A better understanding of the developing neonatal respiratory system has resulted in a better management of the premature infant respiratory problems. Unfortunately, a similar statement cannot be made about the management of neonatal intracerebral damage, or of its devastating clinical sequelae. An obvious reason for this discrepancy lies in the fact that our understanding of the neonatal brain structure and vasculature is inadequate, and in some areas (vulnerability of matrix capillaries) lacking. We all are painfully aware that the number of children with """"""""Minimal Brain Damage: is increasing, as more and more premature infants survive because of improvements in the management of their respiratory problems.
The aims of this research are; a. study the structural organization of the developing (normal and abnormal) cerebellar and cerebral cortices and their vasculature, b, acquire a better understanding of the neonatal brain, c. utilize that knowledge to improve the management of neonatal intracerebral damage. The investigative tools are; the Golgi method, computer enhance neuronal morphometry, electron microscopy, and immunohistochemistry. The proposed studies are; A. Neurogenesis of Golgi cells of the developing neonatal cerebellum. B. Structural organization of marginal heterotopias of the cerebral cortex. Cortical heterotopias have been described in epilepsy, dyslexia, cerebral palsy, and mental retardation, however their structure remains poorly understood. C. Study cerebral cortex (frontal, motor, Broca's auditory and visual areas) Down's syndrome. D. Study neonatal development and distribution of short circuit cortical neurons. E. Continuation 'maps' reconstructions neonatal brain at various ages to be used as reference data. F. Continuation of neonatal brains collection for future studies. G. Preliminary light and EM immunohistochemical experimental studies of the embryonic vascularization of the cerebral cortex of 11-12 day old mouse embryos.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS022897-04
Application #
3405680
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1986-02-01
Project End
1996-01-31
Budget Start
1989-02-01
Budget End
1990-01-31
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Dartmouth College
Department
Type
Schools of Medicine
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755
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Marin-Padilla, M (2000) Perinatal brain damage, cortical reorganization (acquired cortical dysplasias), and epilepsy. Adv Neurol 84:153-72
Marin-Padilla, M (1999) Developmental neuropathology and impact of perinatal brain damage. III: gray matter lesions of the neocortex. J Neuropathol Exp Neurol 58:407-29
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Marin-Padilla, M (1998) Cajal-Retzius cells and the development of the neocortex. Trends Neurosci 21:64-71
Marin-Padilla, M (1997) Developmental neuropathology and impact of perinatal brain damage. II: white matter lesions of the neocortex. J Neuropathol Exp Neurol 56:219-35
Marin-Padilla, M (1997) [Pathology and pathogenesis of secondary epilepsy to hypoxic-ischemic encephalopathies] Rev Neurol 25:673-82
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Wang, Q; Stacy, T; Binder, M et al. (1996) Disruption of the Cbfa2 gene causes necrosis and hemorrhaging in the central nervous system and blocks definitive hematopoiesis. Proc Natl Acad Sci U S A 93:3444-9

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