Early and delayed induction of immediate early gene expression in a novel focal cerebral ischemia model in the rat.
This study aimed at evaluating changes in expression of immediate early genes in a new photothrombotic focal ischemia model that exhibits late spontaneous reperfusion and morphological restoration in the region-at-risk within the cerebral cortex. Gene expression was studied with Northern blots, in situ hybridization and immunohistochemistry. At early time points (1-4 h), nerve growth factor-induced gene A and B, and c-fos mRNAs, were quickly induced throughout the ipsilateral cortex, with no obvious differences between the region-at-risk and remote cortical areas. High concentrations of nerve growth factor-induced gene A and c-Fos proteins were present within the region-at-risk even when cortical cerebral blood flow was as low as 40% of control values. At 4 h the nerve growth factor-induced gene A mRNA and protein expression was significantly decreased in the hippocampus vs. naive controls. However, a small decrease was also found in sham-operated and anaesthetized controls. A late induction, at 5 days, of c-fos and nerve growth factor-induced gene B mRNAs was seen bilaterally in the hippocampus and also, in the case of nerve growth factor induced-gene B, in the contralateral cortex. A complex pattern of changes in immediate early gene expression occurs after reversible focal cortical ischemia. This may be important for tissue recovery as well as neuropsychiatric symptoms after stroke.
Johansson
I M
IM
Department of Public Health and Clinical Medicine, Medicine, Umeâ University Hospital, SE-901 85 Umeâ, Sweden.
Wester
P
P
Háková
M
M
Gu
W
W
Seckl
J R
JR
Olsson
T
T
D000818:Animals; D002545:Brain Ischemia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D051766:Early Growth Response Protein 1; D005786:Gene Expression Regulation / Q000502:physiology*; D017781:Genes, Immediate-Early / Q000235:genetics*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017874:Immediate-Early Proteins; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; C539820:Nr4a1 protein, rat; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors