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Locomotor and passive avoidance deficits following occlusion of the middle cerebral artery
C V Borlongan1, D W Cahill, P R Sanberg
1Department of Surgery, University of South Florida College of Medicine, Tampa 33612, USA.
Abstract:
The characterization of sensory, motor and cognitive dysfunctions following occlusion of the middle cerebral artery (MCA) is prerequisite to investigations of treatment intervention in animal models of ischemia. Different strategies are used to induce ischemia, but the focal, transient occlusion of the MCA has been reported to result in neuropathology most similar to that seen in clinical cerebral ischemia. If the MCA occlusion technique results in a stroke animal model, then the behavioral impairments inherent in stroke should be manifested in this model. The present study provides a further characterization of behavioral alterations associated with MCA occlusion. Sprague-Dawley rats underwent temporal occlusion of the right MCA, and at 1 mo and 2 mo postischemia, were subsequently tested in passive avoidance behavior, motor coordination, asymmetrical motor behavior, neurological functioning, nocturnal spontaneous and amphetamine-induced locomotor activity, and haloperidol-induced catalepsy. Results revealed that ischemic rats showed long-term impairments in sensory, motor and cognitive functions. The discrepancy with other studies reporting temporal MCA-induced behavioral deficits may be due to techniques used to induce ischemia and consequent CNS damage, differences in time period of testing (i.e., immediate vs. later postischemia, nighttime vs. daytime), number of test-retests over the course of the experiment, and age of the animals. The mechanism involved in the MCA-induced behavioral changes may be represented by loss of dopamine receptors on striatal neurons. Histological analysis revealed damage limited to the lateral aspect of the striatum. These behavioral and anatomical data support MCA occlusion as a model of ischemia, and elucidate important factors that should be controlled for in characterizing the MCA-induced neuropathological alterations.
Insights
Middle cerebral artery (MCA) occlusion in rats causes long-term sensory, motor, and cognitive deficits, validating its use as an ischemia model. Careful control of experimental factors is crucial for accurate characterization of stroke-induced changes.
Area of Science:
- Neuroscience
- Neurology
- Animal Models of Disease
Background:
- Characterizing sensory, motor, and cognitive dysfunctions after middle cerebral artery (MCA) occlusion is essential for developing treatments in ischemia animal models.
- Focal, transient MCA occlusion produces neuropathology closely resembling human cerebral ischemia.
- Stroke animal models should manifest behavioral impairments consistent with stroke.
Purpose of the Study:
- To further characterize the behavioral alterations associated with MCA occlusion in a rat model.
- To establish the validity of MCA occlusion as a model for studying cerebral ischemia and its consequences.
Main Methods:
- Sprague-Dawley rats underwent temporal occlusion of the right MCA.
- Postischemia testing at 1 and 2 months included passive avoidance, motor coordination, asymmetry, neurological function, locomotor activity (spontaneous and amphetamine-induced), and haloperidol-induced catalepsy.
- Histological analysis assessed the extent of brain damage.
Main Results:
- Ischemic rats exhibited persistent long-term impairments in sensory, motor, and cognitive functions.
- Histological analysis confirmed damage localized to the lateral striatum.
- Behavioral and anatomical data support MCA occlusion as a relevant ischemia model.
Conclusions:
- MCA occlusion in rats results in long-term sensory, motor, and cognitive deficits, supporting its use as an animal model of cerebral ischemia.
- Discrepancies in findings across studies may stem from variations in ischemia induction techniques, testing parameters, and animal age.
- Potential mechanisms include dopamine receptor loss in striatal neurons, with damage confined to the lateral striatum.