Early appearance of functional deficits after neonatal excitotoxic and hypoxic-ischemic injury: fragile recovery after development and role of the NMDA receptor.

Abstract

We sought to determine whether neonatal rats that sustain unilateral cerebral hypoxic-ischemic or excitotoxic insults (1) manifest contralateral sensorimotor deficits during development or in adulthood and (2) recover from those deficits. Seven-day-old (P7) rats received a right intrastriatal injection of the glutamate analog N-methyl-D-aspartate (NMDA). Unilateral hypoxia-ischemia (HI) was induced by right carotid ligation followed by 1.5 h in 8% O2. Both procedures produce neuronal loss in the striatum and sensorimotor cortex. Nonlesioned controls were included. We scored percent forepaw placement on the edge of a horizontal surface, with lateral vibrissa stimulation, from P9 to P19, and at P33 and P50. Then, on P50, rats were treated with the NMDA antagonist MK-801 to determine whether deficits could be reinstated. NMDA- and HI-lesioned rats exhibited a deficit in contralateral vibrissa-stimulated forepaw placing that emerged during the second week of life. Yet, by P33 and P50, the lesioned groups and controls were indistinguishable. MK-801 injection on P50 resulted in transient reinstatement of the placing deficit. After unilateral neonatal excitotoxic or HI brain injury, contralateral sensorimotor deficits are detected, but in many animals, these deficits have resolved by adulthood. Thus, timing of sensorimotor tests may influence their sensitivity for detection of focal neuropathology originating in the neonatal period.

• Authors: Barbara T Felt, Timothy Schallert, Jie Shao, Yiqing Liu, Xiaoling Li, John D E Barks
• Journal: Developmental neuroscience (Dev Neurosci) Vol. 24 Issue 5 Pg. 418-25 ( 2002) ISSN: 0378-5866 [Print] Switzerland
• PMID: 12640181 (Publication Type: Journal Article)
• Copyright: Copyright 2002 S. Karger AG, Basel

Chemical References

• Excitatory Amino Acid Agonists
• Excitatory Amino Acid Antagonists
• N-Methylaspartate
• Dizocilpine Maleate

Topics

• Animals
• Animals, Newborn
• Brain (growth & development, metabolism, pathology)
• Dizocilpine Maleate (pharmacology)
• Excitatory Amino Acid Agonists (administration & dosage, pharmacology)
• Excitatory Amino Acid Antagonists (pharmacology)
• Forelimb (innervation)
• Functional Laterality
• Hypoxia-Ischemia, Brain (metabolism, physiopathology)
• Injections, Intraventricular
• Motor Activity (drug effects)
• N-Methylaspartate (administration & dosage, antagonists & inhibitors, pharmacology)
• Neuronal Plasticity
• Rats
• Rats, Sprague-Dawley
• Recovery of Function (physiology)
• Time Factors
• Vibrissae (physiology)