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|Title:||ASSESSING COGNITIVE FUNCTION AFTER INTRACEREBRAL HEMORRHAGE IN RATS|
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|Authors/Affiliations:||1 Kristopher Langdon*; 1 Crystal MacLellan; 1 Kayla Churchill; 1 Shirley Granter-Button; 1 Dale Corbett; |
1 Memorial University of Newfoundland, St. John's, NL, Canada
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|Content:||Objectives: Intracerebral hemorrhage (ICH) is a devastating type of stroke that is associated with high mortality and morbidity. Survivors exhibit a range of symptoms including sensory-motor as well as cognitive deficits. It is important that preclinical ICH studies test putative therapies using functional endpoints which are of greatest clinical concern. While sensory-motor tests sensitive to ICH have been identified for several rodent models of ICH, to date no study has attempted to characterize cognitive impairments in rodent models of ICH. Thus, in the present study we sought to assess cognitive function using a battery of tests 1-7 months following ICH.|
Materials and Methods: Twelve male Sprague-Dawley rats weighing ~300g at the time of surgery received, bacterial collagenase (0.12U in 1.0 μL sterile saline) infused into the striatum to create a mild ICH. As a control, an equivalent volume of sterile saline was injected into the striatum of eight additional rats (SHAM). Two days later, functional deficits were assessed using a neurological deficit scale (NDS) and the tape removal test of neglect, which are most sensitive to ICH injury. Because sensory and/or motor deficits may confound cognitive testing, we waited until these symptoms had resolved before testing learning and memory abilities. Cognitive testing was conducted from 1-7 months after ICH and included Spontaneous Alternation, the Morris Water Maze, T-Maze (Win-Shift and Win-Stay paradigms), and the Radial Arm Maze (8 arms baited and 4 arms baited protocols). These tests are routinely used to assess cognitive function after stroke.
Results: ICH produced significant sensory-motor deficits in the NDS and tape removal tests at 2 days, and these deficits had essentially resolved by 1 month (the start of cognitive testing). There were no significant differences between the ICH and SHAM groups in any of the cognitive tests used. Thus, we did not detect learning or memory deficits following ICH.
Conclusion: Persistent cognitive impairments that occur after ICH in humans were not observed in this study. Animal models that better mimic clinical ICH (both motor and cognitive deficits) must be developed. Potential avenues to improve animal models of ICH include, increasing the severity of ICH lesion or injuring other functional subdivisions (eg. a more medial injury) within the striatum that would be more likely to lead to profound cognitive deficits. These possibilities need to be further explored in future studies in order to develop effective neuroprotective and rehabilitative strategies for ICH in the clinic.
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