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Cortical spreading depression causes a long-lasting decrease in cerebral blood flow and induces tolerance to
Tatsuo Otori1, Joel H Greenberg, Frank A Welsh
1Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia 19104-6070, USA.
Summary
Cortical spreading depression (CSD) preconditioning reduces brain damage from permanent stroke by preserving blood flow. This neuroprotective effect, linked to reduced baseline cerebral blood flow, offers a new strategy for stroke tolerance.
Area of Science:
- Neuroscience
- Cerebrovascular Physiology
- Ischemic Stroke Research
Background:
- Cortical spreading depression (CSD) is known to induce tolerance to transient cerebral ischemia.
- The neuroprotective mechanisms of CSD, particularly against permanent focal ischemia, require further elucidation.
Purpose of the Study:
- To investigate if CSD preconditioning confers tolerance to permanent focal cerebral ischemia.
- To determine if alterations in cerebral blood flow (CBF) mediate this potential tolerance.
Main Methods:
- Rats were preconditioned with potassium chloride to induce CSD.
- Permanent middle cerebral artery (MCA) occlusion was performed three days later.
- Cerebral blood flow was monitored using laser Doppler flowmetry (LDF) and [14C]iodoantipyrine.
Main Results:
- CSD preconditioning significantly reduced infarct volume (hemispheric and neocortical) after MCA occlusion.
- CSD preconditioning preserved relative CBF during the ischemic period.
- CSD induced a long-lasting decrease in baseline CBF, suggesting reduced metabolic rate.
Conclusions:
- CSD preconditioning provides neuroprotection against permanent focal ischemia.
- Preserved CBF during ischemia and reduced baseline CBF likely contribute to CSD-induced ischemic tolerance.
- Reduced metabolic rate may be a key factor in CSD-mediated tolerance to stroke.