Neurogenic inflammation after traumatic brain injury and its potentiation of classical inflammationReport as inadecuate




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Journal of Neuroinflammation

, 13:264

First Online: 11 October 2016Received: 06 September 2016Accepted: 28 September 2016

Abstract

BackgroundThe neuroinflammatory response following traumatic brain injury TBI is known to be a key secondary injury factor that can drive ongoing neuronal injury. Despite this, treatments that have targeted aspects of the inflammatory pathway have not shown significant efficacy in clinical trials.

Main bodyWe suggest that this may be because classical inflammation only represents part of the story, with activation of neurogenic inflammation potentially one of the key initiating inflammatory events following TBI. Indeed, evidence suggests that the transient receptor potential cation channels TRP channels, TRPV1 and TRPA1, are polymodal receptors that are activated by a variety of stimuli associated with TBI, including mechanical shear stress, leading to the release of neuropeptides such as substance P SP. SP augments many aspects of the classical inflammatory response via activation of microglia and astrocytes, degranulation of mast cells, and promoting leukocyte migration. Furthermore, SP may initiate the earliest changes seen in blood-brain barrier BBB permeability, namely the increased transcellular transport of plasma proteins via activation of caveolae. This is in line with reports that alterations in transcellular transport are seen first following TBI, prior to decreases in expression of tight-junction proteins such as claudin-5 and occludin. Indeed, the receptor for SP, the tachykinin NK1 receptor, is found in caveolae and its activation following TBI may allow influx of albumin and other plasma proteins which directly augment the inflammatory response by activating astrocytes and microglia.

ConclusionsAs such, the neurogenic inflammatory response can exacerbate classical inflammation via a positive feedback loop, with classical inflammatory mediators such as bradykinin and prostaglandins then further stimulating TRP receptors. Accordingly, complete inhibition of neuroinflammation following TBI may require the inhibition of both classical and neurogenic inflammatory pathways.

KeywordsCaveolae Neuroinflammation Neurokinin 1 receptor Substance P Traumatic brain injury AbbreviationsAMTAbsorptive-mediated transcytosis

BBBBlood-brain barrier

CNSCentral nervous system

EPOErythropoietin

RMTReceptor-mediated transcytosis

SPSubstance P

TLRToll-like receptor

TRP channelsTransient receptor potential cation channels

TBITraumatic brain injury

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Author: Frances Corrigan - Kimberley A. Mander - Anna V. Leonard - Robert Vink

Source: https://link.springer.com/







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