Longitudinal MRI evaluation of neuroprotective effects of pharmacologically induced hypothermia in experimental ischemic stroke

• Type of Material: Article
• Authors: Silun Wang, Emory University; Xiohuan Gu, Emory University; Ramesh Paudyal, Emory University; Ling Wei, Emory University; Thomas A. Dix, Medical University of South Carolina; Shan Ping Yu, Emory University; Xiaodong Zhang, Emory University
• Language: English
• Date: 2017-07-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.mri.2017.03.011
• Title of Journal or Parent Work: Magnetic Resonance Imaging
• ISSN: 0730-725X
• Volume: 40
• Start Page: 24
• End Page: 30
• Grant/Funding Information: The authors thank Ruth Connelly, Paul Chen, and Doty Kempf (DVM) for animal handling. This project was supported in part by NCRR (P51RR000165) and currently by the Office of Research Infrastructure Programs of NIH (OD P51OD011132).; It is also supported by NIH grants NS085568, R44NS90629, and a VA Merit grant RX000666.
• Keywords: MRI; FOCAL CEREBRAL-ISCHEMIA; MODERATE HYPOTHERMIA; Radiology, Nuclear Medicine & Medical Imaging; WEIGHTED MRI; Ischemic stroke; TRAUMATIC BRAIN-INJURY; Logarithm pattern; Life Sciences & Biomedicine; DIFFUSION; Drug-induced hypothermia; HPI201; MICE; MODEL; NEUREGULIN-1; Science & Technology; TEMPERATURE; THERAPEUTIC HYPOTHERMIA
• Research Categories: Health Sciences, Radiology; Physics, General; Health Sciences, Medicine and Surgery

Abstract

Pharmacologically induced hypothermia (PIH) shows promising neuroprotective effects after stroke insult. However, the dynamic evolution of stroke infarct during the hypothermic therapy has not been understood very well. In the present study, MRI was utilized to longitudinally characterize the infarct evolution in a mouse model of ischemic stroke treated by PIH using the neurotensin agonist HPI201. Adult male C57BL/6 mice underwent permanent occlusion of the right middle cerebra artery (MCA). Each animal received a vehicle or HPI201 intraperitoneal injection. The temporal changes of stroke lesion were examined using T2-weighted imaging and diffusion-weighted imaging (DWI) in the acute phase (1 − 3h) and 24 h post stroke. Significantly reduced infarct and edema volumes were observed in PIH treated stroke mice, in agreement with TTC staining findings. Also, the TUNEL staining results indicated apoptotic cells were widely distributed among the ischemic cortex in control group but limited in PIH treated mice. Dramatically reduced growth rate of infarction was seen in PIH treated stroke mice. These results demonstrate HPI201 has strong neuroprotection effects during acute stroke. In particular, MRI with the numerical modelling of temporal infarct evolution could provide a unique means to examine and predict the dynamic response of the PIH treatment on infarct evolution.