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

Wenquan Gu; Yingnan Bai; Jianguo Cai; Honglan Mi; Yinghui Bao; Xinxin Zhao; Chen Lu; Fengchen Zhang; Yue-Hua Li; Qing Lu

doi:10.3389/fnins.2023.1061039

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

Front Neurosci. 2023 Feb 2:17:1061039. doi: 10.3389/fnins.2023.1061039. eCollection 2023.

Authors

Wenquan Gu¹, Yingnan Bai², Jianguo Cai³, Honglan Mi⁴, Yinghui Bao⁵, Xinxin Zhao⁴, Chen Lu⁶, Fengchen Zhang⁵, Yue-Hua Li⁷, Qing Lu⁸

Affiliations

¹ Department of Radiology, Shanghai Punan Hospital of Pudong New Area, Shanghai, China.
² Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
³ Department of Radiology, Xinhua Hospital Chongming Branch, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁴ Department of Radiology, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China.
⁵ Department of Neurology, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China.
⁶ Shanghai Weiyu International School, Shanghai, China.
⁷ Department of Radiology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
⁸ School of Medicine, Shanghai East Hospital, Tongji University, Shanghai, China.

Abstract

Introduction: The impact of hypothermia on the impaired drainage function of the glymphatic system in traumatic brain injury (TBI) is not understood.

Methods: Male Sprague-Dawley rats undergoing controlled cortical impact injury (CCI) were subjected to hypothermia or normothermia treatment. The rats undergoing sham surgery without CCI were used as the control. 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) was performed after TBI and head temperature management. The semiquantitative kinetic parameters characterizing the contrast infusion and cleanout in the brain, including influx rate, efflux rate, and clearance duration, were calculated from the average time-intensity curves.

Results and discussion: The qualitative and semiquantitative results of DCE-MRI obtained from all examined perivascular spaces and most brain tissue regions showed a significantly increased influx rate and efflux rate and decreased clearance duration among all TBI animals, demonstrating a significant impairment of glymphatic drainage function. 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.

Keywords: contrast agent; glymphatic function; hypothermia (HT); magnetic resonance imaging (MRI); traumatic brain injury.

Grants and funding

This work was supported by the National Natural Science Foundation of China (81871329 and 81900434), the Fudan University (IDF152064/016), the National Natural Science Foundation of Shanghai (19ZR1408900) (YBai), the Key Subspecialty Construction Funding of the Pudong Health System (PWZy2020–15) (WG), the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (2016427), the Excellent Discipline Leader of the Shanghai Municipal Planning Commission (2017BR041), and the Shanghai Key Discipline of Medical Imaging (2017ZZ02005) (Y-HL).