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|Title:||BEHAVIOURAL OUTCOME FOLLOWING THE INTRALUMINAL MODEL OF SUBARACHNOID HEMORRHAGE IN RATS.|
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|Authors/Affiliations:||1 Gergely Silasi*; 1 Frederick Colbourne; |
1 University of Alberta, Edmonton, AB, Canada
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|Content:||Objectives: Subarachnoid hemorrhage (SAH) is a severe form of stroke that is caused by the bursting of a blood vessel on the surface of the brain, thus resulting in the accumulation of blood in the subarachnoid space. The intraluminal suture model of SAH encompasses many of the clinically relevant features of this form of stroke, however long-term behavioural outcome has not been described in this model. Given that SAH in patients results in enduring behavioural deficits it would be important to determine whether the intraluminal suture model is appropriate for testing the efficacy of potential treatments for SAH. The aim of the current study was to characterize the long-term behavioural outcome following the intraluminal perforation model of SAH.|
Materials and Methods: Adult rats were trained on a battery of motor tasks (horizontal ladder, tapered beam, Schallert cylinder) prior to receiving an SAH injury. To induce the SAH a sharpened nylon suture was advanced into the cranium through the internal carotid artery (ICA) and the vessel wall at the point of the ICA bifurcation was perforated. The rats were then evaluated on the above motor tasks for 3 weeks after the injury. To determine if SAH resulted in any cognitive impairments the rats were subsequently tested on a moving platform version of the Morris Water Task (MWT), allowing us to asses both 24 hr retention of place learning as well as the ability to develop efficient search strategies. The rats were sacrificed at about 6 weeks post-injury and cressyl violet stained sections were used to detect areas of necrosis and to perform cortical thickness measurements.
Results: The mortality rate for the current study was 28% and the cause of death in all of these cases was determined to be cerebellar herniation. At the completion of the motor testing (3 weeks post-injury) SAH rats did not have any lasting impairments on the tapered beam or the horizontal ladder tasks. Similarly, the SAH rats showed symmetrical use of their forepaws when exploring the Schallert cylinder, indicating that SAH did not induce any lasting motor impairments. In the MWT, however, SAH rats took significantly longer (25% increase from control) to find the platform on days when it was moved to a novel location within the pool, indicating that they failed to develop efficient searching strategies to meet the demands of the task. Histologically, we confirmed previous reports indicating that there is significant variability in hemorrhage severity in this model, however we did not find any significant group differences on cortical thickness, and only a small number of brains had frank tissue loss at the site of the hemorrhage.
Conclusion: Based on these findings it can be concluded that while the intraluminal model of SAH may be optimal for investigating the efficacy of treatments that could potentially reduce the volume of the initial bleed, treatment effects on functional outcome would be difficult to determine.
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