DIABETIC NEUROPATHY: OXIDATIVE STRESS AND NEUROINFLAMMATION
*Monalisa Debnath and Dr. Shruti Agrawal
Diabetic neuropathy associated microvascular complications are the most painful, disabling and fatal outcomes with an aetiology of oxidative stress and neuroinflammation; acting as pathophysiological triggers damaging the peripheral nerves and brain cells. It progresses with decreased nerve functionality and nerve blood perfusion that may result in permanent neuronal damage. The clinical manifestations include numbness, burning, tingling sensation and intractable pain. Neuroinflammation initiates pathogenesis resulting in various brain diseases, including not only acute but also neurodegenerative mental disorders. Numerous epidemiological studies have documented an increase in plasma levels of inflammatory markers like CRP, IL-6 and TNF-α along with many other molecules like transforming growth factor-β (TGF-β), MCP1 or LP-PLA2 among patients with metabolic syndromes. Some of the major pathways that play a crucial role in the progression of diabetic neuropathy include polyol pathway, advanced glycation end products, altered activity of (Na⁺-K⁺)ATPase, poly-ADP ribose polymerase (PARP) over-activation and cyclo-oxygenase-2 activation. Nerve cells are prone towards hyperglycaemic injury as neuronal glucose uptake is based on external glucose concentration that is found to be 4-5 folds higher among the diabetic subjects. Drugs like chemical chaperons-trimethylamine oxide and 4- phenyl butyric; peroxynitrite decomposition catalysts, PARP inhibitors; and antioxidants like 𝛼-lipoic acid and N-acetyl cysteine have been found to target oxidative stress inflammatory pathways thus improving the sensorimotor and functional deficits associated with diabetic neuropathy. Still, a lot of work is warranted to further elucidate the cross talk of oxidative stress, mitochondrial dysfunction, and inflammation in the pathophysiology of diabetic neuropathy.
Keywords: Diabetic neuropathy, neuroinflammation, neuronal damage, microvascular complications.
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