Migraine, aura, and cortical spreading depression: Why are we still talking about it?

2001 ◽  
Vol 49 (1) ◽  
pp. 4-6 ◽  
Author(s):  
Peter James Goadsby
Keyword(s):  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Migraine Aura

Migraine

2020 ◽  
pp. 213-224
Author(s):  
Julio R Vieira ◽  
Richard B Lipton
Keyword(s):  
Chronic Migraine ◽  
Migraine With Aura ◽  
Cortical Spreading Depression ◽  
Migraine Without Aura ◽  
Spreading Depression ◽  
Headache Frequency ◽  
Motor Symptoms ◽  
Migraine Aura ◽  
Younger Age ◽  
Psychiatric Conditions

This chapter examines migraine. The incidence of migraine varies depending on multiple aspects, including age, sex, and the presence of aura. At an earlier age (younger than age ten), migraine initially affects more boys than girls, with migraine with aura (MA) occurring at a younger age than migraine without aura (MO). Later in life, when puberty starts, this relationship changes and it becomes more common in women than men. Migraine aura are focal neurological symptoms that typically occur prior to the onset of a headache due to a phenomenon called cortical spreading depression. The prevalence of migraine with aura vary between visual, sensory, or motor symptoms. It can also present as diplopia, slurred speech, aphasia, dizziness, vertigo, and hemiparesis. Moreover, the prevalence of migraine varies according to headache frequency. The chapter then looks at chronic migraine and menstrual migraine. It also explores several comorbidities associated with migraine, including many neurologic, medical, and psychiatric conditions.

scholarly journals High-mobility group box 1 is an important mediator of microglial activation induced by cortical spreading depression

2016 ◽  
Vol 37 (3) ◽  
pp. 890-901 ◽  
Author(s):  
Tsubasa Takizawa ◽  
Mamoru Shibata ◽  
Yohei Kayama ◽  
Toshihiko Shimizu ◽  
Haruki Toriumi ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Cortical Spreading Depression ◽  
Microglial Activation ◽  
Spreading Depression ◽  
High Mobility ◽  
High Mobility Group ◽  
Migraine Aura ◽  
Double Knockout ◽  
Activated Microglia ◽  
Important Mediator

Single episodes of cortical spreading depression (CSD) are believed to cause typical migraine aura, whereas clusters of spreading depolarizations have been observed in cerebral ischemia and subarachnoid hemorrhage. We recently demonstrated that the release of high-mobility group box 1 (HMGB1) from cortical neurons after CSD in a rodent model is dependent on the number of CSD episodes, such that only multiple CSD episodes can induce significant HMGB1 release. Here, we report that only multiple CSD inductions caused microglial hypertrophy (activation) accompanied by a greater impact on the transcription activity of the HMGB1 receptor genes, TLR2 and TLR4, while the total number of cortical microglia was not affected. Both an HMGB1-neurtalizing antibody and the HMGB1 inhibitor glycyrrhizin abrogated multiple CSD-induced microglial hypertrophy. Moreover, multiple CSD inductions failed to induce microglial hypertrophy in TLR2/4 double knockout mice. These results strongly implicate the HMGB1–TLR2/4 axis in the activation of microglia following multiple CSD inductions. Increased expression of the lysosomal acid hydrolase cathepsin D was detected in activated microglia by immunostaining, suggesting that lysosomal phagocytic activity may be enhanced in multiple CSD-activated microglia.

Oxcarbazepine does not suppress cortical spreading depression

Cephalalgia ◽  
2010 ◽  
Vol 31 (5) ◽  
pp. 537-542 ◽  
Author(s):  
Ulrike Hoffmann ◽  
Ergin Dileköz ◽  
Chiho Kudo ◽  
Cenk Ayata
Keyword(s):  
Single Dose ◽  
Cortical Spreading Depression ◽  
Chronic Treatment ◽  
Spreading Depression ◽  
Screening Tool ◽  
Positive Control ◽  
Migraine Prophylaxis ◽  
Migraine Aura ◽  
Predictive Utility ◽  
Prophylactic Drugs

Background: Cortical spreading depression is the electrophysiological substrate of migraine aura, and may trigger headache. Recently, chronic treatment with five migraine prophylactic drugs was shown to suppress cortical spreading depression, implicating spreading depression as a common therapeutic target in migraine prophylaxis. Materials and methods: In order to assess the negative predictive value of spreading depression susceptibility as a preclinical drug screening tool, we tested oxcarbazepine, an anti-epileptic ineffective in migraine prophylaxis. Valproate served as the positive control. Cortical spreading depression susceptibility was measured in rats using topical KCl or electrical stimulation. Results: Oxcarbazepine did not suppress spreading depression either after a single dose or after daily treatment for 5 weeks. As previously shown, valproate suppressed spreading depression susceptibility after chronic dosing, while a single dose was ineffective. Conclusions: These data provide further support for spreading depression as a relevant target in migraine prophylaxis, and demonstrate the predictive utility of employed spreading depression models.

