Nitric Oxide Donors as Neuroprotective Agents after an Ischemic Stroke-Related Inflammatory Reaction

Marisol Godínez-Rubí,Argelia E Rojas-Mayorquín,Daniel Ortuño-Sahagún

doi:10.1155/2013/297357

Marisol Godínez-Rubí, Argelia E Rojas-Mayorquín + Show 1 more

Open Access

https://doi.org/10.1155/2013/297357

Copy DOI

Abstract

Cerebral ischemia initiates a cascade of detrimental events including glutamate-associated excitotoxicity, intracellular calcium accumulation, formation of Reactive oxygen species (ROS), membrane lipid degradation, and DNA damage, which lead to the disruption of cellular homeostasis and structural damage of ischemic brain tissue. Cerebral ischemia also triggers acute inflammation, which exacerbates primary brain damage. Therefore, reducing oxidative stress (OS) and downregulating the inflammatory response are options that merit consideration as potential therapeutic targets for ischemic stroke. Consequently, agents capable of modulating both elements will constitute promising therapeutic solutions because clinically effective neuroprotectants have not yet been discovered and no specific therapy for stroke is available to date. Because of their ability to modulate both oxidative stress and the inflammatory response, much attention has been focused on the role of nitric oxide donors (NOD) as neuroprotective agents in the pathophysiology of cerebral ischemia-reperfusion injury. Given their short therapeutic window, NOD appears to be appropriate for use during neurosurgical procedures involving transient arterial occlusions, or in very early treatment of acute ischemic stroke, and also possibly as complementary treatment for neurodegenerative diseases such as Parkinson or Alzheimer, where oxidative stress is an important promoter of damage. In the present paper, we focus on the role of NOD as possible neuroprotective therapeutic agents for ischemia/reperfusion treatment.

Highlights

When the brain blood flow is interrupted, it results in deprivation of oxygen and nutrients to the cells; this situation constitutes an ischemic stroke
Nitric Oxide Donors (NOD) inhibited the expression of cell adhesion molecules and infiltration of vascular immune cells into the Central nervous system (CNS), which subsequently led to reduction in the expression of proinflammatory cytokines at the site of injury
The great variability in the observed effects elicited by NOD, from neuroprotection to toxicity, could be due to the great diversity in doses used in the experiments, which are mainly distant from the existing physiological concentrations

Summary

Introduction

When the brain blood flow is interrupted, it results in deprivation of oxygen and nutrients to the cells; this situation constitutes an ischemic stroke. The increase in intracellular Ca2+ in neurons and glial cells initiates a set of nuclear and cytoplasmic events that produce deep brain tissue damage that includes the following: Ca2+ mitochondrial overload (which compromises the already affected ATP production and promotes the opening of the mitochondrial transition pore); the increase in OS, and the activation of a number of Ca2+-dependent enzymes. Such enzymes include proteases, kinases, phospholipases, and endonucleases, which destroy biomolecules [10]. Agents capable of modulating both elements will constitute promising therapeutic solutions [22,23,24,25]

Ischemic Lesion and Immune Response

Concluding Remarks