Abstract Details

Title Selective Activation of Astrocytes Can Trigger Cortical Spreading Depression

Topic Headache

Presentation(s) S55 - (-)

Poster/Presentation
Number 002

Objective

Background CSD is a slowly propagated wave of electrical and vascular activity that is believed to underlie the migraine aura, and CSD is also triggered by local injury to the brain. The cellular mechanisms by which CSD could be spontaneously triggered remain poorly understood. In experimental models, CSD is commonly elicited by pinprick to the cortical surface, by application of high concentrations of KCl, or by tetanic electrical stimulation. Here, we investigated a less invasive, cell-specific method of triggering CSD.

Design/Methods The channelrhodopsin-2 (ChR2) receptor was selectively expressed in GFAP+ cells in mice. For in vitro investigations, hippocampal slices were prepared from these GFAP-ChR2 mice. For in vivo studies, mice were anesthetized, a thinned-skull cortical window was made, and a tungsten electrode and fiber optic were inserted through burr holes. For both preparations, a 473nm laser coupled to a fiber optic activated ChR2, and CSD was visualized with optical intrinsic signal imaging (OIS) and recorded as changes in local field potential.

Results In GFAP-ChR2 mice, activation of ChR2 with blue light elicited CSD, whereas the same intensity and duration of light exposure produced no CSD in wild-type littermate controls. Similarly, blue light activated spreading depression in hippocampal slices from GFAP-ChR2 mice but not from controls. The OIS characteristics of optically triggered CSD were different from those associated with KCl-evoked CSD, suggesting distinct cellular responses.

Conclusions These studies indicate that astrocytes can play a primary role in the initiation of CSD, and that CSD can be generated by a relatively non-invasive optical approach.

Authors/Disclosures
Serapio Baca, PhD PRESENTER	No disclosure on file
	No disclosure on file
Istvan Mody, PhD (Stanford Univ Sch of Medicine)	No disclosure on file
Andrew Charles, MD (UCLA Goldberg Migraine Program)	Dr. Charles has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pfizer. Dr. Charles has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Charles has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbvie. Dr. Charles has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen. Dr. Charles has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vectura. The institution of Dr. Charles has received research support from NIH. Dr. Charles has received publishing royalties from a publication relating to health care. Dr. Charles has a non-compensated relationship as a Executive Board Member with American Headache Society that is relevant to AAN interests or activities.
	No disclosure on file

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