The neuro-inflammation and excitotoxicity in perinatal brain injury: The emerging role of brain mast cells

Abstract

Perinatal brain injury is a serious neurodevelopmental problem that can be occurred in preterm and term newborn infants. It is well established that neuro-inflammation is implicated in the pathophysiology of perinatal brain injury. The excitotoxicity is considered as a common molecular mechanism of perinatal brain injury. These insults are capable of leading to neuro-inflammation, but however neuro-inflammation is also able to induce the excitotoxicity in the developing brain. Thus, neuro-inflammation is both a cause and a consequence of excitotoxicity resulting in the brain damages during perinatal period. Excessive glutamate accumulation in the synaptic cleft in the brain is a prominent mechanism in the excitotoxicity while vasoactive and pro-inflammatory mediators such as histamine, prostaglandins, interleukin 1 (IL-1) β and tumor necrosis factor (TNF)-α released from brain-resident immune cells play a major role in neuro-inflammation that lead to the brain damages. Although the role of brain-resident microglial cells has been well documented in these neuro-inflammation processes, evidence for the role of brain mast cells (BMCs) has recently begun to emerge. Growing evidence indicates that brain mast cells are first responders of inflammatory insults in the developing brain and their activation is involved in induced brain injury.

We have recently demonstrated that ibotenate-induced excitotoxicity leads to the activation of brain mast cells in a model of ibotenate-induced brain injury in newborn rats. Thus, in this review we point out the current knowledge on the bidirectional role of brain mast cells in neuro-inflammation and excitotoxicity underlying perinatal brain injury.