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(Stroke. 2006;37:1895.)
© 2006 American Heart Association, Inc.

Original Contributions

NR2B Subunit Exerts a Critical Role in Postischemic Synaptic Plasticity

Barbara Picconi, PhD; Anna Tortiglione, PhD; Ilaria Barone, PhD; Diego Centonze, MD; Fabrizio Gardoni, PhD; Paolo Gubellini, PhD; Paola Bonsi, PhD; Antonio Pisani, MD; Giorgio Bernardi, MD; Monica Di Luca, MD Paolo Calabresi, MD

From Laboratorio di Neurofisiologia, Fondazione Santa Lucia, Rome (B.P., A.T., I.B., D.C., P.B., A.P., G.B., P.C.); Clinica Neurologica, Dipartimento Neuroscienze, University of Rome Tor Vergata, Rome (D.C., P.G., A.P., G.B.); Center of Excellence on Neurodegenerative Diseases and Department of Pharmacological Sciences, University of Milan, Milano (F.G., M. Di L.); and Clinica Neurologica, Dipartimento Specialità Medico Chirurgiche e Sanità Pubblica, Università di Perugia, Ospedale Silvestrini, Perugia (P.C.), Italy.

Correspondence to Paolo Calabresi, MD, Clinica Neurologica, Dipartimento Specialità Medico Chirurgiche e Sanità Pubblica, Università di Perugia, Perugia, Italy. E-mail calabre{at}unipg.it

Background and Purpose— 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.

Key Words: corpus striatum • electrophysiology • ischemia • middle cerebral artery occlusion • receptors, N-methyl-D-aspartate • synapses

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