Abstract TMP36: Persistent Stroke-induced Sensory, Motor And Cognitive Deficits Involve Long-term Myelin Loss In Major Fiber Tracts

Abstract

Objectives: Persistent neurobehavioral deficits and brain changes need validation for future brain restoration research. Here neurological and brain changes were determined post-stroke for this purpose. Methods: Two hr middle cerebral artery occlusion (tMCAO) or sham (Sham) surgery was performed in male SD rats. Measurements made over 10 weeks included: (1) sensory, motor, beam balance, hindlimb and forepaw behaviors, and (2) complex active place avoidance learning (APA) and simple passive avoidance retention (PA). Electroretinogram (ERG) was measured at term. Measurements of hemispheric loss (infarction), hippocampus CA1 neuronal loss and myelin (Luxol Fast Blue) staining in several fiber tracts were made. Results: Compared to Sham, tMCAO produced significant but acute deficits in forelimb foot fault for only 1 day (max 2144 ± 556 % change, p<0.01) and forelimb cylinder placement for only 2 weeks (max 822 ± 215 % change, p<0.01). Persistent deficits for the 10 week period were exhibited for motor, sensory and beam balance performance and for hindlimb placement (all > 20-fold, p<0.001). Motor behavior and beam balance deficits, although persistent, did decrease 30-40 % over time. tMCAO produced significant, cognitive deficits in APA learning but did not affect PA retention. The impaired APA learning (max 604 ± 83 % change, p<0.001) was prolonged, and in fact exhibited progressive worsening (> 2-fold) over time, thus being most sensitive to brain injury. ERG indicated no difference in visual function. Percent hemispheric loss measured at term was cross-validated by 2 different staining methods (33 ± 4 % for H&E and 34 ± 4 % for TTC). No hippocampus neuronal loss occurred. Fiber tract myelin loss was significant (> 2-fold, P<0.01) in the external capsule and striatum but not in the corpus callosum or anterior commissure. Conclusions: Persistent deficits were identified for neurobehavioral end points for use in future restoration research. Fiber myelin loss in the external capsule and striatum contribute to long term deficits, apparently especially important for cognitive control necessary in complex learning. Investigation of myelin protection/regrowth mediated by oligodendrocytes, and perhaps other cells, will be essential to future stroke research.