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Updated: Aug 14, 2026
Quantification of Neurovascular Protection Following Repetitive Hypoxic Preconditioning and Transient Middle Cerebral Artery Occlusion in Mice
Published on: May 4, 2015
Longitudinal MRI evaluation of neuroprotective effects of pharmacologically induced hypothermia in experimental
Silun Wang1, Xiaohuan Gu2, Ramesh Paudyal3
1Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, United States.
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.
Insights
Pharmacologically induced hypothermia (PIH) using HPI201 significantly reduces stroke infarct and apoptosis in mice. MRI monitoring revealed a dramatically reduced infarction growth rate, highlighting PIH
Area of Science:
- Neuroscience
- Medical Imaging
- Pharmacology
Background:
- Pharmacologically induced hypothermia (PIH) demonstrates neuroprotective potential post-stroke.
- The precise evolution of stroke infarcts under PIH therapy requires further elucidation.
Purpose of the Study:
- To longitudinally characterize stroke infarct evolution using MRI in a mouse model treated with PIH.
- To evaluate the neuroprotective efficacy of the neurotensin agonist HPI201.
Main Methods:
- Permanent middle cerebral artery occlusion (MCAO) in adult male C57BL/6 mice.
- Treatment with vehicle or HPI201, followed by longitudinal MRI (T2-weighted and DWI) at acute (1-3h) and 24h post-stroke.
- Assessment of infarct/edema volumes, TTC staining, and TUNEL staining for apoptosis.
Main Results:
- PIH treatment with HPI201 significantly reduced infarct and edema volumes compared to controls.
- TUNEL staining revealed decreased apoptotic cells in the ischemic cortex of PIH-treated mice.
- A dramatically reduced infarction growth rate was observed in the PIH-treated group.
Conclusions:
- HPI201 demonstrates significant neuroprotection in acute ischemic stroke.
- Longitudinal MRI and numerical modeling offer a valuable method to assess and predict PIH treatment response in stroke evolution.
