Ependymal/subventricular zone cells migrate to the peri-infarct region and differentiate into neurons and astrocytes after focal cerebral ischemia in adult rats

Abstract

Abstract: Objective To investigate the migration and differentiation of ependymal/ subventricular zone cells after focal cerebral ischemia in rats, and reveal the origin of the newly generated neural cells in the peri-infarct region. Methods Normal adult male Sprague Dawley rats weighing 250-350 g were used in this study. Before middle cerebral artery occlusion (MCAO), 10 μl of 0.2% DiI was injected into the lateral ventricle for prelabeling the ependymal/subventricular zone cells. After ischemia, cumulative BrdU labeling was employed to detect the newly generated cells and double immunofluorescent staining to identify cell differentiation. The labeled cells were observed with laser confocal microscopy. Results In the non-ischemic control rats, DiI-labeled cells resided in the ependyma/subventricular zone. After focal cerebral ischemia, DiI-labeled cells were found in the corpus callosum, adjacent striatum and cortex, and some DiI/BrdU/glial fibrillary acidic protein (GFAP)-positive cells or DiI/BrdU/ neuronal nuclear antigen (NeuN)-positive cells were observed in the peri-infarct region in the striatum or cortex since day 14 after MCAO. Conclusion After focal cerebral ischemia, ependymal/subventricular zone cells migrate into the peri-infarct region where they differentiate into neurons and astrocytes. This finding may be important for understanding the source of adult neural stem cells and for developing new therapeutic intervention strategy through enhancing endogenous neurogenesis after brain injury.

CLC Number:

ZHANG Peng-bo^1,2, LIU Yong¹, LI Jie¹, KANG Qian-yan¹, TIAN Ying-fang¹, CHEN Xin-lin¹, ZHAO Jian-jun¹, SHI Qin-dong¹, SONG Tu-sheng¹, QIAN Yi-hua¹. Ependymal/subventricular zone cells migrate to the peri-infarct region and differentiate into neurons and astrocytes after focal cerebral ischemia in adult rats[J]. Journal of Southern Medical University, 2005, 25(10): 1201-1206.

References

[1] Gould E, Gross CG. Neurogenesis in the adult mammals: some progress and problems[J].J Neurosci, 2002, 22(3): 619-23.
[2] Temple S. The development of neural stem cells [J]. Nature, 2001,414(6859): 112-7.
[3] Gould E, Tanapat P. Lesion-induced proliferation of neuronal progenitors in the dentate gyrus of the adult rat [J]. J Neurosci, 1997,80(2): 427-36.
[4] Liu J, Solway K, Messing RO, et al. Increased neurogenesis in the dentate gyrus after transient global ischemia in gerbils [J]. J Neurosci, 1998, 18(19): 7768-78.
[5] Magavi SS, Leavitt BR, Macklis JD. Induction of neurogenesis in the neocortex of adult mice[J]. Nature, 2000, 405(6789): 951-5.
[6] Yoshimura S, Takagi Y, Harada J, et al. FGF-2 regulation of neurogenesis in adult hippocampus after brain injury [J]. Proc Natl Acad Sci USA, 2001,98(10): 5874-9.
[7] Johansson CB, Momma S, Clarke DL, et al. Identification of a neural stem cells in the adult mammalian central nervous system [J]. Cell,1999, 96(1): 25-34.
[8] Yamamoto S, Nagao M, Sugimori M, et al. Transcription factor expression and Notch-dependent regulation of neural progenitors in the adult rat spinal cord[J]. J Neurosci, 2001,21(24): 9814-23.
[9] Yamamoto S, Yamamoto N, Kitamura T, et al. Proliferation of parenchymal neural progenitors in response to injury in the adult rat spinal cord[J]. Exp Neurol, 2001, 172(1): 115-27.
[10] Jin K, Minami M, Lan JQ, et al. Neurogenesis in dentate subgranular zone and rostral subventricular zone after focal cerebral ischemia in the rat [J]. Proc Natl Acad Sci USA, 2001, 98(8): 4710-5.
[11] Gu W, Brannstrom T, Wester P. Cortical neurogenesis in adult rats after reversible photothrombotic stroke [J]. J Cereb Blood Flow Metab,2000, 20(8): 1166-73.
[12] Jin K, Sun Y, Xie L, et al. Directed migration of neuronal precursors into the ischemic cerebral cortex and striatum [J]. Mol Cell Neurosci,2003, 24(1): 171-89.
[13] Jiang W, Gu W, Brannstrom T, et al. Cortical neurogenesis in adult rats after transient middle cerebral artery occlusion [J]. Stroke, 2001,32(5): 1201-7.
[14] Newcomb JK, Zhao X, Pike BR, et al. Temporal profile of apoptotic-like changes in neurons and astrocytes following controlled cortical impact injury in the rat [J]. Exp Neurol, 1999, 158 (1):76-88.
[15] Geddes JW, Pettigrew LC, Holtz ML, et al. Permanent focal and transient global cerebral ischemia increase glial and neuronal expression of heme oxygenase-1, but not heme oxygenase-2, protein in rat brain [J].Neurosci Lett, 1996, 210(3): 205-8.
[16] Zhang RL, Zhang ZG, Zhang L, et al. Proliferation and differentiation of progenitor cells in the cortex and the subventricular zone in the adult rat after focal cerebral ischemia [J]. Neurosci, 2001, 105(1): 33-41.
[17] Brazel CY, Romanko MJ, Rothstein RP, et al. Roles of the mammalian subventricular zone in brain development [J]. Prog Neurobiol,2003, 69(1): 49-69.
[18] Nakatomi H, Kuriu T, Okabe S, et al. Regeneration of hippocampal pyramidal neurons after ischemic brain injury by recruitment of endogenous neural progenitors [J]. Cell, 2002, 110(4): 429-41.
[19] Romanko M J, Rola R, Fike JR, et al. Roles of the mammalian subventricular zone in cell replacement after brain injury [J]. Prog Neurobiol, 2004, 74(2): 77-99.
[20] Sato K, Hayashi T, Sasaki C, et al. Temporal and spatial differences of PSA-NCAM expression between young-adult and aged rats in normal and ischemic brains[J]. Brain Res, 2001, 922(1): 135-9.
[21] Felling R J, Levison SW. Enhanced neurogenesis following stroke [J]. J Neurosci Res, 2003, 73(3): 277-83.
[22] Parent JM, Vexler ZS, Gong C, et al. Rat forebrain neurogenesis and striatal neuron replacement after focal stroke [J]. Ann Neurol, 2002,52(6): 802-13.
[23] Arvidsson A, Collin T, Kirik D, et al. Neuronal replacement from endogenous precursors in the adult brain after stroke [J]. Nat Med,2002, 8(9): 963-70.