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Baclofen is neuroprotective and prevents loss of calcium/calmodulin‐dependent protein kinase II immunoreactivity in the ischemic gerbil hippocampus
Author(s) -
Babcock Alex M.,
Everingham Andi,
Paden Charles M.,
Kimura Maki
Publication year - 2002
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10169
Subject(s) - neuroprotection , glutamate receptor , baclofen , gerbil , hippocampus , excitotoxicity , hippocampal formation , pharmacology , neuroscience , protein kinase a , medicine , agonist , ischemia , chemistry , kinase , biology , biochemistry , receptor
Excessive release of glutamate during transient cerebral ischemia initiates a cascade of events that leads to the delayed and selective death of neurons located in the hippocampus. Activity of calcium calmodulin kinase II (CaM kinase), a protein kinase critical to neuronal functioning, disappears following ischemia. The in vivo link between glutamate excitoxicity and alterations in CaM kinase activity has not been extensively studied. Baclofen, a selective γ‐aminobutyric acid (GABA) B receptor agonist, has been shown to inhibit glutamate release. The present study evaluated the neuroprotective efficacy of this compound and assessed early changes in hippocampal‐dependent behaviors and CaM kinase immunoreactivity following transient cerebral ischemia. Baclofen (50 mg/kg) prevented both the loss of hippocampal CA1 pyramidal cells and the reduction in hippocampal CaM kinase immunoreactivity observed in control animals following ischemic insult. Cerebral ischemia produced a significant increase in working memory errors; however, baclofen failed to attenuate this memory deficit. Results confirm that baclofen is neuroprotective and support a link between glutamate excitotoxicity and reductions in CaM kinase immunoreactivity. © 2002 Wiley‐Liss, Inc.