Death effector activation in the subventricular zone subsequent to perinatal hypoxia/ischemia

Perinatal hypoxia/ischemia (H/I) is the leading cause of neurological injury resulting from birth complications and pre‐maturity. Our studies have demonstrated that this injury depletes the subventricular zone (SVZ) of progenitors. In this study, we sought to reveal which cell death pathways are activated within these progenitors after H/I. We found that calpain activity is detected as early as 4 h of reperfusion and is sustained for 48 h, while caspase 3 activation does not occur until 8 h and peaks at 24 h post‐insult. Activated calpains and caspase 3 co‐localized within precursors situated in the lateral aspects of the SVZ (which coincides with progenitor cell death), whereas neither enzyme was activated in the medial SVZ (which harbors the neural stem cells that are resilient to this insult). These studies reveal targets for neuroprotective agents to protect precursors from cell death towards the goal of restoring normal brain development after H/I.

[1]  N. Plesnila,et al.  Apoptosis-inducing factor is a major contributor to neuronal loss induced by neonatal cerebral hypoxia-ischemia , 2007, Cell Death and Differentiation.

[2]  Li Ni,et al.  Sustained neocortical neurogenesis after neonatal hypoxic/ischemic injury , 2007, Annals of neurology.

[3]  S. Levison,et al.  Hypoxia/ischemia expands the regenerative capacity of progenitors in the perinatal subventricular zone , 2006, Neuroscience.

[4]  Zhengang Yang,et al.  Neural Stem/Progenitor Cells Participate in the Regenerative Response to Perinatal Hypoxia/Ischemia , 2006, The Journal of Neuroscience.

[5]  C. Y. Brazel,et al.  Glutamate enhances survival and proliferation of neural progenitors derived from the subventricular zone , 2005, Neuroscience.

[6]  K. Blomgren,et al.  The influence of age on apoptotic and other mechanisms of cell death after cerebral hypoxia–ischemia , 2005, Cell Death and Differentiation.

[7]  S. Levison,et al.  Neural Stem Cells in the Subventricular Zone are Resilient to Hypoxia/Ischemia whereas Progenitors are Vulnerable , 2004, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[8]  Changlian Zhu,et al.  X-linked inhibitor of apoptosis (XIAP) protein protects against caspase activation and tissue loss after neonatal hypoxia–ischemia , 2004, Neurobiology of Disease.

[9]  S. Rivkees,et al.  A1 adenosine receptors mediate hypoglycemia-induced neuronal injury. , 2004, Journal of molecular endocrinology.

[10]  B. Fredholm,et al.  A1 adenosine receptors mediate hypoxia-induced ventriculomegaly , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[11]  S. Barnoy,et al.  Caspase‐1‐induced calpastatin degradation in myoblast differentiation and fusion: cross‐talk between the caspase and calpain systems , 2003, FEBS letters.

[12]  Changlian Zhu,et al.  Involvement of apoptosis‐inducing factor in neuronal death after hypoxia‐ischemia in the neonatal rat brain , 2003, Journal of neurochemistry.

[13]  R. Neumar,et al.  Cross-talk between Calpain and Caspase Proteolytic Systems During Neuronal Apoptosis* , 2003, The Journal of Biological Chemistry.

[14]  D. Dziewulska,et al.  Cellular expression of tumor necrosis factor a and its receptors in human ischemic stroke. , 2003, Clinical neuropathology.

[15]  S. Estus,et al.  Calpain activates caspase‐3 during UV‐induced neuronal death but only calpain is necessary for death , 2002, Journal of neurochemistry.

[16]  S. Krajewski,et al.  Calpain and Mitochondria in Ischemia/Reperfusion Injury* , 2002, The Journal of Biological Chemistry.

[17]  R. Neumar,et al.  Comparison of Calpain and Caspase Activities in the Adult Rat Brain after Transient Forebrain Ischemia , 2002, Neurobiology of Disease.

[18]  S. Rivkees,et al.  A1 adenosine receptor activation induces ventriculomegaly and white matter loss , 2002, Neuroreport.

[19]  Jun Chen,et al.  Cloning and Characterization of Rat Caspase-9: Implications for a Role in Mediating Caspase-3 Activation and Hippocampal Cell Death after Transient Cerebral Ischemia , 2002, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[20]  K. Blomgren,et al.  Role of Caspase-3 Activation in Cerebral Ischemia-Induced Neurodegeneration in Adult and Neonatal Brain , 2002, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[21]  M. Rudin,et al.  Survival Signaling and Selective Neuroprotection Through Glutamatergic Transmission , 2002, Experimental Neurology.

