BIPHASIC EXPRESSION OF THE FOS AND JUN FAMILIES OF TRANSCRIPTION FACTORS FOLLOWING TRANSIENT FOREBRAIN ISCHEMIA IN THE RAT - EFFECT OF HYPOTHERMIA

Transient global ischaemia induces the expression of immediate early g enes. Using in situ hybridization, the expression of c-fos, fosB, fra- 1, fra-2, c-jun and junB was studied after 15 min of normothermic and hypothermic (33 degrees C) transient forebrain ischaemia in the rat, i nduced by common carotid occlusion combined with systemic hypotension. Two phases of induction of the immediate early genes were observed. T he early phase, peaking at 1-2 h of reperfusion, was dominated by mark ed expression in the dentate gyrus. The second phase, with maximal exp ression at 12-36 h of reperfusion, was observed particularly in the vu lnerable CA1 and CA3 regions. Hypothermia increased the early inductio n of one of the genes studied, signifying a differential effect of hyp othermia upon the signal transduction mechanisms activating these gene s. The late induction occurred earlier after hypothermic than after no rmothermic ischaemia. The early expression of immediate early genes is due to the rapid activation of cytosolic response elements caused by the ischaemic insult. We suggest that the late induction is a stress s ignal for activation of repair processes, analogous to the cellular re sponse seen after UV light-induced DNA damage. The relatively fast ind uction of the immediate early genes following hypothermic ischaemia ma y reflect a faster resumption of normal intracellular signalling, enha ncing neuronal recovery.