Ciliary neurotrophic factor (
CNTF) is a member of
cytokines, with trophic effects on ciliary, motor sympathetic, sensory,
retinal and hippocampal neurons. In the present study, we examined the temporal and spatial expression profiles of
CNTF and
CNTF receptor alpha (CNTFR alpha) mRNAs in a focal
cerebral ischemia model induced by transient occlusion of the right middle cerebral artery and both common carotid arteries. Northern blot analysis showed a slow and sustained increase in the 1.2 kb transcript of
CNTF mRNA in the ischemic cortex of rats subjected to a transient 60 min ischemic insult. A delayed decrease in the 2.1 kb transcript of CNTFR alpha
mRNA in the ischemic cortex was observed in rats subjected to 60 min
ischemia followed by 72 h of reperfusion. In situ hybridization studies revealed constitutive expression of CNTFR alpha
mRNA in the majority of neurons in the brain. Following 4 h of reperfusion, increased expression of CNTFR alpha
mRNA was observed in the ipsilateral dentate gyrus, which is opposite to the down-regulation noted in the ischemic cortex. Within the
infarct area CNTFR alpha
mRNA had a marked increase in cortical layer II but a decrease in cortical layer V following 1 day of reperfusion. No signal of CNTFR alpha
mRNA was detected within the
infarct region following 3 days of reperfusion. Following 1 week of reperfusion, although no marked changes was observed in the level of CNTFR alpha
mRNA in the area immediately surrounding the
necrosis region where the reactive astrocytes were noted, a striking increase in the
CNTF mRNA signal was noted. In summary, differential regulation of
CNTF and CNTFR alpha mRNAs was noted in the ischemic cortex. Regional differences in
CNTF receptor expression were noted between the ischemic cortex and ipsilateral dentate gyrus as well as between cortical layer II and V within the
infarct region.
CNTF mRNA, but not CNTFR alpha
mRNA, had a marked increase in the area immediately adjacent to the
necrosis. The mechanisms and patho-physiological significance for these differential regulation remain to be studied.