Region-specific role for GluN2B-containing NMDA receptors in injury to Purkinje cells and CA1 neurons following global cerebral ischemia. (22nd January 2015)

• Record Type: Journal Article
• Authors: Quillinan, N.; Grewal, H.; Deng, G.; Shimizu, K.; Yonchek, J.C.; Strnad, F.; Traystman, R.J.; Herson, P.S.
• Is Part Of: Neuroscience. Volume 284(2015)
• Page Start: 555
• Page End: 565
• Publication Date: 2015-01-22
• Subjects: ACSF artificial cerebral spinal fluid -- ANOVA analysis of variance -- CA/CPR cardiac arrest and cardiopulmonary resuscitation -- CREB cAMP response element-binding -- EGTA ethylene glycol tetraacetic acid -- H&E hematoxylin and eosin -- HEPES 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid -- LCM laser capture microdissection -- MK-801 dizocilpine -- NMDA N-methyl-d-aspartic acid -- PCs Purkinje cells -- PFA paraformaldehyde -- RT-PCR reverse transcription polymerase chain reaction -- TUNEL terminal deoxynucleotidyl transferase dUTP nick end labeling; cardiac arrest -- excitotoxicity -- global ischemia -- Purkinje cells -- NMDA; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2014.10.033
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Immunohistochemistry and cell density analysis of ischemic injury in cerebellum. Purkinje cell death rapid and not via apoptosis following CA/CPR. GluN2B antagonist selectively protects CA1 neurons. Abstract: Motor deficits are present in cardiac arrest survivors and injury to cerebellar Purkinje cells (PCs) likely contribute to impairments in motor coordination and post-hypoxic myoclonus. N-Methyl-d -aspartic acid (NMDA) receptor-mediated excitotoxicity is a well-established mechanism of cell death in several brain regions, but the role of NMDA receptors in PC injury remains understudied. Emerging data in cortical and hippocampal neurons indicate that the GluN2A-containing NMDA receptors signal to improve cell survival and GluN2B-containing receptors contribute to neuronal injury. This study compared neuronal injury in the hippocampal CA1 region to that in PCs and investigated the role of NMDA receptors in PC injury in our mouse model of cardiac arrest and cardiopulmonary resuscitation (CA/CPR). Analysis of cell density demonstrated a 24% loss of PCs within 24 h after 8 min CA/CPR and injury stabilized to 33% by 7 days. The subunit promiscuous NMDA receptor antagonist MK-801 protected both CA1 neurons and PCs from ischemic injury following CA/CPR, demonstrating a role for NMDA receptor activation in injury to both brain regions. In contrast, the GluN2B antagonist, Co 101244, had no effect on PC loss while protecting against injury in the CA1 region. These data indicate that ischemic injury to cerebellar PCs progresses via different cell death mechanisms compared to hippocampal CA1 neurons.