[22]  D. Ferriero,et al.  Neurodegeneration in the Thalamus following Neonatal Hypoxia-Ischemia Is Programmed Cell Death , 2001, Developmental Neuroscience.

[23]  Susan J. Vannucci,et al.  Hypoxia/Ischemia Depletes the Rat Perinatal Subventricular Zone of Oligodendrocyte Progenitors and Neural Stem Cells , 2001, Developmental Neuroscience.

[24]  Changlian Zhu,et al.  Synergistic Activation of Caspase-3 by m-Calpain after Neonatal Hypoxia-Ischemia , 2001, The Journal of Biological Chemistry.

[25]  K. Blomgren,et al.  Caspase-3 Activation after Neonatal Rat Cerebral Hypoxia-Ischemia , 2001, Neonatology.

[26]  D. Ferriero,et al.  Delayed Neurodegeneration in Neonatal Rat Thalamus after Hypoxia–Ischemia Is Apoptosis , 2001, The Journal of Neuroscience.

[27]  I. Bechmann,et al.  Reactive astrocytes upregulate fas (CD95) and fas ligand (CD95L) expression but do not undergo programmed cell death during the course of anterograde degeneration , 2000, Glia.

[28]  Changlian Zhu,et al.  NMDA blockade attenuates caspase‐3 activation and DNA fragmentation after neonatal hypoxia–ischemia , 2000, Neuroreport.

[29]  K. Blomgren,et al.  Involvement of Caspase-3 in Cell Death after Hypoxia–Ischemia Declines during Brain Maturation , 2000, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[30]  Changlian Zhu,et al.  Correlation Between Caspase‐3 Activation and Three Different Markers of DNA Damage in Neonatal Cerebral Hypoxia‐Ischemia , 2000, Journal of neurochemistry.

[31]  Peng Li,et al.  Direct Cleavage by the Calcium-activated Protease Calpain Can Lead to Inactivation of Caspases* , 2000, The Journal of Biological Chemistry.

[32]  A. Shah,et al.  BDNF Blocks Caspase-3 Activation in Neonatal Hypoxia–Ischemia , 2000, Neurobiology of Disease.

[33]  G. Gao,et al.  N‐terminal cleavage of Bax by calpain generates a potent proapoptotic 18‐kDa fragment that promotes Bcl‐2‐independent cytochrome C release and apoptotic cell death , 2000, Journal of cellular biochemistry.

[34]  S. Levison,et al.  Cycling cells in the adult rat neocortex preferentially generate oligodendroglia , 1999, Journal of neuroscience research.

[35]  Jin-Moo Lee,et al.  The changing landscape of ischaemic brain injury mechanisms , 1999, Nature.

[36]  K. Blomgren,et al.  Calpastatin Is Up-regulated in Response to Hypoxia and Is a Suicide Substrate to Calpain after Neonatal Cerebral Hypoxia-Ischemia* , 1999, The Journal of Biological Chemistry.

[37]  Sten Orrenius,et al.  Cleavage of the calpain inhibitor, calpastatin, during apoptosis , 1998, Cell Death and Differentiation.

[38]  John Calvin Reed,et al.  Bax cleavage is mediated by calpain during drug-induced apoptosis , 1998, Oncogene.

[39]  K. Wang,et al.  Caspase-mediated fragmentation of calpain inhibitor protein calpastatin during apoptosis. , 1998, Archives of biochemistry and biophysics.

[40]  A. Shah,et al.  Caspase inhibitor affords neuroprotection with delayed administration in a rat model of neonatal hypoxic-ischemic brain injury. , 1998, The Journal of clinical investigation.

[41]  C. Portera-Cailliau,et al.  Non‐NMDA and NMDA receptor‐mediated excitotoxic neuronal deaths in adult brain are morphologically distinct: Further evidence for an apoptosis‐necrosis continuum , 1997, The Journal of comparative neurology.

[42]  R. Vannucci,et al.  Effects of Hypoxia-Ischemia on GLUT1 and GLUT3 Glucose Transporters in Immature Rat Brain , 1996, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[43]  J. Szaflarski,et al.  Cerebral hypoxia-ischemia stimulates cytokine gene expression in perinatal rats. , 1995, Stroke.

[44]  G. Lynch,et al.  Induction of calpain-mediated spectrin fragments by pathogenic treatments in long-term hippocampal slices. , 1995, The Journal of pharmacology and experimental therapeutics.

[45]  J. Rice,et al.  The influence of immaturity on hypoxic‐ischemic brain damage in the rat , 1981, Annals of neurology.