AUTHOR=Gu Wenquan , Bai Yingnan , Cai Jianguo , Mi Honglan , Bao Yinghui , Zhao Xinxin , Lu Chen , Zhang Fengchen , Li Yue-hua , Lu Qing 

TITLE=Hypothermia impairs glymphatic drainage in traumatic brain injury as assessed by dynamic contrast-enhanced MRI with intrathecal contrast

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 17 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2023.1061039

DOI=10.3389/fnins.2023.1061039

ISSN=1662-453X

ABSTRACT=The impact of hypothermia on the impaired drainage function of the glymphatic system in traumatic brain injury (TBI) is not understood. The present study used dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with intrathecal administration of low- and high-molecular-weight contrast agents (Gd-DTPA and hyaluronic acid conjugated Gd-DTPA) to investigate whether early brain hypothermia could improve glymphatic function after brain trauma. Male Sprague–Dawley rats undergoing controlled cortical impact injury were subjected to hypothermia or normothermia treatment. The qualitative and semiquantitative results of DCE-MRI obtained from all examined perivascular spaces and most brain tissue regions demonstrated a significant impairment of glymphatic drainage function among all TBI animals. This glymphatic drainage dysfunction was exacerbated when additional hypothermia was applied. The early glymphatic drainage reduction induced by TBI and aggravated by hypothermia was linearly related to the late increased deposition of p-tau and beta-amyloid revealed by histopathologic and biochemical analysis and cognitive impairment assessed by the Barnes maze and novel object recognition test. The glymphatic system dysfunction induced by hypothermia may be an indirect alternative pathophysiological factor indicating injury to the brain after TBI. Longitudinal studies and targeted glymphatic dysfunction management are recommended to explore the potential effect of hypothermia in TBI.