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A Model of Ischemia-Induced Neuroblast Activation in the Adult Subventricular Zone

By Davide Vergni, Filippo Castiglione, Maya Briani, Silvia Middei, Elena Alberdi, Klaus G. Reymann, Roberto Natalini, Cinzia Volonté, Carlos Matute and Fabio Cavaliere


We have developed a rat brain organotypic culture model, in which tissue slices contain cortex-subventricular zone-striatum regions, to model neuroblast activity in response to in vitro ischemia. Neuroblast activation has been described in terms of two main parameters, proliferation and migration from the subventricular zone into the injured cortex. We observed distinct phases of neuroblast activation as is known to occur after in vivo ischemia. Thus, immediately after oxygen/glucose deprivation (6–24 hours), neuroblasts reduce their proliferative and migratory activity, whereas, at longer time points after the insult (2 to 5 days), they start to proliferate and migrate into the damaged cortex. Antagonism of ionotropic receptors for extracellular ATP during and after the insult unmasks an early activation of neuroblasts in the subventricular zone, which responded with a rapid and intense migration of neuroblasts into the damaged cortex (within 24 hours). The process is further enhanced by elevating the production of the chemoattractant SDf-1α and may also be boosted by blocking the activation of microglia. This organotypic model which we have developed is an excellent in vitro system to study neurogenesis after ischemia and other neurodegenerative diseases. Its application has revealed a SOS response to oxygen/glucose deprivation, which is inhibited by unfavorable conditions due to the ischemic environment. Finally, experimental quantifications have allowed us to elaborate a mathematical model to describe neuroblast activation and to develop a computer simulation which should have promising applications for the screening of drug candidates for novel therapies of ischemia-related pathologies

Topics: Research Article
Publisher: Public Library of Science
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Provided by: PubMed Central

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  3. (2000). Agonists and antagonists acting at P2X receptors: selectivity profiles and functional implications.
  4. (2007). Alvarez-Buylla A
  5. (2006). Anti-inflammatory treatment in oxygen-glucose-deprived hippocampal slice cultures is neuroprotective and associated with reduced cell proliferation and intact neurogenesis.
  6. (2007). ATP modulates cell proliferation and elicits two different electrophysiological responses in human mesenchymal stem cells.
  7. (2007). Calcium signaling in vertebrate embryonic patterning and morphogenesis.
  8. (2008). CD133+ neural stem cells in the ependyma of mammalian postnatal forebrain.
  9. (2004). Dopaminergic nigrostriatal projections regulate neural precursor proliferation in the adult mouse subventricular zone.
  10. (1999). Excitotoxic effects of non-NMDA receptor agonists in organotypic corticostriatal slice cultures.
  11. (2007). Experimental treatments for acute ischaemic stroke.
  12. (1992). Flow Cytometry.
  13. (2004). Functional significance of adult neurogenesis.
  14. (2007). Glia-like stem cells sustain physiologic neurogenesis in the adult mammalian carotid body.
  15. (2001). Glucose deprivation and chemical hypoxia: neuroprotection by P2 receptor antagonists.
  16. (2008). Hedgehog signaling and primary cilia are required for the formation of adult neural stem cells.
  17. (2005). Identification and characterization of two neurogenic zones in interface organotypic hippocampal slice cultures.
  18. (2002). Identification of neural stem cells in the adult vertebrate brain.
  19. (2000). Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP.
  20. (2002). Increased proliferation of neural progenitor cells but reduced survival of newborn cells in the contralateral hippocampus after focal cerebral ischemia in rats.
  21. (1993). Inducible nitric oxide synthase activity of cloned murine microglial cells.
  22. (1999). Markers for neuronal degeneration in organotypic slice cultures.
  23. (1998). Mathematical physiology.
  24. (1997). Mechanism of migration of olfactory bulb interneurons.
  25. (2008). Mechanisms and functional implications of adult neurogenesis.
  26. (2006). Microglia provide neuroprotection after ischemia.
  27. (2005). Microglia response and P2 receptor participation in oxygen/glucose deprivation-induced cortical damage.
  28. (2007). Neuroblast division during migration toward the ischemic striatum: a study of dynamic migratory and proliferative characteristics of neuroblasts from the subventricular zone.
  29. (2004). Neurogenic and intact or apoptotic nonneurogenic areas of adult brain release diffusible molecules that differentially modulate the development of subventricular zone cell cultures.
  30. (2002). Opinion: neural stem cell therapy for neurological diseases: dreams and reality.
  31. (1996). Organotypic cortex-striatum-mesencephalon cultures: the nigrostriatal pathway.
  32. (2007). P2 receptor antagonist trinitrophenyl-adenosine-triphosphate protects hippocampus from oxygen and glucose deprivation cell death.
  33. (2008). Patterns of neurogenesis and amplitude of Reelin expression are essential for making a mammalian-type cortex.
  34. Pe ´rez-Cerda ´F ,P e ´rez-Samartı ´n A, Alberdi E, et al. (2007) P2X(7) receptor blockade prevents ATP excitotoxicity in oligodendrocytes and ameliorates experimental autoimmune encephalomyelitis.
  35. (2005). Pringle A
  36. (2002). Proliferating cells differentiate into neurons in the hippocampal CA1 region of gerbils after global cerebral ischemia.
  37. (2008). Proliferating progenitor cells: a required cellular element for induction of ischemic tolerance in the brain.
  38. (2007). Protease-activated receptor-1 induces generation of new microglia in the dentate gyrus of traumatised hippocampal slice cultures.
  39. (2007). Purinergic receptor activation inhibits mitogen-stimulated proliferation in primary neurospheres from the adult mouse subventricular zone.
  40. (2007). Regeneration of the central nervous system using endogenous repair mechanisms.
  41. (2006). Regulation of strokeinduced neurogenesis in adult brain–recent scientific progress.
  42. Shetty AK (2008) Behavior of neural stem cells in the Alzheimer brain.
  43. (1994). Spontaneous pyramidal cell death in organotypic slice cultures from rat hippocampus is prevented by glutamate receptor antagonists.
  44. (2007). Stem cells act through multiple mechanisms to benefit mice with neurodegenerative metabolic disease.
  45. (2006). Temporally specific proliferation events are induced in the hippocampus following acute focal injury.
  46. (2007). The ectonucleotidases alkaline phosphatase and nucleoside triphosphate diphosphohydrolase 2 are associated with subsets of progenitor cell populations in the mouse embryonic, postnatal and adult neurogenic zones.
  47. (2008). The recently identified P2Y-like receptor GPR17 is a sensor of brain damage and a new target for brain repair.
  48. (2008). The role of ATP signaling in the migration of intermediate neuronal progenitors to the neocortical subventricular zone.
  49. (2006). The subventricular zone releases factors which can be protective in oxygen/glucose deprivation-induced cortical damage: an organotypic study.
  50. (2006). The therapeutic potential of adult neural stem cells.
  51. (2006). The therapeutic potential of neural stem cells.

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