N-methyl-D-aspartate receptor-mediated increase of neurogenesis in adult rat dentate gyrus following stroke

Eur J Neurosci. 2001 Jul;14(1):10-8. doi: 10.1046/j.0953-816x.2001.01611.x.


Neurogenesis in the adult rat dentate gyrus was studied following focal ischemic insults produced by middle cerebral artery occlusion (MCAO). Animals were subjected to either 30 min of MCAO, which causes damage confined to the striatum, or 2 h of MCAO, which leads to both striatal and cortical infarction. When compared to sham-operated rats, MCAO-rats showed a marked increase of the number of cells double-labelled for 5-bromo-2'-deoxyuridine-5'-monophosphate (BrdU; injected during 4-6 days postischemia) and neuronal-specific antigen (NeuN; a marker of postmitotic neurons) in the ipsilateral dentate granule cell layer and subgranular zone at 5 weeks following the 2 h insult. Only a modest and variable increase of BrdU-labelled cells was found after 30 min of MCAO. The enhanced neurogenesis was not dependent on cell death in the hippocampus, and its magnitude was not correlated to the degree of cortical damage. Systemic administration of the N-methyl-D-aspartate (NMDA) receptor blocker dizocilpine maleate (MK-801) completely suppressed the elevated neurogenesis following 2 h of MCAO. Our findings indicate that stroke leads to increased neurogenesis in the adult rat dentate gyrus through glutamatergic mechanisms acting on NMDA receptors. This modulatory effect may be mediated through changes in the levels of several growth factors, which occur after stroke, and could influence various regulatory steps of neurogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimetabolites / pharmacokinetics
  • Biomarkers / analysis
  • Brain Ischemia / metabolism
  • Brain Ischemia / pathology
  • Brain Ischemia / physiopathology
  • Bromodeoxyuridine / pharmacokinetics
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Cell Division / drug effects
  • Cell Division / physiology*
  • Dentate Gyrus / cytology
  • Dentate Gyrus / growth & development*
  • Dentate Gyrus / metabolism
  • Excitatory Amino Acid Antagonists / pharmacology
  • Immunohistochemistry
  • Infarction, Middle Cerebral Artery / metabolism*
  • Infarction, Middle Cerebral Artery / pathology
  • Infarction, Middle Cerebral Artery / physiopathology
  • Male
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Recovery of Function / drug effects
  • Recovery of Function / physiology


  • Antimetabolites
  • Biomarkers
  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Bromodeoxyuridine