Enhanced neurogenesis following stroke

Each year hundreds of thousands of people must cope with the severe neurological consequences of a stroke. Current therapeutic strategies for stroke focus on acute treatment and neuroprotection. Unfortunately, these practices do little to reduce the long‐term morbidity associated with the injury. To develop effective therapies that promote regeneration, we must have an understanding of the cellular and molecular events involved in the recovery from an insult. Neural stem and progenitor cells are likely to be affected during this period. Here we review how the proliferation, migration, and maturation of these precursors are affected by ischemia. Furthermore, we summarize data available on the underlying mechanisms and the therapeutic implications of these studies. The studies that we review provide compelling evidence that neural precursors resident in the brain initiate a compensatory response to stroke that results in the production of new neurons. Moreover, administration of growth factors can enhance this compensatory response. Based on these encouraging results, we may eventually be able to manipulate these precursors to improve recovery of function in individuals afflicted by this devastating injury. © 2003 Wiley‐Liss, Inc.

[1]  R. Galli,et al.  Emx2 regulates the proliferation of stem cells of the adult mammalian central nervous system. , 2002, Development.

[2]  U. Lendahl,et al.  Nestin mRNA expression correlates with the central nervous system progenitor cell state in many, but not all, regions of developing central nervous system. , 1995, Brain research. Developmental brain research.

[3]  K. Jin,et al.  Stem cell factor stimulates neurogenesis in vitro and in vivo. , 2002, The Journal of clinical investigation.

[4]  S. Higashiyama,et al.  Heparin-binding epidermal growth factor-like growth factor mRNA expression in neonatal rat brain with hypoxic/ischemic injury , 1999, Brain Research.

[5]  Kortaro Tanaka,et al.  Activation of NG2-positive oligodendrocyte progenitor cells during post-ischemic reperfusion in the rat brain , 2001, Neuroreport.

[6]  P. Rashbass,et al.  Pax6 is required to regulate the cell cycle and the rate of progression from symmetrical to asymmetrical division in mammalian cortical progenitors. , 2002, Development.

[7]  F. Guillemot,et al.  Mash1 regulates neurogenesis in the ventral telencephalon. , 1999, Development.

[8]  H. Okano,et al.  Increased Proliferation of Neural Progenitor Cells but Reduced Survival of Newborn Cells in the Contralateral Hippocampus after Focal Cerebral Ischemia in Rats , 2002, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[9]  M. Chopp,et al.  Cell proliferation and differentiation from ependymal, subependymal and choroid plexus cells in response to stroke in rats , 2002, Journal of the Neurological Sciences.

[10]  K. Nozaki,et al.  Proliferation of neuronal precursor cells in the dentate gyrus is accelerated after transient forebrain ischemia in mice , 1999, Brain Research.

[11]  O. Lindvall,et al.  N‐methyl‐d‐aspartate receptor‐mediated increase of neurogenesis in adult rat dentate gyrus following stroke , 2001, The European journal of neuroscience.

[12]  J. Volpe,et al.  Neurobiology of Periventricular Leukomalacia in the Premature Infant , 2001, Pediatric Research.

[13]  Y. Lu,et al.  Expression of Inducible Nitric Oxide Synthase after Focal Cerebral Ischemia Stimulates Neurogenesis in the Adult Rodent Dentate Gyrus , 2003, The Journal of Neuroscience.

[14]  S. Weiss,et al.  Clonal and population analyses demonstrate that an EGF-responsive mammalian embryonic CNS precursor is a stem cell. , 1996, Developmental biology.

[15]  J. Volpe,et al.  Perinatal brain injury in the preterm and term newborn , 2002, Current opinion in neurology.

[16]  M. Chopp,et al.  Temporal profile of nestin expression after focal cerebral ischemia in adult rat , 1999, Brain Research.

[17]  S. Weiss,et al.  Erythropoietin Regulates the In Vitro and In Vivo Production of Neuronal Progenitors by Mammalian Forebrain Neural Stem Cells , 2001, The Journal of Neuroscience.

[18]  O. Lindvall,et al.  Neuronal replacement from endogenous precursors in the adult brain after stroke , 2002, Nature Medicine.

[19]  David A. Greenberg,et al.  Neurogenesis in dentate subgranular zone and rostral subventricular zone after focal cerebral ischemia in the rat , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[20]  R. Bernabeu,et al.  NMDA and AMPA/Kainate Glutamate Receptors Modulate Dentate Neurogenesis and CA3 Synapsin-I in Normal and Ischemic Hippocampus , 2000, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[21]  Michael Schroeter,et al.  Inflammation and glial responses in ischemic brain lesions , 1998, Progress in Neurobiology.

[22]  F R Sharp,et al.  Increased Neurogenesis in the Dentate Gyrus After Transient Global Ischemia in Gerbils , 1998, The Journal of Neuroscience.

[23]  S. Weiss,et al.  Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. , 1992, Science.

[24]  L. Richards,et al.  De novo generation of neuronal cells from the adult mouse brain. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[25]  S. Weiss,et al.  A multipotent EGF-responsive striatal embryonic progenitor cell produces neurons and astrocytes , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[26]  M. Klagsbrun,et al.  Heparin-Binding Epidermal Growth Factor-Like Growth Factor: Hypoxia-Inducible Expression In Vitro and Stimulation of Neurogenesis In Vitro and In Vivo , 2002, The Journal of Neuroscience.

[27]  M. Moskowitz,et al.  FGF-2 regulation of neurogenesis in adult hippocampus after brain injury , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[28]  E. Parati,et al.  Multipotential stem cells from the adult mouse brain proliferate and self-renew in response to basic fibroblast growth factor , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[29]  K. Abe,et al.  Temporal and spatial differences of PSA-NCAM expression between young-adult and aged rats in normal and ischemic brains , 2001, Brain Research.

[30]  Fred H. Gage,et al.  The Adult Rat Hippocampus Contains Primordial Neural Stem Cells , 1997, Molecular and Cellular Neuroscience.

[31]  W. Pulsinelli,et al.  Transient global ischemia induces dynamic changes in the expression of bFGF and the FGF receptor. , 1994, Brain research. Molecular brain research.

[32]  M. Klagsbrun,et al.  Heparin-binding EGF-like growth factor. , 1997, Biochimica et biophysica acta.

[33]  E. Preston,et al.  Enhanced neurogenesis after transient global ischemia in the dentate gyrus of the rat , 2001, Experimental Brain Research.

[34]  F. Gage,et al.  FGF-2-Responsive Neuronal Progenitors Reside in Proliferative and Quiescent Regions of the Adult Rodent Brain , 1995, Molecular and Cellular Neuroscience.

[35]  T. Yanagihara,et al.  Ischemic damage and subsequent proliferation of oligodendrocytes in focal cerebral ischemia , 1997, Neuroscience.

[36]  Hirofumi Nakatomi,et al.  Regeneration of Hippocampal Pyramidal Neurons after Ischemic Brain Injury by Recruitment of Endogenous Neural Progenitors , 2002, Cell.

[37]  M Chopp,et al.  Proliferation and differentiation of progenitor cells in the cortex and the subventricular zone in the adult rat after focal cerebral ischemia , 2001, Neuroscience.