Antioxidants and Neuroprotection in the Brain and Retina

Oxidative stress is implicated in the pathogenesis of a number of neurological disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis and stroke in the adult as well as in conditions such as periventricular white matter damage in the neonatal brain. It has also been linked to the disruption of blood brain barrier (BBB) in hypoxic-ischemic injury. Both experimental and clinical results have shown that antioxidants such as melatonin, a neurohormone synthesized and secreted by the pineal gland and edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a newly developed drug, are effective in reducing oxidative stress and are promising neuroprotectants in reducing brain damage. Indeed, the neuroprotective effects of melatonin in many central nervous system (CNS) disease conditions such as amyotrophic lateral sclerosis, PD, AD, ischemic injury, neuropsychiatric disorders and head injury are well documented. Melatonin affords protection to the BBB in hypoxic conditions by suppressing the production of vascular endothelial growth factor and nitric oxide which are known to increase vascular permeability. The protective effects of melatonin against hypoxic damage have also been demonstrated in newborn animals whereby it attenuated damage in different areas of the brain. Furthermore, exogenous administration of melatonin in newborn animals effectively enhanced the surface receptors and antigens on the macrophages/microglia in the CNS indicating its immunoregulatory actions. Not only did melatonin prevent neuronal loss in the brain, but also protected the retinal neurons in ocular diseases such as glaucoma, diabetic retinopathy and age related macular degeneration. Another anti-oxidant, edaravone has been shown to reduce oxidative stress, edema, infarct volume, inflammation and apoptosis following ischemic injury of the brain in the adult as well as decrease free radical production in the neonatal brain following hypoxic-ischemic insult. It can counteract toxicity from activated microglia. This review summarizes the clinical and experimental data highlighting the therapeutic potential of melatonin and edaravone in neuroprotection in various disorders of the CNS.

Keywords: Activated microglia, antioxidants, blood brain barrier disruption, edaravone, excitotoxicity, glutathione, hypoxia, inflammation, lipid peroxidation, malondialdehyde, melatonin, mitochondrial dysfunction, neurodegeneration, neuronal death, nitric oxide, oligodendrocytes death, oxidative stress, reactive oxygen species, retinal ganglion cell, vascular endothelial growth factor.