Cortical spreading depression

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Metrics details. Spreading depression SD is a slowly propagating wave of near-complete depolarization of neurons and glial cells across the cortex. SD is thought to contribute to the underlying pathophysiology of migraine aura, and possibly also an intrinsic brain activity causing migraine headache. Experimental models of SD have recapitulated multiple migraine-related phenomena and are considered highly translational. In this review, we summarize conventional and novel methods to trigger SD, with specific focus on optogenetic methods. We outline physiological triggers that might affect SD susceptibility, review a multitude of physiological, biochemical, and behavioral consequences of SD, and elaborate their relevance to migraine pathophysiology.

Cortical spreading depression

Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Cortical spreading depression CSD , a slowly propagated wave of depolarization followed by suppression of brain activity, is a remarkably complex event that involves dramatic changes in neural and vascular function. Since its original description in the s, CSD has been hypothesized to be the underlying mechanism of the migraine aura. Substantial evidence from animal models provides indirect support for this hypothesis, and studies showing that CSD is common in humans with brain injury clearly demonstrate that the phenomenon can occur in the human brain. Considerable uncertainty about the role of CSD in migraine remains, however, and key questions about how this event is initiated, how it spreads, and how it might cause migraine symptoms remain unanswered. This Review summarizes current concepts of CSD and its potential roles in migraine, and addresses ongoing studies aimed at a clearer understanding of this fundamental brain phenomenon. Cortical spreading depression CSD is a slowly propagating wave of altered brain activity that involves dramatic changes in neuronal, glial and vascular function. CSD has recently been extensively characterized in humans via recordings from the exposed brain surface in patients with brain injury. The widely accepted hypothesis that CSD is the physiological mechanism underlying the migraine aura is supported by substantial evidence from animal models, but definitive proof in patients with migraine is lacking. Studies in animals indicate that CSD can activate pain pathways, but the role of CSD as a potential trigger for migraine headache remains uncertain.

Acid-sensing ion channel 1: a novel therapeutic target for migraine with aura. There are arguments both for and against a temporal relationship between the migraine aura and headache.

Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Cortical spreading depression CSD is a self-propagating wave of cellular depolarization that has been implicated in migraine and in progressive neuronal injury after stroke and head trauma. Using two-photon microscopic NADH imaging and oxygen sensor microelectrodes in live mouse cortex, we find that CSD is linked to severe hypoxia and marked neuronal swelling that can last up to several minutes. Changes in dendritic structures and loss of spines during CSD are comparable to those during anoxic depolarization.

Metrics details. Spreading depression SD is a slowly propagating wave of neuronal and glial depolarization lasting a few minutes, that can develop within the cerebral cortex or other brain areas after electrical, mechanical or chemical depolarizing stimulations. These ionic shifts produce slow direct current DC potential shifts that can be recorded extracellularly. Moreover, CSD is associated with changes in cortical parenchymal blood flow. CSD has been shown to be a common therapeutic target for currently prescribed migraine prophylactic drugs. Yet, no effects have been observed for the antiepileptic drugs carbamazepine and oxcarbazepine, consistent with their lack of efficacy on migraine. Some molecules of interest for migraine have been tested for their effect on CSD. Specifically, blocking CSD may play an enabling role for novel benzopyran derivative tonabersat in preventing migraine with aura. Additionally, calcitonin gene-related peptide CGRP antagonists have been recently reported to inhibit CSD, suggesting the contribution of CGRP receptor activation to the initiation and maintenance of CSD not only at the classic vascular sites, but also at a central neuronal level.

Cortical spreading depression

Wannan Tang and Gry Fluge Vindedal contributed equally to this work. Looger, Erlend A. Cortical spreading depression is a slowly propagating wave of near-complete depolarization of brain cells followed by temporary suppression of neuronal activity. Accumulating evidence indicates that cortical spreading depression underlies the migraine aura and that similar waves promote tissue damage in stroke, trauma, and hemorrhage. Cortical spreading depression is characterized by neuronal swelling, profound elevation of extracellular potassium and glutamate, multiphasic blood flow changes, and drop in tissue oxygen tension. The slow speed of the cortical spreading depression wave implies that it is mediated by diffusion of a chemical substance, yet the identity of this substance and the pathway it follows are unknown. Accumulating evidence indicates that the phenomenon is associated with migraine headache, stroke, traumatic brain injury, and subarachnoid hemorrhage Takano and Nedergaard ; Dreier ; Charles and Baca However, microscopic investigation of the precise localization and timing of such events, critical for understanding the molecular basis of CSD, have been hampered by the lack of specific, sensitive, high-resolution and fast methods to detect these transients in living animals. The mice were housed on a h lighth dark cycle lights on at 8 AM , 1—4 mice per cage. All experimental groups contain at least 4 animals, which is in line with sample sizes in the literature.

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Ethics declarations Competing interests The authors declare no competing financial interests. Spreading depression of activity in cerebral cortex. SD is a validated experimental model of migraine aura. Bolay, H. J Clin Invest 21 :e Protective effect of ifenprodil against spreading depression in the mouse entorhinal cortex. J Cereb Blood Flow Metab 31 7 — Sleep deprivation, hypoglycemia, and impaired glycogen utilization are important metabolic stresses to synapses. Dreier Neurocritical Care Marchionni I, Pilati N, Forli A, Sessolo M, Tottene A, Pietrobon D Enhanced feedback inhibition due to increased recruitment of somatostatin-expressing interneurons and enhanced cortical recurrent excitation in a genetic mouse model of Migraine. B Average peak depolarization voltage peak V, left panel and duration of the depolarization at half amplitude HW duration, right panel elicited by CSD threshold KCl stimuli in control and by largely suprathreshold KCl stimuli of average duration 5.

Cortical spreading depression or CSD is an electrophysiological phenomenon affecting various perspectives of brain physiology such as ionic balance, neurotransmitter level, and blood flow in the brain.

Reprints and permissions. Download citation. Am J Physiol. Provided by the Springer Nature SharedIt content-sharing initiative. Most immediately, we need to examine 1 the extent to which CSDs that are apparently less harmful hyperemic and quick repolarization are associated with bad or good outcome and 2 the hypothesis that PIDs predict adverse outcome independent of classical risk factors. Keywords: cerebral blood flow, depolarization, energy metabolism, glutamate, neuronal injury, spreading depression. Advanced search. In addition, leading clinicians regarded CSD as irrelevant for human brain disorders including migraine based on the lack of evidence of CSD in the ECoG obtained in patients during epilepsy surgery Gloor, Hoffmann U, Ayata C Neurovascular coupling during spreading depolarizations. While there are concepts that challenge the link between SD and the headache of migraine [ 42 ], including the variable onset of headache following aura symptoms, aura without headache and several incongruent preclinical observations; the evidence for a plausible causal relationship of SD to trigeminal nociceptor activation and therefore likely pain remain convincing. Contents move to sidebar hide.