Matrix metalloproteinases in ischemia- reperfusion injury in brain: Antioxidants as rescuer

Cerebral ischemia-reperfusion (CIR) injury exerts a potential threat on neuronal cell survival. Cerebral ischemia, a type of stroke, ensues due to occlusion of oxygen in common carotid arteries and blockage of nutrients in brain tissues. It is the most common and lethal neurological disorder especially in the aged individuals. When neuronal cells become deprived of sufficient oxygen because of low blood flow rate following ischemic stroke, a cascade of events occurs, leading to cell death by toxicity and oxidative stress. Oxidative stress appears to be an important role in CIR injury wherein a large amount of reactive oxygen species generated by the mitochondria provokes the release of cytochrome c and other apoptotic proteins, leading to defective gene expression and subsequent cell death. Under CIR, natural defense mechanism fails to protect neurons from oxidative damage. Matrix metalloproteinases (MMPs), mainly MMP-2 and MMP-9, are elevated after cerebral ischemia which are involved in accelerating matrix degradation, disrupting the blood-brain barrier (BBB), and increasing the neuronal infarct size. Some compounds (flavonoids, antioxidants, MMP inhibitors) show the potency as neuroprotectant against CIR. Question arises how to reduce the cytotoxicity of the compounds and overcome the BBB permeability? Over the past few years, different vesicular formulations, especially liposome and nanocapsule, have received attention as effective modality in enhancing therapeutic concentration while rescuing CIR. This chapter is focused on the mechanism of MMPs' action during CIR injury and to delineate the effect of MMP inhibitors and antioxidants with their different formulations in modulating MMP activity.