Initiation of spreading depression by synaptic and network hyperactivity: Insights into trigger mechanisms of migraine aura

Vinogradova, Lyudmila V.

doi:10.1177/0333102417724151

Cited by 31 publications

(24 citation statements)

References 97 publications

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“…These data, showing abnormal resting‐state visual network hyperconnectivity, may be in line with recent speculations suggesting the role of dynamic networks instabilities, in triggering CSD in patients with MwA. More specifically, synaptic drive from subcortical structures involved in sensory processing may be able to induce CSD in “hyper‐connected” cortical neurons, more susceptible to CSD initiation …”

Section: Functional Neuroimaging Investigationssupporting

confidence: 90%

Recent Insights in Migraine With Aura: A Narrative Review of Advanced Neuroimaging

et al. 2019

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Introduction Migraine is a complex neurological disorder characterized by severe headaches associated with a plethora of sensory hypersensitivity and neurovegetative symptoms. In about one‐third of the cases, a set of fully reversible focal neurological symptoms, the aura, accompanies the headache. In the last decades, advanced neuroimaging investigations allowed identification of structural, microstructural, and functional abnormalities characterizing the brain of patients with migraine with aura (MwA). However, mechanisms underlying the aura phenomena are still a matter of debate. Aims This article reviews the most significant findings from advanced neuroimaging studies in patients with MwA both to provide a unifying physiopathological model of the aura phenomena and to clarify the potential impact of advanced neuroimaging investigation in the clinical field. Methods A comprehensive review of PubMed citations was conducted by entering the key words “magnetic resonance imaging” combined with “migraine” AND “aura.” Other key words included “grey matter” OR “white matter,” “structural” OR “functional.” The only restriction was to English‐language publications. The abstracts of all articles published between 1997 and 2018 meeting these criteria were reviewed, and the full texts were examined for relevance to the topic. Conclusion Although several advanced neuroimaging studies have been conducted to investigate the neural correlates of aura phenomena, they have failed in identifying underlying pathophysiological mechanisms in their entirety. Nevertheless, functional and structural neuroimaging findings concerning the extrastriate visual cortex are characterized by a high level of reproducibility, so much so that they could be applied, in a not so far future, as diagnostic, prognostic, or therapeutic biomarkers for MwA.

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Section: Functional Neuroimaging Investigationssupporting

confidence: 90%

Recent Insights in Migraine With Aura: A Narrative Review of Advanced Neuroimaging

et al. 2019

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“…Hyperexcitability leading to synchronous neuronal activity is observed in the initial phase of CSD and is implicated in its generation (Mantegazza and Cestele, 2018;Pietrobon and Moskowitz, 2014;Vinogradova, 2018). Rhythmic activities characterized by periods of neuronal depolarization and increased synchronous excitability are observed in hippocampal and cortical brain slices, and are similar to slow oscillations observed in vivo during slow sleep and certain types of anesthesia.…”

Section: Discussionmentioning

confidence: 85%

“…Mechanisms of CSD initiation and propagation, which are characterized by different features and mechanisms, are not completely understood yet, although increased extracellular K + concentration and increased release of the excitatory neurotransmitter glutamate are important factors (Pietrobon and Moskowitz, 2014). Thus, migraine is a complex disorder, in which altered excitation-inhibition balance and hyperexcitability of cortical networks can be important pathological mechanisms (Pietrobon and Moskowitz, 2014;Vinogradova, 2018). Notably, they can have similarities with those that trigger epileptic seizures, although the exact differential mechanisms and the relationships between CSD and epileptic activity are not completely understood (Mantegazza and Cestele, 2018).…”

Section: Introductionmentioning

confidence: 99%

Cholinergic modulation inhibits cortical spreading depression in mouse neocortex through activation of muscarinic receptors and decreased excitatory/inhibitory drive

et al. 2020

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Cortical spreading depression (CSD) is a wave of transient network hyperexcitability leading to long lasting depolarization and block of firing, which initiates focally and slowly propagates in the cerebral cortex. It causes migraine aura and it has been implicated in the generation of migraine headache. Cortical excitability can be modulated by cholinergic actions, leading in neocortical slices to the generation of rhythmic synchronous activities (UP/DOWN states). We investigated the effect of cholinergic activation with the cholinomimetic agonist carbachol on CSD triggered with 130mM KCl pulse injections in acute mouse neocortical brain slices, hypothesizing that the cholinergic-induced increase of cortical network excitability during UP states could facilitate CSD. We observed instead an inhibitory effect of cholinergic activation on both initiation and propagation of CSD, through the action of muscarinic receptors. In fact, carbachol-induced CSD inhibition was blocked by atropine or by the preferential M1 muscarinic antagonist telenzepine; the preferential M1 muscarinic agonist McN-A-343 inhibited CSD similarly to carbachol, and its effect was blocked by telenzepine. Recordings of spontaneous excitatory and inhibitory post-synaptic currents in pyramidal neurons showed that McN-A-343 induced overall a decrease of the excitatory/inhibitory ratio. This inhibitory action may be targeted for novel pharmacological approaches in the treatment of migraine with muscarinic agonists.

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“…In migraine with aura, the progressive accumulation of K + to high concentration as it takes place in injured tissue is unlikely, therefore an increased sensitivity or hyperexcitability of neurons may stand in the center of SD elicitation (Vinogradova, 2018). In addition, hyperexcitablity may be relevant for ischemia-related SD, as well, since theoretically such a condition may predict SD occurrence at a lower threshold.…”

Section: Sd Elicitationmentioning

confidence: 99%

Susceptibility of the cerebral cortex to spreading depolarization in neurological disease states: The impact of aging

Hertelendy

Varga

Menyhárt

et al. 2019

Neurochemistry International

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Secondary injury following acute brain insults significantly contributes to poorer neurological outcome. The spontaneous, recurrent occurrence of spreading depolarization events (SD) has been recognized as a potent secondary injury mechanism in subarachnoid hemorrhage, malignant ischemic stroke and traumatic brain injury. In addition, SD is the underlying mechanism of the aura symptoms of migraineurs. The susceptibility of the nervous tissue to SD is subject to the metabolic status of the tissue, the ionic composition of the extracellular space, and the functional status of ion pumps, voltage-gated and other cation channels, glutamate receptors and excitatory amino acid transporters. All these mechanisms tune the excitability of the nervous tissue. Aging has also been found to alter SD susceptibility, which appears to be highest at young adulthood, and decline over the aging process. The lower susceptibility of the cerebral gray matter to SD in the old brain may be caused by the age-related impairment of mechanisms implicated in ion translocations between the intra-and extracellular compartments, glutamate signaling and surplus potassium and glutamate clearance. Even though the aging nervous tissue is thus less able to sustain SD, the consequences of SD recurrence in the old brain have proven to be graver, possibly leading to accelerated lesion maturation. Taken that recurrent SDs may pose an increased burden in the aging injured brain, the benefit of therapeutic approaches to restrict SD generation and propagation may be particularly relevant for elderly patients.

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Initiation of spreading depression by synaptic and network hyperactivity: Insights into trigger mechanisms of migraine aura

Cited by 31 publications

References 97 publications

Recent Insights in Migraine With Aura: A Narrative Review of Advanced Neuroimaging

Recent Insights in Migraine With Aura: A Narrative Review of Advanced Neuroimaging

Cholinergic modulation inhibits cortical spreading depression in mouse neocortex through activation of muscarinic receptors and decreased excitatory/inhibitory drive

Susceptibility of the cerebral cortex to spreading depolarization in neurological disease states: The impact of aging

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