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.
