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Updated: Aug 22, 2026
2-Vessel Occlusion/Hypotension: A Rat Model of Global Brain Ischemia
Published on: June 22, 2013
Microarray analysis of acute and delayed gene expression profile in rats after focal ischemic brain injury and
X-C May Lu1, Anthony J Williams, Changping Yao
1Division of Neuroscience, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910, USA. May.Lu@na.amedd.army.mil
Abstract:
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.
Insights
This study investigated gene expression changes following ischemic stroke in rats. Key findings reveal distinct temporal patterns of gene upregulation and downregulation, offering new insights into brain injury mechanisms and recovery.
Area of Science:
- Neuroscience
- Molecular Biology
- Genomics
Background:
- Ischemic stroke, such as middle cerebral artery occlusion (MCAo), triggers complex molecular responses in the brain.
- Understanding temporal gene expression changes is crucial for elucidating injury mechanisms and identifying therapeutic targets.
Purpose of the Study:
- To comprehensively analyze temporal gene expression profiles after transient middle cerebral artery occlusion (MCAo) in a rat model.
- To identify novel genes associated with ischemic brain injury and characterize their temporal regulation.
Main Methods:
- DNA microarrays (Affymetrix U34 Rat Neurobiology arrays) were used to analyze gene expression.
- Total RNA was extracted from the injured hemisphere at multiple time points (30 min, 4 hr, 8 hr, 24 hr, 3 days, 7 days) post-MCAo.
- Differential gene expression analysis was performed on 1,322 functional genes.
Main Results:
- 267 genes showed differential expression, with 166 upregulated and 94 downregulated.
- 88 differentially expressed genes were newly identified in relation to ischemic brain injury.
- Early upregulation of immediate early genes, transcription factors, and heat shock proteins was observed, followed by inflammation and apoptosis-related genes.
- Sustained upregulation of neurotrophic growth factors occurred from 24 hr to 7 days post-injury.
- Distinct temporal downregulation patterns were identified for ion channel, neurotransmitter receptor, and synaptic protein genes.
Conclusions:
- Gene expression changes following ischemic stroke exhibit complex temporal dynamics.
- The delayed downregulation of synaptic protein genes suggests a potential role in post-injury recovery.
- This study provides a comprehensive temporal map of gene expression alterations in ischemic brain injury, identifying potential therapeutic targets.
