The effects of environment on enhancing functional plasticity following cerebral ischemia.

This dissertation examined the usefulness of an enriched environment in the recovery of learning deficits resulting from cerebral ischemia. Initially, it was necessary to create an animal model of ischemia consistent with that seen in human survivors of traumatic brain injury and cardiac arrest. Thus, the first study compared two short durations of ischemia. It was hypothesized that duration of ischemia is related to extent of hippocampal damage and degree of spatial learning deficit. Adult female rats received either 5 or 10 min ischemia or sham surgery. After recovery, animals were tested for 6 days on a spatial learning task. Results showed that animals with 10 min ischemia demonstrated persistent learning impairments across the test days as compared to the 5 min ischemic group. Analysis of cell loss showed confined damage to hippocampal subfields. Five min ischemia produced moderate damage in hippocampal CA1 and CA3 and minimal damage in CA2. With 10 min ischemia increased cell loss was seen in all subfields especially in CA1. Furthermore, the degree of CA1 cell loss accounted for 45% of the variance in behavioral performance. Using the 10 minute ischemic model, the second study examined the: (1) effects of early exposure to an enriched environment following ischemia on functional plasticity; (2) relationship between morphological and behavioral plasticity (functional plasticity); and (3) influence of exploration on functional plasticity during environmental enrichment. Adult female rats were divided into: ischemia and control groups. Each group was further randomized to either standard (SC) or enriched (EC) conditions. After four days of exposure to differential environments, rats were tested for spatial learning performance. Behavioral results showed that ischemic rats exposed to EC performed as well as controls; while those exposed to SC showed significant learning impairment. No differences in exploratory behaviors were seen across groups. Histology revealed that control and ischemic rats exposed to EC have increased total dendritic length, increased number of dendritic segments, and greater dendritic spine density as compared to rats housed in SC. Moreover, a significant positive relationship was revealed between spatial learning performance and spine density. It is concluded that environmental enrichment enhances functional plasticity following cerebral ischemia.PhDBiological SciencesCognitive psychologyHealth and Environmental SciencesNeurosciencesNursingPsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/130205/2/9721950.pd