Sustained, long-lasting inhibition of nitric oxide synthase aggravates the neural damage in some models of excitotoxic brain injury
| Autor: | Elisabetta Ciani, Antonio Contestabile, Ivan Baldinotti |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Male
Kainic acid Neurotoxins Excitotoxicity Biology Pharmacology Endothelial NOS medicine.disease_cause Nitric Oxide Neuroprotection Nitric oxide Choline O-Acetyltransferase chemistry.chemical_compound medicine Excitatory Amino Acid Agonists Animals Enzyme Inhibitors Rats Wistar Ibotenic Acid Basal forebrain Kainic Acid Glutamate Decarboxylase General Neuroscience Neurotoxicity NADPH Dehydrogenase Brain medicine.disease Calcium Channel Blockers Immunohistochemistry Rats Nitric oxide synthase Neostriatum NG-Nitroarginine Methyl Ester chemistry Cholinergic Fibers Verapamil Basal Nucleus of Meynert Brain Injuries Nerve Degeneration biology.protein Nitric Oxide Synthase Neuroscience |
| Zdroj: | Brain research bulletin. 56(1) |
| ISSN: | 0361-9230 |
| Popis: | Brain nitric oxide (NO) can be a mediator of physiological and neuroprotective actions and an effector of neural damage. The effectiveness of acute or chronic inhibition of NO production in in vivo experiments of neurotoxicity/neuroprotection is controversial. We report here on the effects of a chronic, sustained inhibition of nitric oxide synthase (NOS) on the neurodegenerative damage caused by three different excitotoxic lesions. The damage caused by intrastriatal injection of ibotenic or kainic acid was aggravated in rats subjected to chronic NOS inhibition. On the contrary, the drop of cortical cholinergic input consequent to ibotenic acid-mediated degeneration of basal forebrain neurons was not altered by chronic NOS inhibition. The worsening of the damage was not related to any overt differential sensitivity to excitotoxicity of NOS-containing striatal neurons under conditions of NOS inhibition. These results suggest that, contrary to what has been often reported for short-term, mild inhibition of NO production, chronic and sustained NOS inhibition may exacerbate neuropathology. Thus, long-lasting shortage of NO may be detrimental when neuroprotective mechanisms related to the physiological action of this free radical are severely impaired. Although we cannot exclude that inhibition of the endothelial NOS isoform could have contributed to the worsening of neuropathology, differences among the paradigms of neurotoxicity used in the present study suggest a primary involvement of the neuronal NOS isoform. In view of the potential therapeutic use of NOS inhibitors, the effects of a too drastic alteration of the balance between neuroprotective and neurodegenerative actions of NO should be carefully considered. |
| Databáze: | OpenAIRE |
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