title: NR2B subunit exerts a critical role in postischemic synaptic plasticity.
abstract: OBJECTIVE
  We characterized the differential effect of the NR2B subunit antagonist ifenprodil in the induction of activity-dependent long-term potentiation (LTP) and of postischemic LTP as well as in the neuronal damage induced by focal ischemia.
  
  
  METHODS
  Intracellular recordings were obtained from rat corticostriatal slice preparations. High-frequency stimulation of corticostriatal fibers was used as a LTP-inducing protocol. In vitro ischemia was induced by oxygen and glucose deprivation. In vivo ischemia was induced by permanent middle cerebral artery occlusion. Intracellular recordings were also performed in the ischemic penumbra.
  
  
  RESULTS
  Antagonists selectively targeting N-methyl-d-aspartate receptors containing the NR2B subunit blocked postischemic LTP without affecting activity-dependent LTP. In a model of focal ischemia, blockade of NR2B subunit in vivo caused reduction of brain damage, amelioration of neurological outcome, and normalization of the synaptic levels of NR2B subunits. Moreover, the antagonism of NR2B subunit was able to rescue the activity-dependent LTP in the ischemic penumbra.
  
  
  CONCLUSIONS
  We suggest that NR2B subunits contribute to the striatal damage caused by in vivo and in vitro ischemia and play a critical role in the induction of postischemic LTP as well as in the suppression of activity-dependent LTP in the ischemic penumbra.
authors.affiliation: Laboratorio di Neurofisiologia, Fondazione Santa Lucia, Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Picconi
authors.forename: Anna
authors.initials: A
authors.lastname: Tortiglione
authors.forename: Ilaria
authors.initials: I
authors.lastname: Barone
authors.forename: Diego
authors.initials: D
authors.lastname: Centonze
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Gardoni
authors.forename: Paolo
authors.initials: P
authors.lastname: Gubellini
authors.forename: Paola
authors.initials: P
authors.lastname: Bonsi
authors.forename: Antonio
authors.initials: A
authors.lastname: Pisani
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bernardi
authors.forename: Monica
authors.initials: M
authors.lastname: Di Luca
authors.forename: Paolo
authors.initials: P
authors.lastname: Calabresi
mesh_terms: D000818:Animals; D001925:Brain Damage, Chronic / Q000209:etiology / Q000517:prevention & control; D002544:Cerebral Infarction / Q000473:pathology; D002560:Cerebrovascular Circulation; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; C121001:NR2B NMDA receptor; D018696:Neuroprotective Agents; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C095106:traxoprodil mesylate; C010739:ifenprodil