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.