Microarray analysis of acute and delayed gene expression profile in rats after focal ischemic brain injury and reperfusion.
Temporal changes in gene expression were measured using DNA microarrays after 30-min or 2-hr transient middle cerebral artery occlusion (MCAo) in rats. Total RNA was extracted from the injured hemisphere at 30 min, 4 hr, 8 hr, 24 hr, 3 days, and 7 days after MCAo for GeneChip analysis using Affymetrix U34 Rat Neurobiology arrays (1,322 functional genes). In total, 267 genes were expressed differentially: 166 genes were upregulated, 94 genes were downregulated, and 7 genes were biphasically up- and downregulated. Among all differentially expressed genes, 88 were newly identified as associated with ischemic brain injury. Most affected genes were distributed among 12 functional categories. Immediate early genes, transcription factors, and heat shock proteins were upregulated as early as 30 min after MCAo, followed by the upregulation of inflammation, apoptosis, cytoskeletal, and metabolism genes, which peaked within 4-24 hr of injury. Neurotrophic growth factors exhibited a sustained upregulation beginning 24 hr after MCAo and persisting through 7 days post-injury. Three classes of genes were downregulated with distinct temporal patterns: ion channel genes and neurotransmitter receptor genes were downregulated between 8-24 hr after injury, whereas synaptic proteins genes were downregulated between 3-7 days after MCAo. Downregulation of synaptic protein gene expression after ischemic injury is of particular interest because of its conspicuously delayed pattern as a functional group, which has not been reported previously and may play a role in post-injury recovery.
Lu
X-C May
XC
Division of Neuroscience, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910, USA. May.Lu@na.amedd.army.mil
Williams
Anthony J
AJ
Yao
Changping
C
Berti
Rossana
R
Hartings
Jed A
JA
Whipple
Rebecca
R
Vahey
Maryanne T
MT
Polavarapu
Ratna G
RG
Woller
Kimberly L
KL
Tortella
Frank C
FC
Dave
Jitendra R
JR
D000818:Animals; D002545:Brain Ischemia / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000235:genetics* / Q000378:metabolism