Long-lasting regeneration after ischemia in the cerebral cortex

被引:207
作者
Leker, Ronen R.
Soldner, Frank
Velasco, Ivan
Gavin, Denise K.
Androutsellis-Theotokis, Andreas
McKay, Ronald D. G.
机构
[1] Hadassah Univ, Med Ctr, Dept Neurol, IL-91120 Jerusalem, Israel
[2] NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA
关键词
growth factors; neural progenitors; neural stem cells; neurogenesis; stroke;
D O I
10.1161/01.STR.0000252156.65953.a9
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background and Purpose-Because fibroblast growth factor 2 is a mitogen for central nervous system stern cells, we explored whether long-term fibroblast growth factor 2 delivery to the brain can improve functional outcome and induce cortical neurogenesis after ischemia. Methods-Rats underwent permanent distal middle cerebral artery occlusion resulting in an ischemic injury limited to the cortex. We used an adeno-associated virus transfection system to induce long-term fibroblast growth factor 2 expression and monitored behavioral and histological changes. Results-Treatment increased the number of proliferating cells and improved motor behavior. Neurogenesis continued throughout 90 days after the ischemia, and the occurrence of newly generated cells with characteristics of neural precursors and immature neurons was most evident 90 days after treatment. Conclusions-Focal cortical ischemia elicits an ongoing neurogenic response that can be enhanced with fibroblast growth factor 2 leading to improved functional outcome.
引用
收藏
页码:153 / 161
页数:9
相关论文
共 21 条
[1]
Neuronal replacement from endogenous precursors in the adult brain after stroke [J].
Arvidsson, A ;
Collin, T ;
Kirik, D ;
Kokaia, Z ;
Lindvall, O .
NATURE MEDICINE, 2002, 8 (09) :963-970
[2]
Doublecortin expression levels in adult brain reflect neurogenesis [J].
Couillard-Despres, S ;
Winner, B ;
Schaubeck, S ;
Aigner, R ;
Vroemen, M ;
Weidner, N ;
Bogdahn, U ;
Winkler, J ;
Kuhn, HG ;
Aigner, L .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2005, 21 (01) :1-14
[3]
Vascular changes in the subventricular zone after distal cortical lesions [J].
Gotts, JE ;
Chesselet, MF .
EXPERIMENTAL NEUROLOGY, 2005, 194 (01) :139-150
[4]
Migration and fate of newly born cells after focal cortical ischemia in adult rats [J].
Gotts, JE ;
Chesselet, MF .
JOURNAL OF NEUROSCIENCE RESEARCH, 2005, 80 (02) :160-171
[5]
HABERMAN R, 1999, CURRENT PROTOCOLS NE
[6]
Single factors direct the differentiation of stem cells from the fetal and adult central nervous system [J].
Johe, KK ;
Hazel, TG ;
Muller, T ;
DugichDjordjevic, MM ;
McKay, RDG .
GENES & DEVELOPMENT, 1996, 10 (24) :3129-3140
[7]
Adeno-associated virus effectively mediates conditional gene modification in the brain [J].
Kaspar, BK ;
Vissel, B ;
Bengoechea, T ;
Crone, S ;
Randolph-Moore, L ;
Muller, R ;
Brandon, EP ;
Schaffer, D ;
Verma, IM ;
Lee, KF ;
Heinemann, SF ;
Gage, FH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (04) :2320-2325
[8]
Enlarged infarct volume and loss of BDNF mRNA induction following brain ischemia in mice lacking FGF-2 [J].
Kiprianova, I ;
Schindowski, K ;
von Bohlen und Halbach, O ;
Krause, S ;
Dono, R ;
Schwaninger, M ;
Unsicker, K .
EXPERIMENTAL NEUROLOGY, 2004, 189 (02) :252-260
[9]
Enriched environment increases neural stem/progenitor cell proliferation and neurogenesis in the subventricular zone of stroke-lesioned adult rats [J].
Komitova, M ;
Mattsson, B ;
Johansson, BB ;
Eriksson, PS .
STROKE, 2005, 36 (06) :1278-1282
[10]
Sox-2 is expressed by neural progenitors and astroglia in the adult rat brain [J].
Komitova, M ;
Eriksson, PS .
NEUROSCIENCE LETTERS, 2004, 369 (01) :24-27