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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS025780-03
Application #
3411225
Study Section
Neurology A Study Section (NEUA)
Project Start
1988-02-01
Project End
1992-01-31
Budget Start
1990-02-01
Budget End
1992-01-31
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Other Domestic Higher Education
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Villablanca, Jaime R (2010) Why do we have a caudate nucleus? Acta Neurobiol Exp (Wars) 70:95-105
Loopuijt, L D; Villablanca, J R; Sharifi, P (2001) Soma size of substantia nigra neurons increases after a prenatal neocortical lesion in cats. Brain Res Dev Brain Res 130:143-7
Villablanca, J R; Hovda, D A (2000) Developmental neuroplasticity in a model of cerebral hemispherectomy and stroke. Neuroscience 95:625-37
Villablanca, J R; Schmanke, T D; Crutcher, H A et al. (2000) The growth of the feline brain from fetal into adult life. II. A morphometric study of subcortical nuclei. Brain Res Dev Brain Res 122:21-33
Villablanca, J R; Schmanke, T D; Lekht, V et al. (2000) The growth of the feline brain from late fetal into adult life. I. A morphometric study of the neocortex and white matter. Brain Res Dev Brain Res 122:20-Nov
Villablanca, J R; Schmanke, T D; Hovda, D A (1999) Effects of a restricted unilateral neocortical lesion upon cerebral glucose and oxidative metabolisms in fetal and neonatal cats. Brain Res Dev Brain Res 117:1-13
Villablanca, J R; Carlson-Kuhta, P; Schmanke, T D et al. (1998) A critical maturational period of reduced brain vulnerability to developmental injury. I. Behavioral studies in cats. Brain Res Dev Brain Res 105:309-24
Schmanke, T D; Villablanca, J R; Lekht, V et al. (1998) A critical period for reduced brain vulnerability to developmental injury. II. Volumetric study of the neocortex and thalamus in cats. Brain Res Dev Brain Res 105:325-37
Loopuijt, L D; Villablanca, J R; Hovda, D A et al. (1997) The effect of neocortical lesions on the number of cells in neonatal or adult feline caudate nucleus: comparison to fetal lesions. Neuroscience 77:403-18
Adelson, P D; Hovda, D A; Villablanca, J R et al. (1995) Development of a crossed corticotectal pathway following cerebral hemispherectomy in cats: a quantitative study of the projecting neurons. Brain Res Dev Brain Res 86:81-93

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