Neurotrophin potentiation of iron-induced spinal cord injury.

Abstract:

:Previous studies have shown that pretreatment with neurotrophins can potentiate the vulnerability of cultured neurons to excitotoxic and free radical-induced necrosis, in contrast to their well known neuroprotective effects against apoptosis. Here we tested the hypothesis that this unexpected injury-potentiating effect of neurotrophins would also take place in the adult rat spinal cord. Fe(3+)-citrate was injected stereotaxically into spinal cord gray matter in adult rats in amounts sufficient to produce minimal tissue injury 24 h later. Twenty-four-hour pretreatment with brain-derived neurotrophic factor, neurotrophin-3, or neurotrophin-4/5, but not nerve growth factor, markedly enhanced tissue injury in the gray matter as evidenced by an increase in the damaged area, as well as the loss of neurons and oligodendrocytes. Consistent with maintained free radical mediation, the neurotrophin-potentiated iron-induced spinal cord damage was blocked by co-application of the antioxidant N-tert-butyl-(2-sulfophenyl)-nitrone. These data support the hypothesis that the overall neuroprotective properties of neurotrophins in models of acute injury to the spinal cord may be limited by an underlying potentiation of free radical-mediated necrosis.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Mcdonald JW,Stefovska VG,Liu XZ,Shin H,Liu S,Choi DW

doi

10.1016/s0306-4522(02)00342-1

keywords:

subject

Has Abstract

pub_date

2002-01-01 00:00:00

pages

931-9

issue

3

eissn

0306-4522

issn

1873-7544

pii

S0306452202003421

journal_volume

115

pub_type

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