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(Stroke. 1995;26:2338-2346.)
© 1995 American Heart Association, Inc.

Articles

Nonocclusive Common Carotid Artery Thrombosis in the Rat Results in Reversible Sensorimotor and Cognitive Behavioral Deficits

Nancy E. Alexis, MS; W. Dalton Dietrich, PhD; Edward J. Green, PhD; Ricardo Prado, MD Brant D. Watson, PhD

From the Cerebral Vascular Disease Research Center, Department of Neurology, University of Miami School of Medicine, and Department of Psychology (E.J.G.), University of Miami, Coral Gables, Fla.

Background and Purpose Microemboli released during transient ischemic attack, stroke, and cardiac surgery are thought to cause a variety of functional deficits in humans. The purpose of this study was to characterize the type and extent of neurobehavioral deficits present after photochemically induced common carotid artery thrombosis (CCAT), a thromboembolic model of stroke in the rat that results in a platelet emboli shower.

Methods Thirty-two male Wistar rats were assigned to four groups. Groups 1 (n=8) and 3 (n=8) were long-term (6-week survival) and short-term (2-week survival) experimental groups subjected to right CCAT with the use of the photochemical technique. Groups 2 (n=8) and 4 (n=8) served as sham-operated controls for each experimental group. A battery of behavioral tests was applied daily beginning 24 hours after thrombosis; this consisted of elicited forelimb placing, postural reflex, beam balance, beam walking, and open field activity. Cognitive testing with a water maze task was performed on post-CCAT days 30 to 33 for groups 1 and 2 and on post-CCAT day 2 for groups 3 and 4. Ten-micrometer coronal brain sections were stained with hematoxylin and eosin, and infarct location and frequency were determined.

Results Significant sensorimotor deficits were observed, which recovered within 2 weeks after CCAT. The data that follow are derived by combining the two experimental groups and comparing these with the two sham groups. The following tests showed significant effects after CCAT: contralateral elicited forelimb placing, ipsilateral elicited forelimb placing, beam balance, and beam walking score. Cognitive dysfunction was seen acutely (group 3 animals) at 2 days after CCAT; Morris water maze length and latency to target were significantly greater in the experimental group. No deficits were seen in postural reflex, open field activity, or delayed cognitive testing. Histopathological assessment revealed small infarcts in 11 of 16 thrombosed rats. However, a strong relationship between neurobehavioral deficits and infarct location was not consistently demonstrated.

Conclusions CCAT produces consistent sensorimotor and cognitive behavioral deficits that recover within 2 weeks of injury. Behavioral outcome was not necessarily associated with overt histopathological damage, suggesting that reversible injury mechanisms, both vascular and neuronal, may be partly responsible for the temporary loss of function. These data strengthen the role of CCAT as a clinically relevant model of thromboembolic stroke.

Key Words: behavior, animal • cerebral ischemia • cognition • stroke • rats

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