The Association Between Neuronal Nitric Oxide Synthase and Neuronal Sensitivity in the Brain After Brain Injury

Abstract

Injury to the central nervous system is the leading cause of disability in the United States. Neuronal death is one of the causes of disability. Among patients who survive this type of injury, various degrees of recovery in brain function are observed. The molecular basis of functional recovery is poorly understood. Clinical observations and research using experimental injury models have implicated several metabolites in the cascade of events that lead to neuronal degeneration. The levels of intracellular ATP (energy source) and pH are decreased, whereas levels of extracellular glutamate, intracellular calcium ions, and oxidative damage to RNA/DNA, protein, and lipid are increased. These initiating events can be associated with energy failure and mitochondrial dysfunction, resulting in functional or structural brain damage. The injured brain is known to express immediate early genes. Recent studies show that reactive oxygen species (ROS) cause lesions in genes from which mRNA is transcribed as part of the endogenous neuroprotective response. Although degenerating proteins and lipids may contribute to necrosis significantly after severe injury, abnormalities in genetic material, if not repaired, disturb cellular function at every level by affecting replication, transcription, and translation. These lesions include abnormal nucleic acids, known as oxidative lesions of DNA (ODLs) or of RNA (ORLs). In this review, we focus on our current understanding of the various effects of neuronal nitric oxide synthase on the formation of modified bases in DNA and RNA that are induced in the brain after injury, and how ODLs and ORLs affect cell function.

Aluminum and copper in drinking water enhance inflammatory or oxidative events specifically in the brain

“…During inflammation, an increase in NO production may increase the oxidative status of the CNS. The neuronal isoform of nitric oxide synthase (nNOS) is highly responsive to changes in oxidative stress (Liu et al, 2002). Perinatal exposure to Al (5 mM) in the drinking water increased the number of nNOS immunoreactive neurons in the frontal cortex of rat pups (Kim, 2003).…”

Revisión del traumatismo craneoencefálico

“…Si el vasoespasmo se asocia a un aporte sanguíneo bajo puede generar isquemia o infarto cerebral. Cuando en la fase final del período isquémico se produce la revascularización, la hiperoxemia tisular vinculada al mismo posibilitaría la extensión de la lesión más allá del foco o focos isquémicos 22,30,31,41 . También existe daño secundario en relación con causas .…”

“…En el transcurso de estas reacciones se libera una inmensa cantidad de superóxido. Este radical reacciona con el NO y genera peroxinitrito, el cual posee una vida media de 1-2 s y difunde en un radio de 100 μ. Ello le permite penetrar en el núcleo, e incluso en otras células, fuera de la que le dio origen, destruyendo porciones de ADN, ARN y otros componentes moleculares 22,36 . En resumen, bien por acción mecánica bien por isquemia, algunas áreas cerebrales quedarán irreversiblemente dañadas minutos a horas después del traumatismo, mientras que otras se alterarán tan sólo funcionalmente.…”

“…No se ha empleado, sin embargo, en la clínica humana 22 . 2) Unas 2 horas después del traumatismo, el cerebro expresa genes precoces (IEGs).…”

Endothelial Nitric Oxide Synthase and Neurodevelopmental Disorders

“…The actions of eNOS in endothelial dysfunction lead to vascular and metabolic disorders and are also implicated in hypoxic-ischemic brain injury [4]. Studies have shown that hypoxic brain injury is characterized by changes in vascular growth and endothelial dysfunction [5][6][7][8]. Despite the widespread conirmation a signiicant role for NO in physiological and pathological vascular homeostasis, the role of NO in the pathogenesis of perinatal brain injury has not been fully investigated.…”