NEUROPROTECTIVE EFFECTS OF DEXMEDETOMIDINE IN THE GERBIL HIPPOCAMPUS AFTER TRANSIENT GLOBAL-ISCHEMIA

Background: Cerebral ischemia induces a massive release of norepinephr ine associated with neuronal death in the brain, It has been demonstra ted that alpha(2)-adrenoceptor agonists decrease the release and turno ver of noradrenaline, and this might prove advantageous in counteracti ng the neurodegeneration in ischemic brain, Therefore, in the present study, the authors tested whether dexmedetomidine, a selective alpha(2 )-receptor agonist, has neuroprotective effects in a gerbil transient global ischemia model. Methods: Ischemia was induced by bilateral caro tid occlusion for 5 min in diethylether-anesthetized normothermic gerb ils, Dexmedetomidine was administered subcutaneously in four different treatment paradigms (6-8 animals/group): 3 or 30 mu g/kg 30 min befor e and thereafter at 3, 12, 24, and 48 h after the occlusion, or 3 or 3 0 mu g/kg at 3, 12, 24, and 48 h after the occlusion, Control animals were subjected to forebrain ischemia but received only saline injectio ns. One week after occlusion, animals were transcardially perfused for histochemistry, Neuronal death in the CA1 and CA3 regions of the hipp ocampus and in the hilus of the dentate gyrus was evaluated in silver- stained 60-mu m coronal sections. Results: Compared with saline-treate d ischemic animals, dexmedetomidine at a dose of 3 mu g/kg given befor e and continued after the induction of ischemia reduced the number of damaged neurons in the CA3 area (2 +/- 3 vs. 17 +/- 20 degenerated neu rons/mm(2); P < 0.05). Also in the dentate hilus, the number of damage d neurons was reduced by dexmedetomidine (3 mu g/kg) given before and continued after ischemia (5 +/- 7 vs. 56 +/- 42 degenerated neurons/mm (2); P < 0.01). Conclusions: The present data demonstrate that dexmede tomidine effectively prevents delayed neuronal death in CA3 area and i n the dentate hilus in gerbil hippocampus when the management is start ed before the onset of ischemia and continued for 48 h after reperfusi on, Inhibition of ischemia-induced norepinephrine release may be assoc iated with neuroprotection by dexmedetomidine.