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A comparison of the early development of ischemic brain damage in normoglycemic and hyperglycemic rats using magnetic
1Marine Biomedical Institute, University of Texas Medical Branch, Galveston 77555-1143, USA.
Abstract:
The early evolution of ischemic brain injury under normoglycemic and streptozotocin-induced hyperglycemic plasma conditions was studied using magnetic resonance imaging (MRI). Male Sprague-Dawley rats were subjected to either permanent middle cerebral artery occlusion (MCAO), or 1-h MCAO followed by reperfusion using the intraluminal suture insertion method. The animals were divided into four groups each with eight rats: normoglycemia with permanent MCAO, normoglycemia with 1-h MCAO, hyperglycemia with permanent MCAO, and hyperglycemia with 1-h MCAO. Diffusion-weighted images (DWIs) and T2-weighted images (T2WIs) were aquired every 1 h from 20 min until 6 h after MCAO, at which time cerebral plasma volume images (PVIs) were acquired. Tissue infarction was determined by triphenyltetrazolium chloride staining at 7 h after MCAO. The ischemic damage, measured as the area of DWI and T2WI hyperintensity and tissue infarction, increased significantly in hyperglycemic rats in both permanent and transient MCAO models. In the permanent MCAO model, the maximal apparent water diffusion coefficient (ADC) decline under either normo- or hyperglycemia was about 40%, but the speed of ADC drop was faster in hyperlgycemic rats than in normoglycemic rats. Reperfusion after 1 h of MCAO in normoglycemic rats partly reversed the decline in ADC, whereas the low ADC area continued to expand after reperfusion in the hyperglycemic group. Between the two hyperglycemic groups with either permanent MCAO or reperfusion, no significant difference was found in the infarct volume measured at 7 h after MCAO. However, reperfusion dramatically increased the extent and accelerated the development rate of vasogenic edema. ADC in the hyperglycemic reperfusion group also dropped to a lower level. A large "no-reflow" zone was found in the ischemic hemisphere in the hyperglycemic reperfusion group. This study provides strong evidence to support that preischemic hyperglycemia exacerbates ischemic damage in both transient and permanent MCAO models and demonstrates, using MRI, that reperfusion under preischemic hyperglycemia accelerates the evolution of early ischemic injury.
Insights
Pre-ischemic hyperglycemia worsens brain injury in both permanent and transient middle cerebral artery occlusion (MCAO) models. MRI shows reperfusion accelerates early ischemic injury evolution under hyperglycemia.
Area of Science:
- Neuroscience
- Medical Imaging
- Biochemistry
Background:
- Ischemic stroke is a leading cause of death and disability.
- Hyperglycemia is a common comorbidity in stroke patients.
- The impact of hyperglycemia on early ischemic brain injury evolution remains incompletely understood.
Purpose of the Study:
- To investigate the early evolution of ischemic brain injury under normoglycemic and hyperglycemic conditions.
- To assess the effects of permanent and transient middle cerebral artery occlusion (MCAO) on brain injury.
- To evaluate the role of reperfusion in hyperglycemic stroke using magnetic resonance imaging (MRI).
Main Methods:
- Male Sprague-Dawley rats were divided into four groups: normoglycemic permanent MCAO, normoglycemic transient MCAO, hyperglycemic permanent MCAO, and hyperglycemic transient MCAO.
- Diffusion-weighted imaging (DWI) and T2-weighted imaging (T2WI) were acquired hourly for 6 hours post-MCAO.
- Triphenyltetrazolium chloride staining was used to determine infarct volume at 7 hours post-MCAO.
Main Results:
- Hyperglycemia significantly exacerbated ischemic damage in both permanent and transient MCAO models.
- In permanent MCAO, the speed of apparent water diffusion coefficient (ADC) drop was faster in hyperglycemic rats.
- Reperfusion in hyperglycemic rats accelerated vasogenic edema and expanded the low ADC area, creating a 'no-reflow' zone.
Conclusions:
- Pre-ischemic hyperglycemia exacerbates ischemic brain damage in both permanent and transient MCAO.
- Reperfusion under hyperglycemic conditions accelerates the evolution of early ischemic injury and edema.
- MRI is a valuable tool for demonstrating the detrimental effects of hyperglycemia on ischemic stroke progression.