The nitric oxide donor LA 419 decreases brain damage in a focal ischemia model.
Stroke affects a large number of people, especially in developed countries, but treatment options are limited. Over the years, it has become clear that nitric oxide (NO) plays a major role in this pathology and that treatments that either reduce or increase NO presence may provide an alternative route for reducing the sequelae of brain ischemia. The NO donor LA 419 previously has been shown to protect the brain tissue from ischemic damage in an experimental model of global brain ischemia. Here we study whether this holds true for focal ischemia, a condition closer to the more common form of human stroke. Ischemia was induced in rats by a stereotaxic injection of endothelin-1, a potent vasoconstrictor, in the striatum. Seven days after the injection, magnetic resonance imaging (MRI) found a significant elevation in apparent diffusion coefficient (ADC) in the injected striatum of untreated rats, due to ischemia-induced vascular edema. Animals that received LA 419 prior to injection with endothelin-1 showed an ADC undistinguishable from the contralateral striatum or from the striatum of rats not treated with LA 419. In addition, immunohistochemistry with antibodies against neuronal nitric oxide synthase (nNOS), inducible NOS (iNOS), and nitrotyrosine showed a marked increase in the expression of these markers of NO production following ischemic treatment that was dampened by treatment with LA 419. In summary, our results clearly show that the NO donor LA 419 may be a useful compound for the prevention and/or treatment of focal brain ischemia.
Martínez-Murillo
Ricardo
R
Department of Neuroanatomy and Cell Biology, Instituto Cajal, CSIC, Avenida del Doctor Arce 37, 28002 Madrid, Spain.
Fernández
Ana Patricia
AP
Serrano
Julia
J
Rodrigo
José
J
Salas
Eduardo
E
Mourelle
Marisabel
M
Martínez
Alfredo
A
D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D007511:Ischemia / Q000150:complications*; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D020030:Nitric Oxide Donors / Q000627:therapeutic use*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
C503157:LA 419; D020030:Nitric Oxide Donors; C002744:3-nitrotyrosine; D014443:Tyrosine; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D007548:Isosorbide Dinitrate