Effects of hypoxia-ischemia and seizures on neuronal and glial-like c-fos protein levels in the infant rat.
Unilateral carotid ligation in immature rats, followed by 2 h of hypoxia led to ischemic cell change from 2 h after the insult, on the ligated side of the brain. There was a time-dependent induction of immunoreactive c-fos protein in neurones but not glia or ependyma on the non-ligated side of the brain. Induction only occurred in rats that had seizures post hypoxia-ischemia. In the ligated hemisphere c-fos protein was induced in glial-like cells in the corpus callosum, fornix/fimbria and internal capsule and in ependymal cells lining the lateral ventricle starting from 2 h after hypoxia but subsiding by 3 days. No neuronal c-fos induction was seen in areas showing neuronal damage. MK-801 or carbamazepine, which prevented hypoxia-ischemia-induced seizures, also prevented c-fos induction in the non-ligated hemisphere while MK-801 was associated with increased c-fos induction in hippocampal neurones from the ligated side, as well as in glial-like and ependymal cells. These results suggest several processes are involved following the hypoxic-ischemic insult. Firstly, severe hypoxia-ischemia is associated with a reduction in neuronal c-fos protein levels, probably as a result of neuronal failure and death. Secondly, post hypoxic seizures cause c-fos induction in surviving neurones. Thirdly, glial-like from regions in which there is neural loss also exhibit induction of c-fos, which may be important for their subsequent proliferation or for the production of growth factors.
Gunn
A J
AJ
Department of Paediatrics, School of Medicine, University of Auckland, New Zealand.
Dragunow
M
M
Faull
R L
RL
Gluckman
P D
PD
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D006651:Histocytochemistry; D002534:Hypoxia, Brain / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009928:Organ Specificity; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos; D011519:Proto-Oncogenes; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000378:metabolism*
D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D011505:Protein-Tyrosine Kinases