title: Longitudinal MRI evaluation of neuroprotective effects of pharmacologically induced hypothermia in experimental ischemic stroke.
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 24h 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.
authors.affiliation: Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, United States.
authors.forename: Silun
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA 30322, United States.
authors.forename: Xiaohuan
authors.initials: X
authors.lastname: Gu
authors.affiliation: Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, United States; Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Paudyal
authors.affiliation: Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA 30322, United States.
authors.forename: Ling
authors.initials: L
authors.lastname: Wei
authors.affiliation: Department of Drug Discovery Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425, United States; JT Pharmaceuticals Inc., Mt. Pleasant, SC 29464, United States.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Dix
authors.affiliation: Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA 30322, United States; Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, GA 30033, United States. Electronic address: spyu@emory.edu.
authors.forename: Shan P
authors.initials: SP
authors.lastname: Yu
authors.affiliation: Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, United States; Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, United States. Electronic address: xzhang8@emory.edu.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D004195:Disease Models, Animal; D007036:Hypothermia, Induced; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020768:Middle Cerebral Artery / Q000473:pathology*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020521:Stroke / Q000473:pathology*
chemical_list: D018696:Neuroprotective Agents
keywords: Drug-induced hypothermia; HPI201; Ischemic stroke; Logarithm pattern; MRI