Inhibition of lipid peroxidation attenuates axotomy-induced apoptotic degeneration of facial motor neurons in neonatal rats.
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| Abstract |
The purpose of this study was to investigate the role of oxygen radical-induced lipid peroxidative mechanisms in trophic deprivation-induced apoptotic motor neuronal degeneration by testing the ability of the 21-aminosteroid lipid peroxidation inhibitor tirilazad mesylate (U-74006F) to attenuate the retrograde degeneration of facial motor neurons following axotomy in 14-day-old rat pups. On day 0, the right facial nerve of each rat was transected at its point of exit from the stylomastoid foramen. Pups were treated orally with either 10 or 30 mg/kg U-74006F or cyclodextrin vehicle 10 min before axotomy, and post-treated once a day from days 1 to 6, and then once every other day from days 8 to 21. The rats were sacrificed 3 weeks post-transection and the surviving motor neurons, identified through choline acetyltransferase immunocytochemistry, were counted in three regions (planes) in the facial nucleus. In vehicle-treated rats, 56.2% (region A), 50.6% (region B), and 57.4% (region C) of the motor neurons in the ipsilateral facial nucleus survived 21 days following facial nerve axotomy in comparison to the non-axotomized contralateral nucleus (P < 0.0001). Treatment with 10 mg/kg U-74006F significantly enhanced motor neuron survival in regions B and C to 72.8% (P < 0.01) and 66.7% (P < 0.02%), respectively. The 30 mg/kg dose level also increased survival rates to 64.2% (P < 0.02) and 67.9% (P < 0.01), respectively. A second experiment demonstrated that oral dosing with U-74006F (30 mg/kg), when limited to the first 5 days after axotomy, also significantly blunted retrograde degeneration measured at 21 days post-axotomy. The efficacy of the lipid peroxidation inhibitor U-74006F in protecting a portion of the facial motor neuron pool from post-axotomy degeneration suggests that lipid peroxidation may play a mechanistic role in trophic deprivation-induced apoptotic neuronal death.
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| Authors | E D Hall, S L Smith, J A Oostveen |
| Journal | Journal of neuroscience research (J Neurosci Res) Vol. 44 Issue 3 Pg. 293-9 (May 01 1996) ISSN: 0360-4012 [Print] United States |
| PMID | 8723768 (Publication Type: Journal Article) |
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