Longitudinal MRI evaluation of neuroprotective effects of pharmacologically induced hypothermia in experimental ischemic stroke |
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| Institution: | 1. Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, United States;2. Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA 30322, United States;3. Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States;4. Department of Drug Discovery Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425, United States;5. JT Pharmaceuticals Inc., Mt. Pleasant, SC 29464, United States;6. Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, GA 30033, United States;7. Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, United States;1. Department of Radiology, University of Chicago, Chicago, IL, USA;2. Medicine, Hematology/Oncology, University of Chicago, Chicago, IL, USA;1. Biomedical Engineering, Vanderbilt University, Nashville, TN, USA;2. Vanderbilt University, Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA;3. Computer Science, Vanderbilt University, Nashville, TN, USA;4. Electrical Engineering, Vanderbilt University, Nashville, TN, USA;1. Aging Research Center (ARC), Karolinska Institute and Stockholm University, Sweden;2. MRI Research Center, Karolinska University Hospital, Sweden;1. Department of Radiology, University Hospital Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany;2. Philips Healthcare, Röntgenstrasse 22, 22335 Hamburg, Germany;3. IMBIE (Statistics Department), University Hospital Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany;1. Department of Cardiology, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, People''s Republic of China;2. Institute of Cardiovascular Diseases, Shanghai Jiaotong University School of Medicine, Shanghai 200025, People''s Republic of China |
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| 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. |
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