Inducing stroke in aged, hypertensive, diabetic rats

Abstract

Animal models of ischemic stroke often neglect comorbidities common in patients. This study shows the feasibility of inducing stroke by 2 h of thread occlusion of the middle cerebral artery in aged (56 week old) spontaneously hypertensive rats (SHRs) with both acute (2 weeks) and chronic (36 weeks) diabetes. After modifying the streptozotocin dosing regimen to ensure that old SHRs survived the induction of diabetes, few died after induction of stroke. Induction of stroke is feasible in rats with multiple comorbidities. Inclusion of such comorbid animals may improve translation from the research laboratory to the clinic.

Figure 1

Infarct size, location, and physiologic variables in aged WKY and SHR animals with acute and chronic diabetes. (A) Total infarct volume as a proportion of contralateral hemisphere. Each data point represents an individual animal. (B) Regional involvement in infarction showing contribution of cortical, striatal, and additional subcortical structures. (C) Weight and plasma glucose concentration profile over the chronic diabetic period in SHR. Solid line=weight, dashed line=plasma glucose. circle=WKY nondiabetic; triangle=SHR non-diabetic; diamond=SHR acute diabetic; square=SHR chronic diabetic. (D) Neurologic deficit at 2 and 24 h after MCAo. Scale measures deficit in forelimb flexion, torso twisting, lateral push and mobility. A higher score indicates greater deficit. Solid bars represent deficit at 2 h after MCAo; open bars represent deficit at 24 h after MCAo. All data are presented as mean±s.d. ^*P<0.05 when compared with appropriate nondiabetic WKY control or for specific comparisons indicated.