NMDA-receptor antagonist protects neurons from secondary degeneration after partial optic nerve crush - PubMed (original) (raw)

NMDA-receptor antagonist protects neurons from secondary degeneration after partial optic nerve crush

E Yoles et al. J Neurotrauma. 1997 Sep.

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Abstract

Damage resulting from a partial acute lesion of white matter in the central nervous system (CNS) gradually spreads also to neurons that escaped the primary injury, resulting in their degeneration. Such spreading has been referred to as secondary degeneration. In order to demonstrate that this degeneration is indeed secondary to that caused by the acute insult, as well as to investigate the mechanism underlying the spread of damage and ways in which to protect neurons from such damage, we have proposed the use of partial lesion of the rodent optic nerve as a model. In this model we examined whether an antagonist of a receptor-mediated channel, shown to be beneficial in gray matter lesions, can protect neurons from undergoing secondary degeneration following white matter lesion. A well-calibrated partial crush lesion inflicted on the optic nerve of adult rats was immediately followed by a single intraperitoneal injection of the N-methyl-D-aspartate receptor antagonist, MK-801 (1 mg/kg). Protection of neurons from secondary degeneration was assessed by retrograde labeling and by measurement of the visual evoked potential (VEP) response to light. Two weeks after the injury, the mean number of neurons that were still intact was about threefold higher in the MK-801-treated group than in the saline-treated control group, indicating a treatment-induced protection of neurons that had escaped primary injury. A positive VEP response to light was obtained in 90% of the MK-801 treated animals and in only 50% of injured controls. The questions regarding whether the secondary degeneration of initially spared neurons starts in their cell bodies or in their axons, and consequently the identity of the primary site of their protection by MK-801, are discussed in relation to the absence of N-methyl-D-aspartate receptors on nerve fibers. The present findings may have implications for both acute and chronic injuries of the CNS.

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