Inhibition of lipid peroxidation attenuates axotomy-induced apoptotic degeneration of facial motor neurons in neonatal rats

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 acetyl‐transferase 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. © 1996 Wiley‐Liss, Inc.

(-)-Epigallocatechin-3-Gallate Modulates Spinal Cord Neuronal Degeneration by Enhancing Growth-Associated Protein 43, B-Cell Lymphoma 2, and Decreasing B-Cell Lymphoma 2-Associated X Protein Expression after Sciatic Nerve Crush Injury

“…Both Hall and colleagues and Smith and colleagues showed that it was lipid peroxidation (LPO) that was responsible for inducing apoptotic neural death in rats. 50,51 However, a future study is planned to fully investigate this relation.…”

High dose erythropoietin promotes functional recovery of rats following facial nerve crush

“…These include the expression of high levels of excitatory amino acids and their analogues 17 and the generation of free radicals. 18 In recent years, Epo has been proven as a potent agent to protect neurons from death in a variety of models of neurodegenerative diseases in the central nervous system. [19][20][21][22] The mechanisms behind the ability of Epo to produce neuroprotective effects are proposed to be reduction in glutamate toxicity, increased production of neuronal anti-apoptotic factors, reduced nitric oxide-mediated injury, anti-inflammatory effects, and anti-oxidant properties.…”

Neutralization of the chemokine CXCL10 reduces apoptosis and increases axon sprouting after spinal cord injury

“…Apoptosis is mediated by an intrinsic pathway characterized by mitochondrial dysfunction, leading to an increase in oxidative stress (Hall, 1993; Hall et al, 1996; Sullivan et al, 2004). Inflammation contributes to oxidative stress via the release of free radicals during the early stages of secondary degeneration (Dumont et al, 2001).…”