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Optogenetic Spreading Depolarizations Do Not Worsen Acute Ischemic Stroke Outcome
Kazutaka Sugimoto1,2, Joanna Yang1, Paul Fischer1
1Departments of Radiology (K.S., J.Y., P.F., T.T., I.A.M., T.Q., T.D.E., D.Y.C., M.A.Y., S.S., C.A.), Massachusetts General Hospital, Harvard Medical School, Boston.
Stroke
|March 6, 2023
Summary
Optogenetically induced spreading depolarizations (SDs) did not worsen stroke outcomes in mice. These findings challenge the idea that SDs causally link to infarct expansion in focal cerebral ischemia.
Area of Science:
- Neuroscience
- Cerebrovascular Research
- Optogenetics
Background:
- Spreading depolarizations (SDs) are implicated in worsening outcomes in focal cerebral ischemia.
- Previous studies used invasive methods to induce SDs, potentially confounding results.
- The role of SDs in infarct expansion remains unclear due to methodological limitations.
Purpose of the Study:
- To investigate whether noninjuriously induced SDs exacerbate infarct volumes in focal cerebral ischemia.
- To determine the causal link between SDs and infarct expansion using optogenetics.
Main Methods:
- Transgenic mice (Thy1-ChR2-YFP) received optogenetic SD induction during middle cerebral artery occlusion.
- Laser speckle imaging monitored cerebral blood flow.
- Infarct volumes were quantified 24-48 hours post-occlusion.
Main Results:
- Optogenetic SD induction did not alter infarct volumes compared to controls.
- Increased SD frequency did not correlate with larger infarcts.
- Optogenetic stimulation did not affect peri-infarct perfusion.
Conclusions:
- Noninjurious optogenetic induction of SDs does not worsen tissue outcomes in focal cerebral ischemia.
- The findings necessitate a reevaluation of the causal relationship between SDs and infarct expansion.
- Optogenetics provides a novel, non-invasive method to study SDs in stroke models.
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