Published: 1999
Total Pages: 101
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Background and Purpose: Injury to the central nervous system (CNS) in general, and to the visual system (retina or optic nerve) in particular, has a final outcome which is far more severe than the initial damage. If neighboring neurons that escaped the initial insult are to be rescued from eventual degeneration, ways must be found protect them. Adequate neuroprotection presupposes a basic understanding of the way in which the damage spreads, the nature of the mediators of toxicity, the most efficient means of neutralizing these harmful agents or their effects, and ways of making the neural tissue more resistant to the toxicity mediators. Methods: Our choice of model for studying mediators of toxicity and methods of neuroprotection is a partial crush injury of the rat optic nerve. Results: Partial injury of the rat optic nerve leads to a gradual spread of damage from the injured neurons, commencing in either the axons or the cell bodies of adjacent neurons that escaped initial injury. The continuing degeneration is associated with an increase in extracellular glutamate and nitric oxide, and possibly also an increased susceptibility of the spared neurons to the toxicity. We have provided evidence that the immune response, in the form of autoimmune T cells directed against the CNS self antigen myelin basic protein, if suitably boosted, is beneficial in reducing the spread of damage. Conclusion: Partial lesion of the optic nerve results in a self perpetuating and self limiting spread of neuronal damage, which is mediated in part by a toxic increase in physiological compounds, in combination with an increased susceptibility of the affected neurons. Autoimmunity, if suitably controlled, may-be a benign response adapted for the protection and maintenance of the damaged tissue.