Changes in mRNA for ryanodine receptors after transient cerebral ischemia and tolerance induction

Disturbance of Ca2+ homeostasis is assumed to precede ischemia-induced neur onal death. Using the 4-vessel occlusion model of cerebral ischemia and ind uction of ischemic tolerance in the rat, we studied the intracellular Ca2activated Ca2+ channel, the ryanodine receptor (RyR), by means of in situ h ybridisation and immunohistochemistry. We found the level of RyR2 mRNA incr eased in CAI and CA3 of the ischemic vulnerable hippocampus following 3 min utes of tolerance inducing ischemia, whereas 9 minutes of ischemia lead to an increased mRNA level in CA1 in contrast to a decrease in CA3. In ischemi c tolerant animals (3 + 8.5 minutes of ischemia) the mRNA level was decreas ed in CA3. In all experimental groups, RyR1 mRNA remained unaltered, wherea s RyR3 mRNA decreased in DG. Immunohistochemistry revealed no alterations o f the RyR protein level in all the ischemic groups compared to sham-operate d animals. Taken together, these changes do not clarify if the RyR is invol ved in tolerance induction or in the degenerative process leading to ischem ic delayed neuronal death.