Abstract T P208: Diabetes Exacerbates Neurovascular And White Matter Disruptions in Older Rats After Stroke
Background and Purpose: Diabetes mellitus (DM) is a common metabolic disease in the aged population, which leads to an increase of stroke incidence, poor stroke outcome, and slower neurological recovery. A better understanding of the pathological cascades of brain injury in the aged DM population is of major clinical importance for stroke management. The present study was designed to characterize the behavioral and pathological changes in older DM rats after embolic stroke.
Methods: Male Wistar rats at age of 13 months were subjected to intraperitoneal nicotinamide (NTM, 210mg/kg) and streptozotocin (STZ, 60mg/kg) injection (n=19). Rats were subjected to embolic middle cerebral artery occlusion (MCAo) 30d after induction of DM (n=10). Aged matched normal rats (n=9) and ischemic rats (n=11) without induction of DM were used as controls.
Results: Rats subjected to STZ-NTM administration exhibited persistent hyperglycemia and reduction of insulin producing pancreatic β-cells, and have clinical manifestations of type 2 DM (T2DM). These rats exhibited substantial spatial learning deficits measured by the Morris water maze (39±3 vs 50±4% of time spent in the correct quadrant in age matched non-DM rats, p<0.05) 65d after induction of DM. Histological analysis revealed that there was patchy vascular and parenchymal fibrin deposition mainly in the hippocampus and white matter, which were associated with significant (p<0.05) reductions in neurofilament positive axonal density (14±3 vs 23±4% in non-DM rats) and myelinating oligodendrocytes (78±11 vs 98±13/mm2). Stroke in DM rats exacerbated vascular and parenchymal fibrin deposition (32±8 vs 17±6 mm2 in non-DM ischemic rats), decreased axonal density (9±2 vs 17±4%) and dendritic spines (10±4 vs 19±5/μm), and increased loss of oligodendrocytes (47±12 vs 73±14/mm2), which were associated with spatial learning and neurological deficits 35d after stroke onset, although the primary infarct volumes within the MCA territory were not different between groups.
Conclusions: T2DM exacerbates neurovascular and white matter damage, leading to neurological deficits in older rats, which closely resembles pathological symptoms observed in stroke patients with T2DM.
Author Disclosures: L. Zhang: None. M. Chopp: None. Y. Zhang: None. Y. xiong: None. Z. Zhang: None.
- © 2014 by American Heart Association, Inc.