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Abstract
Cellular respiration is a vital process for the existence of life. Any condition that results in deprivation of oxygen (also termed as hypoxia) may eventually lead to deleterious effects on the functioning of tissues. Brain being the highest consumer of oxygen is prone to increased risk of hypoxia-induced neurological insults. This in turn has been associated with many diseases of central nervous system (CNS) such as stroke, Alzheimer's, encephalopathy etc. Although several studies have investigated the pathophysiological mechanisms underlying ischemic/hypoxic CNS diseases, the knowledge about protective therapeutic strategies to ameliorate the affected neuronal cells is meager. This has augmented the need to improve our understanding of the hypoxic and ischemic events occurring in the brain and identify novel and alternate treatment modalities for such insults. MicroRNA (miRNAs), small non-coding RNA molecules, have recently emerged as potential neuroprotective agents as well as targets, under hypoxic conditions. These 18–22 nucleotide long RNA molecules are profusely present in brain and other organs and function as gene regulators by cleaving and silencing the gene expression. In brain, these are known to be involved in neuronal differentiation and plasticity. Therefore, targeting miRNA expression represents a novel therapeutic approach to intercede against hypoxic and ischemic brain injury. In the first part of this review, we will discuss the neurophysiological changes caused as a result of hypoxia, followed by the contribution of hypoxia in the neurodegenerative diseases. Secondly, we will provide recent updates and insights into the roles of miRNA in the regulation of genes in oxygen and glucose deprived brain in association with circadian rhythms and how these can be targeted as neuroprotective agents for CNS injuries. Finally, we will emphasize on alternate breathing or yogic interventions to overcome the hypoxia associated anomalies that could ultimately lead to improvement in cerebral perfusion.
Highlights
Mammalian brain lacks fuel reservoirs and needs a constant supply of glucose for ATP generation, cell survival, and production of neurotransmitters
Hypoxia associated central nervous system (CNS) anomalies, such as stroke, Alzheimer’s, ischemic retinopathy, and encephalopathy are all linked with some common pathophysiological attributes that could be targeted for therapeutics
Suarez et al (2008) generated two Dicer knockout mouse cell lines, which were endothelial specific (Suarez et al, 2008). These findings suggest that the role of miRNA in modulation of miRNA and Yoga-Based Neurotherapeutics distinct aspects of angiogenesis might prove to be worthwhile in many human pathological diseases, especially those involving the vasculature
Summary
Mammalian brain lacks fuel reservoirs and needs a constant supply of glucose for ATP generation, cell survival, and production of neurotransmitters. It constitutes only 2% of body weight, it consumes nearly a quarter of total body glucose (∼5.6 mg glucose per 100 g human brain tissue per minute) (Erbslöh et al, 1958). Any hindrance in the oxygen supply to the brain may cause catastrophic effects to brain cells. In this review we will first discuss the pathophysiological effects caused due to hypoxia, which has been associated with different neurodegenerative diseases and consecutively, we will discuss miRNA based therapeutic approach to target the hypoxia-associated CNS injuries along with alternate therapies for management of hypoxia
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