A microarray study of gene and protein regulation in human and rat brain following middle cerebral artery occlusion.
BACKGROUND
Altered gene expression is an important feature of ischemic cerebral injury and affects proteins of many functional classes. We have used microarrays to investigate the changes in gene expression at various times after middle cerebral artery occlusion in human and rat brain.


RESULTS
Our results demonstrated a significant difference in the number of genes affected and the time-course of expression between the two cases. The total number of deregulated genes in the rat was 335 versus 126 in the human, while, of 393 overlapping genes between the two array sets, 184 were changed only in the rat and 36 in the human with a total of 41 genes deregulated in both cases. Interestingly, the mean fold changes were much higher in the human. The expression of novel genes, including p21-activated kinase 1 (PAK1), matrix metalloproteinase 11 (MMP11) and integrase interactor 1, was further analyzed by RT-PCR, Western blotting and immunohistochemistry. Strong neuronal staining was seen for PAK1 and MMP11.


CONCLUSIONS
Our findings confirmed previous studies reporting that gene expression screening can detect known and unknown transcriptional features of stroke and highlight the importance of research using human brain tissue in the search for novel therapeutic agents.
Mitsios
Nick
N
School of Biology, Chemistry and Health Science, John Dalton Building, Manchester Metropolitan University, Chester Street, Manchester, UK. n.mitsios@mmu.ac.uk
Saka
Mohamad
M
Krupinski
Jerzy
J
Pennucci
Roberta
R
Sanfeliu
Coral
C
Wang
Qiuyu
Q
Rubio
Francisco
F
Gaffney
John
J
Kumar
Pat
P
Kumar
Shant
S
Sullivan
Matthew
M
Slevin
Mark
M
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005333:Fetus; D005786:Gene Expression Regulation / Q000502:physiology*; D005947:Glucose / Q000172:deficiency; D006801:Humans; D000860:Hypoxia / Q000209:etiology / Q000401:mortality; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D053507:Matrix Metalloproteinase 11 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D000071796:SMARCB1 Protein; D020521:Stroke / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors; D054462:p21-Activated Kinases; D053507:Matrix Metalloproteinase 11; D005947:Glucose