Investigations on the Reno Neural biomolecules in acute kidney injury

Abstract

Acute kidney injury is a multifarious disorder which leads to abrupt reduction in kidney function causing accumulation of nitrogenous wastes in the body. This pathophysiologic underpinnings of the disease lead to inflammatory cascade and neuro-inflammation which gradually leads to cognitive changes, pain and intonation in the nervous system. Bioinformatics text mining approach for AKI shows that more than 600 genes participate in manifestation of pain in AKI. Out of these, 12 genes participate in neuro-immune axis leading to pain pathways. 10 of these 12 genes played a role in pro-neuroinflammation while remaining 2 in anti-neuroinflammation. Cystoscape analysis shows that the instigation of CGRP and its cross talk with TNF-and#945; is mediated by TPRV1, PTGER4 and CRLR. In-vivo analysis on Balb/c mice shows that mRNA expression of CGRP, TNF-and#945;, TRPV1, CRLR and PTGER4 modulate with progression of injury in kidney and brain tissues. The variation was also reflected in a similar pattern by immuno-histology and ELISA. The BBB was found permeable with progression of injury. Inflammation was reversed with dose of infliximab by injecting in FA dosed mice. The kidney tissues were analysed for CGRP mRNA expression and it was observed that in a combined dose of infliximab and FA, CGRP expression reverses in 12 and 24 hours. This shows that modulation of pain is dependent on neuro-inflammation derived from TNF-and#945; routed via neuropeptide CGRP. newline