Loss of PAFR prevents neuroinflammation and brain dysfunction after traumatic brain injury

Xiang-Jie Yin,Zhen-Yan Chen,Jin-Jia Hu,Xiao-Na Zhu

doi:10.1038/srep40614

Abstract

Traumatic brain injury (TBI) is a principal cause of death and disability worldwide, which is a major public health problem. Death caused by TBI accounts for a third of all damage related illnesses, which 75% TBI occurred in low and middle income countries. With the increasing use of motor vehicles, the incidence of TBI has been at a high level. The abnormal brain functions of TBI patients often show the acute and long-term neurological dysfunction, which mainly associated with the pathological process of malignant brain edema and neuroinflammation in the brain. Owing to the neuroinflammation lasts for months or even years after TBI, which is a pivotal causative factor that give rise to neurodegenerative disease at late stage of TBI. Studies have shown that platelet activating factor (PAF) inducing inflammatory reaction after TBI could not be ignored. The morphological and behavioral abnormalities after TBI in wild type mice are rescued by general knockout of PAFR gene that neuroinflammation responses and cognitive ability are improved. Our results thus define a key inflammatory molecule PAF that participates in the neuroinflammation and helps bring about cerebral dysfunction during the TBI acute phase.

Highlights

Traumatic brain injury (TBI) is a principal cause of death and disability worldwide, which is a major public health problem
We found no difference of spatial learning and memory between WT mice and PAFR−/− mice in Morris water maze (MWM) task (Fig. 2a), the WT mice suffered from TBI spent longer time to found the target quadrant and showed lower accuracy compared to untreated WT mice and PAFR−/− mice, indicating an imparied memory in WT mice after TBI (Fig. 2b)
The present study revealed that platelet activating factor (PAF) and its associated receptor strongly mediates the inflammatory response after TBI

Summary

Introduction

Traumatic brain injury (TBI) is a principal cause of death and disability worldwide, which is a major public health problem. The abnormal brain functions of TBI patients often show the acute and long-term neurological dysfunction, which mainly associated with the pathological process of malignant brain edema and neuroinflammation in the brain. The function of brain is abnormal in patients of TBI who show an acute and long-term neurological dysfunction, which is caused mainly by the pathological process including malignant brain edema and inflammatory response[6,7]. TBI has long been known to give rise to acute classical secondary neurogenic inflammation associated with inflammatory cytokine release[14]. To determine the relationship between PAF and the inflammatory response after TBI, we explored development of inflammation in the brain of PAFR knockout in which the effects had on cognitive function.

Methods

Results

Conclusion