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Effects of hyperglycemia on ischemic brain damage, local cerebral blood flow and ischemic cerebral edema
1Department of Neurosurgery, Asahikawa Medical College, Japan.
Abstract:
The effects of hyperglycemia on ischemic brain damage, local cerebral blood flow (LCBF), and ischemic cerebral edema were studied in a rat model of transient middle cerebral artery (MCA) occlusion with a microclip. Hyperglycemia was induced by intraperitoneal injection of 50% glucose, and same volume of 50% D-mannitol or physiological saline were injected in the controls. LCBF was measured by the quantitative autoradiogram using 14C-iodoantipyrine at 2 hours after MCA occlusion and 2 hours after reperfusion. Cerebrovascular permeability was measured by same technique using 14C-alpha-aminoisobutyric acid (AIB) at 2 hours after reperfusion following 2 hours ischemia. Specific gravity of the brain, determined by the gradient column, was used to study the topographic changes of brain water content at 2 hours after MCA occlusion and 2 hours after reperfusion. Some rats were prepared for neuropathological observation 72 hours after reperfusion. Histological study 72 hours after restoration of CBF following 2 hours MCA occlusion revealed ischemia neuronal cell damage to be more extensive in hyperglycemic rats than in normoglycemic rats. LCBF in the ischemic focus decreased significantly in hyperglycemic rats compared with the controls at 2 hours after MCA occlusion. Furthermore, the reduction of LCBF was observed also in the contralateral non-ischemic side. At 2 hours after reperfusion, in hyperglycemic rats, hyperemia up to 121-156% of the contralateral LCBF was observed within the previously ischemic area, along with a zone of reduced CBF in the surrounding area. At 2 hours after MCA occlusion, the decrease of specific gravity of the ischemic brain, in hyperglycemic rats, was significant compared with the control, and these decreases became more prominent in the entire territory of the MCA at 2 hours after reperfusion. Furthermore, 14C-AIB autoradiogram disclosed the prominent and wide leakage of the tracer within the previous ischemic focus of MCA occlusion. In contrast, in normoglycemic rats, ischemic brain edema showed a reducing trend after reperfusion, and no demonstrable changes of cerebrovascular permeability were disclosed on autoradiograms. These findings suggest that the enhancing mechanisms of hyperglycemia for ischemic brain damage are severely reduced CBF during ischemia and postischemic vasogenic edema.
Insights
Hyperglycemia worsens ischemic brain damage by reducing blood flow during stroke and increasing brain swelling after reperfusion. This study highlights the detrimental effects of high blood sugar on stroke outcomes in rats.
Area of Science:
- Neuroscience
- Pathophysiology
- Cerebrovascular Disease
Background:
- Hyperglycemia is common in acute ischemic stroke.
- Its precise impact on ischemic brain damage, cerebral blood flow, and edema remains under investigation.
Purpose of the Study:
- To investigate the effects of hyperglycemia on ischemic brain damage, local cerebral blood flow (LCBF), and ischemic cerebral edema in a rat model.
- To elucidate the mechanisms by which hyperglycemia exacerbates ischemic brain injury.
Main Methods:
- Transient middle cerebral artery (MCA) occlusion model in rats.
- Induction of hyperglycemia using glucose injection; controls received mannitol or saline.
- Measurement of LCBF using quantitative autoradiography (14C-iodoantipyrine).
- Assessment of cerebrovascular permeability using 14C-alpha-aminoisobutyric acid (AIB) autoradiography.
- Determination of brain water content via specific gravity measurements.
- Neuropathological evaluation 72 hours post-reperfusion.
Main Results:
- Hyperglycemic rats exhibited more extensive neuronal cell damage compared to normoglycemic controls.
- LCBF was significantly reduced in the ischemic focus and contralateral hemisphere in hyperglycemic rats during ischemia.
- Post-reperfusion, hyperglycemic rats showed hyperemia in the ischemic area but reduced blood flow in surrounding regions.
- Significant decrease in brain specific gravity (indicating edema) and prominent tracer leakage (increased permeability) were observed in hyperglycemic rats.
- Normoglycemic rats showed a trend towards reduced edema post-reperfusion with no significant changes in cerebrovascular permeability.
Conclusions:
- Hyperglycemia exacerbates ischemic brain damage through reduced cerebral blood flow during ischemia and increased post-ischemic vasogenic edema.
- These findings underscore the importance of glycemic control in managing acute ischemic stroke.