title: Consequences of reduced cerebral blood flow in brain development. II. Retardation of neurological outcome and phosphorus metabolism.
abstract: We investigated the temporal relationship of the emergence of biochemical abnormalities to the development of behavioral dysfunction to identify the central factors of ischemic neurological disorders in developing brains. To induce early ischemia, bilateral carotid artery occlusion (BCAO) was surgically performed on 21 cats at the second week of age. BCAO produces histopathological damage, including neuronal loss and thinning of white matter. 31P magnetic resonance spectroscopy was used to monitor brain oxidative metabolism, neuronal membrane growth, and myelination of the prefrontal cortex in the first 3 months. Neurological development was monitored by conducting 25 tests of reflex, motor, sensory, and integrated behavioral function. At 1 month, phosphodiester (PDE) levels, a component of membranes and myelin, were low in animals showing complete ligation. At 2 months, the growth of PDE was low (1/4 to 1/2 of normal) in BCAO animals, whereas normal animals demonstrated a 23% increase. Phosphocreatine (PCr) levels, indicated by PCr/ATP and PCr/inorganic phosphate ratios, were retarded at 2 months in completely ligated animals (1/4 of normal). Neurologically, the completely ligated animals showed retardation of general development. The retardation was most pronounced for integrative functions, including visual function, and became more pronounced later in development. The time course of emergence of the retardation generally coincided with emergence of abnormalities in phosphorous compounds. The simultaneous occurrence of several biochemical and functional abnormalities in development following early ischemic insult suggests a causal relationship between membrane and mitochondrial development and neurological function.
authors.affiliation: Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia 19104.
authors.forename: S
authors.initials: S
authors.lastname: Nioka
authors.forename: A
authors.initials: A
authors.lastname: Zaman
authors.forename: D
authors.initials: D
authors.lastname: Nagy
authors.forename: B
authors.initials: B
authors.lastname: Miller
authors.forename: B L
authors.initials: BL
authors.lastname: Finlay
authors.forename: B
authors.initials: B
authors.lastname: Chance
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000375:Aging / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002339:Carotid Arteries; D002415:Cats; D002560:Cerebrovascular Circulation; D004734:Energy Metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D009043:Motor Activity; D009046:Motor Neurons / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D010758:Phosphorus; D012018:Reflex
chemical_list: D010710:Phosphates; D010725:Phosphocreatine; D010758:Phosphorus; D000255:Adenosine Triphosphate