TY - JOUR
T1 - Vascular, electrophysiological, and metabolic consequences of cortical spreading depression in a mouse model of simulated neurosurgical conditions
AU - Carlson, Andrew P.
AU - Carter, Russell E.
AU - William Shuttleworth, C.
PY - 2012/4
Y1 - 2012/4
N2 - Objectives: Cortical spreading depression (CSD) is a metabolically taxing wave of cellular depolarization that propagates slowly across the brain. Though CSD is known to occur after brain injury in humans, it is unknown if CSD occurs during neurosurgical procedures. This study evaluates CSD in a mouse model of simulated neurosurgical conditions. Methods: Mice were intubated and ventilated, maintained at ~37°C, an arterial line placed to monitor mean arterial pressure and maintain pCO 2 ~30 mmHg. Mice were given simulated neuroanesthesia (fentanyl, propofol, and isofluorane). Burrholes and craniotomies were made to record the response to cortical bipolar cauterization. Separate sets of experiments (three animals each) examined electrocorticographic (ECoG) activity, optical measures of blood volume and vascular diameters (540 nm absorbance), and autofluorescence attributed to NADH (750 nm, two-photon excitation). Results: Ipsilateral cauterization invariably resulted in a propagating CSD wave identified by slow DC potential shifts (2.8±0.2 mm/minute, n = 6) and suppression of ECoG activity (range 0.5-7.3 minutes, n = 10). Each CSD was associated with an initial arteriolar constriction and decreased blood volume, followed by a longer-lasting vasodilation and increased blood volume. Tissue oxygenation, assessed indirectly by NADH imaging, was consistent with demand on oxidative metabolism following each CSD. Repetitive SDs resulted in loss of tissue autofluorescence, suggestive of tissue compromise. Conclusions: CSD is consistently elicited by simulated neurosurgical stimuli under simulated intraoperative conditions in mice. These events caused ECoG depression, transient vasoconstriction, and metabolic demand that propagated from the manipulation site. It is likely that CSD occurs during neurosurgery and may contribute to surgical brain injuries otherwise poorly explained.
AB - Objectives: Cortical spreading depression (CSD) is a metabolically taxing wave of cellular depolarization that propagates slowly across the brain. Though CSD is known to occur after brain injury in humans, it is unknown if CSD occurs during neurosurgical procedures. This study evaluates CSD in a mouse model of simulated neurosurgical conditions. Methods: Mice were intubated and ventilated, maintained at ~37°C, an arterial line placed to monitor mean arterial pressure and maintain pCO 2 ~30 mmHg. Mice were given simulated neuroanesthesia (fentanyl, propofol, and isofluorane). Burrholes and craniotomies were made to record the response to cortical bipolar cauterization. Separate sets of experiments (three animals each) examined electrocorticographic (ECoG) activity, optical measures of blood volume and vascular diameters (540 nm absorbance), and autofluorescence attributed to NADH (750 nm, two-photon excitation). Results: Ipsilateral cauterization invariably resulted in a propagating CSD wave identified by slow DC potential shifts (2.8±0.2 mm/minute, n = 6) and suppression of ECoG activity (range 0.5-7.3 minutes, n = 10). Each CSD was associated with an initial arteriolar constriction and decreased blood volume, followed by a longer-lasting vasodilation and increased blood volume. Tissue oxygenation, assessed indirectly by NADH imaging, was consistent with demand on oxidative metabolism following each CSD. Repetitive SDs resulted in loss of tissue autofluorescence, suggestive of tissue compromise. Conclusions: CSD is consistently elicited by simulated neurosurgical stimuli under simulated intraoperative conditions in mice. These events caused ECoG depression, transient vasoconstriction, and metabolic demand that propagated from the manipulation site. It is likely that CSD occurs during neurosurgery and may contribute to surgical brain injuries otherwise poorly explained.
KW - Cerebral blood flow
KW - Cortical spreading depression
KW - Leao's spreading depression
KW - Optical imaging
KW - Subarachnoid hemorrhage
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U2 - 10.1179/1743132811Y.0000000077
DO - 10.1179/1743132811Y.0000000077
M3 - Article
C2 - 22449775
AN - SCOPUS:84859298718
SN - 0161-6412
VL - 34
SP - 223
EP - 231
JO - Neurological Research
JF - Neurological Research
IS - 3
ER -