GM1 ganglioside treatment protects against long-term neurotoxic effects ofneonatal X-irradiation on cerebellar cortex cytoarchitecture and motor function

Exposure of neonatal rats to a 5 Gy dose of X-irradiation induces permanent abnormalities in cerebellar cortex cytoarchitecture (disarrangement of Pur kinje cells, reduction of thickness of granular cortex) and neurochemistry (late increase in noradrenaline levels), and motor function (ataxic gait). The neuroprotective effects of gangliosides have been demonstrated using a variety of CNS injuries, including mechanical, electrolytic, neurotoxic, is chemic, and surgical lesions. Here, we evaluated whether systemically admin istered GM1 ganglioside protects against the long-term CNS abnormalities in duced by a single exposure to ionizing radiation in the early post-natal pe riod. Thus, neonatal rats were exposed to 5 Gy X-irradiation, and subcutane ously injected with one dose (30 mg/kg weight) of GM1 on h after exposure f ollowed by three daily doses. Both at post-natal days 30 and 90, gait and c erebellar cytoarchitecture in X-irradiated rats were significantly impaired when compared to age-matched controls. By contrast, both at post-natal day s 30 and 90, gait in X-irradiated rats that were treated with GM1 was not s ignificantly different from that in non-irradiated animals. Furthermore, at post-natal day 90, cerebellar cytoarchitecture was still well preserved in GM1-treated, X-irradiated animals. GM1 failed to modify the radiation-indu ced increase in cerebellar noradrenaline levels. Present data indicate that exogenous GM1, repeatedly administered after neonatal X-irradiation, produ ces a long-term radioprotection, demonstrated at both cytoarchitectural and motor levels. (C) 2000 Elsevier Science B.V. All rights reserved.