TRANSIENT CEREBRAL-ISCHEMIA DECREASES CALCIUM CALMODULIN-DEPENDENT PROTEIN-KINASE-II IMMUNOREACTIVITY, BUT NOT MESSENGER-RNA LEVELS IN THE GERBIL HIPPOCAMPUS

During transient cerebral ischemia, intracellular calcium increases in itiating a cascade of events which leads to the delayed death of neuro ns located in the hippocampus. Coupled to this calcium disturbance is the rapid decrease of calcium/calmodulin kinase II (CaM kinase) activi ty, a protein kinase critical to neuronal functioning. The present stu dy correlated the increased locomotor activity following ischemic insu lt with alterations in CaM kinase mRNA levels and immunocytochemical l abeling of alpha and beta CaM kinase subunits in the hippocampus. The protective effect of hypothermia was also compared with CaM kinase mRN A levels and immunoreactivity. Levels of CaM kinase message for either alpha or beta subunits was not altered in ischemic gerbils compared t o sham or hypothermic ischemic conditions. Immunoreactivity for both t he alpha and beta subunits was markedly reduced in the vulnerable CA1 region of ischemic animals compared to sham controls. Gerbils that und erwent the ischemic insult while hypothermic showed no decrement in st aining. CaM kinase-like immunoreactivity in the ischemia-resistant CA3 sector was not altered following ischemia. These data suggest that th e loss of hippocampal CaM kinase immunoreactivity observed at 24 h fol lowing ischemia is not associated with a reduction in CaM kinase mRNA levels and support the notion that the rapid decline in CaM kinase act ivity following ischemic insult is a result of a posttranslational mod ification and/or translocation of the enzyme.