Effect of anoxia on ion distribution in the brain.

Cortical spreading depression (CSD) has been suggested to underlie migraine visual aura. However, it has been challenging to test this hypothesis in human cerebral cortex. Using high-field functional MRI with near-continuous recording during visual aura in three subjects, we observed blood oxygenation level-dependent (BOLD) signal changes that demonstrated at least eight characteristics of CSD, time-locked to percept/onset of the aura. Initially, a focal increase in BOLD signal (possibly reflecting vasodilation), developed within extrastriate cortex (area V3A). This BOLD change progressed contiguously and slowly (3.5 ± 1.1 mm/min) over occipital cortex, congruent with the retinotopy of the visual percept. Following the same retinotopic progression, the BOLD signal then diminished (possibly reflecting vasoconstriction after the initial vasodilation), as did the BOLD response to visual activation. During periods with no visual stimulation, but while the subject was experiencing scintillations, BOLD signal followed the retinotopic progression of the visual percept. These data strongly suggest that an electrophysiological event such as CSD generates the aura in human visual cortex.

/pdf/mechanisms-of-migraine-aura-revealed-by-functional-mri-in-w2d3pjfk3z.pdf

Mechanisms of migraine aura revealed by functional MRI in human visual cortex

It has been commonly assumed that calcium, which normally serves important functions as a membrane stabilizer, metabolic regulator, and sec­ ond messenger, also can mediate anoxic and toxic cell death (Schanne et aI., 1979; Farber, 1981; Trump et aI., 1981). It is then postulated that when the plasma membrane becomes unduly permeable to calcium, the free cytosolic concentration (Ca2+) rises to toxic levels. As applied to the brain, this hypothesis predicts that loss of cellular calcium ho­ meostasis underlies selective neuronal vulnerability in ischemia, hypoglycemia, and epileptic seizures (Siesj6, 1981; Meldrum, 1983; Raichle, 1983; for further literature, see Siesj6 and Wieloch, 1985; Siesj6, 1988). It should be clearly understood that ischemia, particularly if dense, causes all cells to loose their calcium homeostasis. The hypothesis predicts, therefore, that some cells are more vulner­ able than others because they have a higher density of calcium channels in their plasma membranes. Presumably, this could lead to untolerable local in­ creases in calcium concentration. In a recent extension of the calcium hypothesis, it was speculated that increased calcium cycling across ischemia-damaged membranes leads to a sustained rise in Ca2 + j and slow calcium overload of mitochondria, thereby causing delayed neuronal death (Deshpande et aI., 1987; see also Martins et aI., 1988). Dux et aI. (1987), inducing transient isch­ emia in the gerbil, recently assessed the time course of mitochondrial calcium deposits in glia cells and in pyramidal cells of the hippocampus CAl sector and

https://journals.sagepub.com/doi/pdf/10.1038/jcbfm.1989.20

Calcium fluxes, calcium antagonists, and calcium-related pathology in brain ischemia, hypoglycemia, and spreading depression: a unifying hypothesis.

Although the trigeminal nerve innervates the meninges and participates in the genesis of migraine headaches, triggering mechanisms remain controversial and poorly understood. Here we establish a link between migraine aura and headache by demonstrating that cortical spreading depression, implicated in migraine visual aura, activates trigeminovascular afferents and evokes a series of cortical meningeal and brainstem events consistent with the development of headache. Cortical spreading depression caused long-lasting blood-flow enhancement selectively within the middle meningeal artery dependent upon trigeminal and parasympathetic activation, and plasma protein leakage within the dura mater in part by a neurokinin-1-receptor mechanism. Our findings provide a neural mechanism by which extracerebral cephalic blood flow couples to brain events; this mechanism explains vasodilation during headache and links intense neurometabolic brain activity with the transmission of headache pain by the trigeminal nerve.

https://foil.bme.utexas.edu/media/papers/10.1038/nm0202-136.pdf

Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model

✓ The mechanisms that give rise to ischemic brain damage have not been definitively determined, but considerable evidence exists that three major factors are involved: increases in the intercellular cytosolic calcium concentration (Ca++i), acidosis, and production of free radicals. A nonphysiological rise in Ca++i due to a disturbed pump/leak relationship for calcium is believed to cause cell damage by overactivation of lipases and proteases and possibly also of endonucleases, and by alterations of protein phosphorylation, which secondarily affects protein synthesis and genome expression. The severity of this disturbance depends on the density of ischemia. In complete or near-complete ischemia of the cardiac arrest type, pump activity has ceased and the calcium leak is enhanced by the massive release of excitatory amino acids. As a result, multiple calcium channels are opened. This is probably the scenario in the focus of an ischemic lesion due to middle cerebral artery occlusion. Such ischemic tissues ca...

R.P. Kraio

Papers

Extracellular ionic variations during spreading depression