Baclofen is neuroprotective and prevents loss of calcium/calmodulin-dependent protein kinase II immunoreactivity in the ischemic gerbil hippocampus.

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 gamma-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.