 神经营养因子3壳聚糖支架诱导成年大鼠脑损伤后海马神经网络的形成[J]. 中国康复理论与实践, 2014, 20(5): 428-433.
[17] Li Y, Wu D, Wu C, et al. Changes in neural stem cells in the subventricular zone in a rat model of communicating hydrocephalus [J]. Neurosci Lett, 2014, 578: 153-158.
[18] Liu Y, Tang G, Zhang Z, et al. Metformin promotes focal angiogenesis and neurogenesis in mice following middle cerebral artery occlusion [J]. Neurosci Lett, 2014, 579: 46-51.
[19] Li QQ, Qiao GQ, Ma J, et al. Cortical neurogenesis in adult rats after ischemic brain injury: most new neurons fail to mature [J]. Neural Regen Res, 2015, 10(2): 277-285.
[20] Yi X, Jin G, Zhang X, et al. Cortical endogenic neural regeneration of adult rat after traumatic brain injury [J]. PLoS One, 2013, 8(7): e70306.
[21] Moraga A, Pradillo JM, Garcia-Culebras A, et al. Aging increases microglial proliferation, delays cell migration, and decreases cortical neurogenesis after focal cerebral ischemia [J]. J Neuroinflammation, 2015, 12: 87.
