Using a sensorimotor systems, neonatal-adult cat lesion model developed in our lab., we propose testing 3 intervention procedures which may enhance recovery of function and anatomical reorganization after brain injury. Five to 15 day old kittens and adult cats receive ablation of one cerebral hemisphere (modeling extensive capsular stroke and therapeutic hemispherectomy) and are divided into 3 groups. Group A animals are exercised and motor-trained extensively. Group B cats receive monosialoganglioside. Group C cats are given neuronal growth factors. Starting 5 months after brain damage, animals are assessed using an extensive battery of neurological and behavioral tests. In addition, developmental disability-type impairments are followed in kittens. At the end, animals' brain are examined to measure: a) extent of collateral sprouting of axon terminals of pathways from the motor cortex of the intact hemisphere which reinnervate deafferented targes (tritiated amino acids autoradiography); b) amount of retrograde degeneration and atrophy in thalamic- brain stem nuclei (computerized morphometrics); c) changes in metabolic activity in brain areas where we showed (or suspect) postinjury functional anatomical reorganization (cytochrome oxidase histochemistry). For all above measures groups are compared to untreated neonatal and adult hemispherectomized cats and to """"""""saline"""""""" controls. In previous work or methods differentiated impressive behavioral recovery coupled with robust novel axonal growth and reduced neuronal degeneration, in neonatal-lesioned, versus less recovery coupled with reduced neural growth and increased degeneration, in adult lesioned cats. Because we provide quantitative analyses of classical sensorimotor systems in an advanced mammal with an extensive behavioral repertoire and a perinatal timecourse of brain development similar to man, our results will have broad implications for both adult and pediatric neurology. In particular, these studies are important because: (1) there is no anatomical validation of exercise and training in promoting true recovery after gross or subtle (mental retardation, developmental disabilities) brain damage and controlled behavioral studies are meager; (2) although neuronal-promoting roles of gangliosides and nerve growth factors are well established, proof of their efficacy to restore brain damage in a higher mammal, in vivo model is lacking; and (3) the proposed treatments do not induce side effects such that the possible future applications appear highly desirable.
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