Delayed genomic responses to transient middle cerebral artery occlusion in the rat.
Ischemic stress in the brain induces acute and massive neuronal death in the targeted area, which is followed by a second round of detrimental processes, called delayed neuronal death, in the neighboring areas. To test the hypothesis that transcriptional control plays a role in the pathophysiology of the postischemic brain, the genomic responses that occurred in the brain at 3, 6 and, 12 h, and 1, 2 or 4 days after transient middle cerebral artery occlusion (MCAO) were examined using a microarray harboring 5000 rat cDNAs. This analysis indicated that the number of up-regulated genes was gradually increased, along with the concomitant reduction in the number of down-regulated genes, until 12 h to 1 day after MCAO. It was followed by a delayed surge of down-regulated genes at 2 days after MCAO. Northern blots and immunohistological analysis confirmed the validity of these microarray data. We present a list of 85 genes that were up-regulated more than 2.3-fold between 12 h and 4 days after MCAO, which included 56 novel genes whose expression has not previously been implicated in ischemic pathophysiology. The list included genes involved in oxidative stress, inflammation, extracellular matrix (ECM), neuronal development and differentiation processes. Together these results suggest that the pathophysiology of the postischemic brain proceeds by the transcriptional activation of genes related to the process of delayed neuronal damage and/or recovery and repair.
Kim
Jung-Bin
JB
Department of Anatomy, Inha University School of Medicine, 7-241 Shinheung-dong, Jung-Gu, Inchon 400-712, Korea.
Piao
Chun-Shu
CS
Lee
Kang Woo
KW
Han
Pyung-Lim
PL
Ahn
Joon Ik
JI
Lee
Yong Sung
YS
Lee
Ja-Kyeong
JK
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D015152:Blotting, Northern; D016923:Cell Death; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D015536:Down-Regulation; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020869:Gene Expression Profiling / Q000379:methods / Q000706:statistics & numerical data*; D005947:Glucose / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015854:Up-Regulation
D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496052:Ptk2 protein, rat; D005947:Glucose