Introduction: Stroke remains a colossal problem worldwide. Despite the advances in medical technology only 4% of strokes are treated, making it the fourth leading cause of death. Several round table discussions have been held with industry leaders and consistently it has been recommended that large animal stroke studies are needed to evaluate new treatments.
Methods: Twenty adult male Beagles where used in our study. We compared endovascular, combined endovascular/surgical and purely surgical methods for developing our model. A surgical approach modified from Yanaka et al, 1996 was used. Briefly, a pterional craniotomy is performed with drilling of the temporal floor, minimizing retraction on the temporal lobe. The azygous ACA is identified and clipped. The MCA is then identified and coagulated and cut distal to the lenticulostriate vessels. Using indocyanine green we then identify collateral blood flow to the distal MCA which is then occluded through vessel coagulation. After one hour the aneurysm clip is removed and the animals recovered. Neurological examination is then performed based on a modified protocol from Boulus et al.
Results: Our current approach has now been validated in our last 6 animals with no mortality. Stroke is seen on MRI at 24 hours with an average volume of 1469.5 ± 173.62 mm3. This remains stable at one week. The average stroke volume determined histologically at one month is 1763.1 ± 16.8 mm3. Neurological exam consistently demonstrates left sided weakness, neglect, and circling, falling to the left and unstable gait. While weakness improves in some animals the remainder of deficits are persistent in all animals. Average neurological score at 24 hours and one week are 25±3.6
and 18.75±7.9 respectively.
Conclusions: We have developed a highly consistent and predictable large animal canine stroke model with very low mortality.
Patient Care: Despite advances in acute therapy only 5% of patients are ever treated and only a portion successfully. We have developed a unique canine surgical stroke model with the applicability to investigate direct neuronal reprogramming. Direct reprogramming is distinct because cell transformation can occur without a pluripotent intermediate state. This leads to the novel idea that endogenous cells within the brain could potentially be reprogrammed in vivo, avoiding the need for cell transplantation and potentially exploiting environmental influences for phenotypic differentiation, migration and
integration.
Learning Objectives: By the conclusion of this session participants should be able to be familiarized with the different large animal stroke models. 2 Discuss in small groups current basic science research for CNS cell regeneration and cell reprograming. 3) Identify an effective treatment for stroke