Exp Neurobiol 2007; 16(1): 1-8

Published online July 1, 2007

© The Korean Society for Brain and Neural Sciences

Development of Animal Model for Cerebral Palsy Based on Impairment of Neonatal Gamma-aminobutyric Acid (GABA)

Albert K. Song1,3, Nami Palikhe1, Gun Tae Kim1, Jing Li4, Jong Doo Lee2, Kee Won Kim4 and Dong Goo Kim1*

Departments of 1Pharmacology and 2Diagnostic Radiology, Brain Korea 21 Project for Medical Sciences, Brain Research Institute, Yonsei University College of Medicine, Seoul 120-752, Korea, 3Johns Hopkins University, Zanvyl Krieger School of Arts and Science, Baltimore, MD, USA, 4Department of Pharmacology, Institute for Medical Science, Chonbuk National University Medical School, Jeonju 561-180, Korea

Correspondence to: *To whom correspondence should be addressed.
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In spastic diplegic cerebral palsy (CP) patients, we found increased 18F-fluoroflumazenil binding in the bilateral precentral gyri, regardless of the presence of periventricular leukomalacia (PVL) in a positron emission tomography (PET) study. In this study, we aimed to develop an animal model that would corroborate the findings above by impairing GABA function of neonatal rats during development. Sprague-Dawley rat pups were daily injected with GABAergic drugs, and exposed to anoxic environment for 25 minutes using 100% N2 gas on postnatal day (PND) 2, 3, and 4. GABAergic drugs we used were muscimol (0.1 mg/kg, s.c.), and biccuculine (1 mg/kg, s.c.), a GABAA receptor agonist and an antagonist respectively, and diazepam (1 mg/kg, s.c.), a benzodiazepine receptor agonist. Developmental and neurological tests, conducted on PND 16, 23, and 30, did not yield any significant differences. However, an impaired motor coordination was observed in the Anoxia-Muscimol group which showed decreased [3H]flumazenil binding and an increased dopamine turnover in the cerebral cortex. Considering data of cerebral palsy patients, the present results suggest that the pathophysiological process of cerebral palsy occur in the early prenatal period, not in the perinatal period.

Keywords: cerebral palsy, gamma-aminobutyric acid, animal model, developmental disability