Cortical spreading wave
Cortical spreading depression (CSD)
Also searched as Cortical spreading depression (CSD).
A slow wave of electrical depolarization crossing the cortex, followed by suppression. This is migraine aura — the zigzags and sparkles are the wave passing over the visual cortex. It then activates the trigeminal nerve system, which is how the aura phase becomes the headache phase.
In depth
Cortical spreading depression — the slow wave of neuronal silencing that opens a migraine. It is the reason migraine is classified as neurovascular rather than vascular.
What drives it
Quiets overexcitation increases it.
CSD propagates through massive glutamate release and NMDA-receptor-dependent depolarization of adjacent cortex. doi 10.1152/physrev.00027.2020 · PMC7786797
Magnesium status reduces it.
Magnesium is the physiological antagonist at the NMDA channel, which regulates neuronal excitability and CSD susceptibility. doi 10.1152/physrev.00027.2020 · PMC7786797
Mitochondrial energy reduces it.
Mitochondrial energy failure lowers the CSD threshold; riboflavin, magnesium and CoQ10 all act on mitochondrial energy production, which is the proposed basis of their prophylactic effect. doi 10.1152/physrev.00027.2020 · PMC7786797
What it drives
It reduces Barrier integrity.
Cortical spreading depression raised MMP-9 activity in the affected cortex and caused plasma protein leakage, blood-brain barrier opening and brain edema, all of which were prevented by MMP inhibition and absent in MMP-9 knockout mice, showing that CSD degrades barrier integrity. doi 10.1172/JCI21227 · PMID 15146242
It increases Neurovascular calm.
Cortical spreading depression — a slow wave of neuronal and glial depolarization followed by suppression — is the mechanism of migraine aura and is hypothesized to activate the trigeminovascular system. doi 10.1152/physrev.00027.2020 · PMC7786797
It increases Brain inflammation.
CSD opens neuronal pannexin-1 channels and activates caspase-1, releasing pro-inflammatory mediators that drive parenchymal and meningeal inflammation. doi 10.1152/physrev.00027.2020 · PMC7786797
It increases The Third Alarm Bell.
Cortical spreading depression activates the trigeminovascular system, releasing the neuropeptides that mediate the attack, PACAP-38 among them. doi 10.1093/brain/awn307 · PMC10994530
It increases Trigeminal nerve pathway.
Cortical spreading depression activates the trigeminovascular system, linking the aura phase to the headache phase. doi 10.1177/03331024251355944 · PMC5567577
It increases Neuronal overexcitation.
Cortical spreading depression travels as a wave of mass glutamate release and NMDA-dependent depolarization, carrying the excitotoxic load across adjacent cortex. doi 10.1186/s40035-021-00278-7 · PMC8788129
Blends that modulate it
Each blend page names this pathway and carries the study behind its claim.
See it on the map
Open the causal map to follow this pathway upstream and downstream, arrow by arrow, each with its study.