Regional expression of heat shock protein-70 mRNA and c-fos mRNA following focal ischemia in rat brain
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F A Welsh1, D J Moyer, V A Harris
1Division of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia.
Abstract:
In situ hybridization was used to estimate regional levels of heat shock protein-70 (HSP-70) mRNA and c-fos mRNA in two related models of focal cerebral ischemia. In the first model, permanent occlusion of the distal middle cerebral artery (MCA) alone caused a patchy increase in HSP-70 mRNA by 1 h in the central zone of the MCA territory of the ipsilateral neocortex. Tissue levels of HSP-70 mRNA continued to increase for several hours and remained elevated at 24 h. In contrast to the focal expression of HSP-70, c-fos mRNA was increased throughout the ipsilateral cerebral cortex by 15 min and remained elevated for least 3 h. The wide distribution of c-fos expression suggests it may have been caused by spreading depression. In the second model, severe focal ischemia was produced with a combination of transient (1-h) bilateral carotid artery occlusion and permanent MCA occlusion. Combined occlusion for 1 h without reperfusion caused expression of HSP-70 mRNA only in regions adjacent to the central zone of the MCA territory of the neocortex. However, reperfusion of the carotids for 2 h generated intense expression of HSP-70 mRNA throughout most of the ipsilateral cerebral cortex, white matter, striatum, and hippocampus. The wide-spread increase in HSP-70 mRNA suggests that reperfusion triggered expression in all previously ischemic regions. However, at 24 h of reperfusion, increased levels of HSP-70 mRNA were restricted primarily to the ischemic core of the neocortex. These results suggest that expression of HSP-70 mRNA is prolonged in regions undergoing injury, but is transient in surrounding regions that recover.
Insights
Heat shock protein-70 (HSP-70) mRNA levels indicate brain injury during focal cerebral ischemia. HSP-70 mRNA expression is prolonged in injured brain regions, suggesting its utility in assessing ischemic damage.
Area of Science:
- Neuroscience
- Molecular Biology
- Pathology
Background:
- Focal cerebral ischemia, a leading cause of stroke, involves restricted blood flow to the brain.
- Heat shock proteins (HSP-70) are cellular stress markers, and their expression patterns in ischemia are not fully understood.
- c-fos mRNA is an immediate-early gene often induced by neuronal activity and stress.
Purpose of the Study:
- To investigate the regional expression patterns of heat shock protein-70 (HSP-70) mRNA and c-fos mRNA in response to focal cerebral ischemia.
- To differentiate the temporal and spatial dynamics of HSP-70 and c-fos mRNA expression in ischemic brain tissue.
Main Methods:
- In situ hybridization was employed to quantify HSP-70 mRNA and c-fos mRNA levels in two distinct models of focal cerebral ischemia.
- Model 1: Permanent middle cerebral artery (MCA) occlusion.
- Model 2: Transient bilateral carotid artery occlusion combined with permanent MCA occlusion, with and without reperfusion.
Main Results:
- Permanent MCA occlusion induced focal HSP-70 mRNA expression in the neocortex, increasing over hours and remaining elevated at 24h.
- c-fos mRNA showed widespread, transient expression throughout the ipsilateral cortex within 15 minutes, suggesting induction by spreading depression.
- Reperfusion following combined occlusion led to widespread HSP-70 mRNA expression, which later became restricted to the ischemic core at 24h.
Conclusions:
- HSP-70 mRNA expression is prolonged in brain regions undergoing sustained injury during focal cerebral ischemia.
- HSP-70 mRNA expression is transient in surrounding brain regions that recover after ischemic insult.
- The distinct expression patterns of HSP-70 and c-fos mRNA provide insights into the cellular responses to ischemic injury and reperfusion.