The Role of Posttraumatic Hypothermia in Preventing Dendrite Degeneration and Spine Loss after Severe Traumatic Brain Injury

Chuan-Fang Wang,Ji-Yao Jiang,Jun-Feng Feng,Xiao Gu,Gan Jiang,Cheng-Cheng Zhao

doi:10.1038/srep37063

Chuan-Fang Wang, Ji-Yao Jiang + Show 4 more

Open Access

https://doi.org/10.1038/srep37063

Copy DOI

Abstract

Posttraumatic hypothermia prevents cell death and promotes functional outcomes after traumatic brain injury (TBI). However, little is known regarding the effect of hypothermia on dendrite degeneration and spine loss after severe TBI. In the present study, we used thy1-GFP transgenic mice to investigate the effect of hypothermia on the dendrites and spines in layer V/VI of the ipsilateral cortex after severe TBI. We found that hypothermia (33 °C) dramatically prevented dendrite degeneration and spine loss 1 and 7 days after CCI. The Morris water maze test revealed that hypothermia preserved the learning and memory functions of mice after CCI. Hypothermia significantly increased the expression of the synaptic proteins GluR1 and PSD-95 at 1 and 7 days after CCI in the ipsilateral cortex and hippocampus compared with that of the normothermia TBI group. Hypothermia also increased cortical and hippocampal BDNF levels. These results suggest that posttraumatic hypothermia is an effective method to prevent dendrite degeneration and spine loss and preserve learning and memory function after severe TBI. Increasing cortical and hippocampal BDNF levels might be the mechanism through which hypothermia prevents dendrite degeneration and spine loss and preserves learning and memory function.

Highlights

Posttraumatic mild hypothermia is an effective technique for reducing cerebral metabolism and oxygen consumption, diminishing cytotoxic oedema, stabilizing the blood-brain barrier (BBB), and promoting the survival rate after traumatic brain injury (TBI); it is widely applied in clinical practice[9]
One day after severe TBI, significant reductions (p < 0.01) in the number of dendrite branches and total length were observed in the TBI with normothermia group (TNG) and TBI with hypothermia group (THG) compared with the sham group (Fig. 1b)
Seven days after severe TBI, significant reductions (p < 0.01) in the number of dendrite branches and their total length were observed in the TNG compared with the sham group, whereas a reduction (p = 0.018) was only observed for the number of apical dendrite branches in the THG compared with the sham group (Fig. 2b)

Summary

Introduction

Posttraumatic mild hypothermia is an effective technique for reducing cerebral metabolism and oxygen consumption, diminishing cytotoxic oedema, stabilizing the blood-brain barrier (BBB), and promoting the survival rate after TBI; it is widely applied in clinical practice[9]. Several animal studies have revealed that posttraumatic hypothermia can prevent cell death and axonal degeneration after TBI10,11. We found that mild hypothermia significantly improved the outcomes of severe TBI compared with that of a www.nature.com/scientificreports/. The effects of posttraumatic hypothermia on TBI-induced dendrite degeneration and spine loss during the early phase of this condition remain unknown. We than applied therapeutic mild hypothermia treatment (33 °C) to investigate whether posttraumatic hypothermia affects dendrite protection and spine preservation at 1 and 7 days after TBI and determine the possible underlying mechanisms of this effect

Methods

Results

Conclusion