History of migraine with aura and cortical spreading depression from 1941 and onwards

Cephalalgia ◽  
2009 ◽  
Vol 30 (7) ◽  
pp. 780-792 ◽  
Author(s):  
PC Tfelt-Hansen
Keyword(s):  
Blood Flow ◽  
Migraine With Aura ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Cerebral Arteries ◽  
Familial Hemiplegic Migraine ◽  
Migraine Aura ◽  
History Of ◽  
Dramatic Shift ◽  
The Brain

Several personal descriptions of migraine with aura from 1870 onwards reported a slow, gradual progression of symptoms. Lashley in 1941 meticulously chartered his own auras and concluded that the symptomatology reflected a cortical process progressing with a speed of 3 mm/min across the primary visual cortex. Leão described cortical spreading depression (CSD) in rabbits in 1944 and noticed its similarity to the migraine aura. Despite these scattered pieces of evidence, the prevailing theory was that the migraine aura was caused by a vasospasm and cortical ischaemia. The advent of a technique for measurements of regional cerebral blood flow (rCBF) in 1974 made it possible to detect spreading oligaemia during migraine aura. Between 1981 and 1990 a series of studies of rCBF during migraine attacks showed reduced brain blood flow posteriorly spreading slowly and contiguously anteriorly and crossing borders of supply of major cerebral arteries. These observations refuted the ischaemic hypothesis. The human studies showed initial hyperaemia followed by prolonged hypoperfusion. The relation between aura and CSD was known to cause short-lasting, and therefore not obvious vasodilation and it was considerably strengthened by the demonstration of a long-lasting oligaemia in rats in the wake of CSD. In the primates CSD is not easily elicited, but it has in recent years been clearly demonstrated in patients with brain trauma and stroke. Finally, mutations for familial hemiplegic migraine have been expressed in mice and lower the threshold for CSD. The seminal papers on rCBF and CSD published in the 1980s caused a dramatic shift in our concepts of migraine aura. They moved attention from ischaemia to CSD and thereby to the brain itself, and paved the way for subsequent discoveries of brainstem mechanisms.

Does Metoprolol Inhibit the Cortical Spreading Depression? Acute Effects of Systematic Metropol on CSD in Rats

Cephalalgia ◽  
2007 ◽  
Vol 27 (9) ◽  
pp. 1010-1013 ◽  
Author(s):  
M Alemdar ◽  
Ö Akman ◽  
HM Selekler ◽  
SŞ Komsuoğlu ◽  
N Ateş
Keyword(s):  
Dura Mater ◽  
Cortical Spreading Depression ◽  
Wistar Rats ◽  
Spreading Depression ◽  
Migraine Prophylaxis ◽  
Migraine Aura ◽  
Direct Effects ◽  
Acute Effects ◽  
Before And After ◽  
Induction Model

Cortical spreading depression (CSD) is supposed to be the underlying biological basis of the migraine aura. Metoprolol was proven to be effective in migraine prophylaxis in clinical trials, but its mechanism of action has not been clarified yet. We studied direct effects of metoprolol on a continuous CSD induction model in rats. Six adult Wistar rats were anaesthetized with intraperitoneal thiopental (50 mg/kg). CSD was induced with application of 1 M KCL through a burr hole into the left frontal dura-mater, and recorded by an Ag/AgCl DC electrode on the left parietal dura-mater. After a basal recording of CSD induction during the first 40-min period, metoprolol (5 mg/kg) was infused within 4 min. Then DC recordings were maintained for a further 120 min. Any significant differences in total number and duration of CSDs before and after metoprolol administration were not detected. This study suggests that the mode of action of metoprolol in prophylaxis is not via direct CSD inhibition.

scholarly journals Gabapentin Suppresses Cortical Spreading Depression Susceptibility

2010 ◽  
Vol 30 (9) ◽  
pp. 1588-1592 ◽  
Author(s):  
Ulrike Hoffmann ◽  
Ergin Dileköz ◽  
Chiho Kudo ◽  
Cenk Ayata
Keyword(s):  
Brain Injury ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Tolerability Profile ◽  
Affinity Binding ◽  
Migraine Aura ◽  
High Affinity Binding ◽  
High Affinity ◽  
Depolarization Wave ◽  
Favorable Safety

Cortical spreading depression (CSD) is an intense depolarization wave implicated in the pathophysiology of brain injury states and migraine aura. As Cav2.1 channels modulate CSD susceptibility, we tested gabapentin, which inhibits Cav2.1 through high-affinity binding to its α2δ subunit, on CSD susceptibility in anesthetized rats. Gabapentin, 100 or 200 mg/kg, elevated the electrical threshold for CSD and diminished recurrent CSDs evoked by topical KCl, when administered 1 hour before testing. With its favorable safety and tolerability profile, gabapentin may have a role in suppression of injury depolarizations in stroke, intracranial hemorrhage, and traumatic brain injury.

scholarly journals Estrogen-dependent effects of 5-hydroxytryptophan on cortical spreading depression in rat: Modelling the serotonin-ovarian hormone interaction in migraine aura

Cephalalgia ◽  
2017 ◽  
Vol 38 (3) ◽  
pp. 427-436 ◽  
Author(s):  
Virginie Chauvel ◽  
Sylvie Multon ◽  
Jean Schoenen
Keyword(s):  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Cortical Excitability ◽  
Ovarian Hormones ◽  
Inhibitory Effect ◽  
Female Rats ◽  
Cycle Phase ◽  
Migraine Aura ◽  
Potential Efficacy ◽  
Estrogen Withdrawal

Background Cortical spreading depression (CSD) is the likely culprit of the migraine aura. Migraine is sexually dimorphic and thought to be a “low 5-HT” condition. We sought to decipher the interrelation between serotonin, ovarian hormones and cortical excitability in a model of migraine aura. Methods Occipital KCl-induced CSDs were recorded for one hour at parieto-occipital and frontal levels in adult male (n = 16) and female rats (n = 64) one hour after intraperitoneal (i.p.) injection of 5-hydroxytryptophan (5-HTP) or NaCl. Sixty-five oophorectomized females were treated with estradiol- (E2) or cholesterol- (Chol) filled capsules. Two weeks later we recorded CSDs after 5-HTP/NaCl injections before or 20 hours after capsule removal. Results 5-HTP had no effect in males, but decreased CSD frequency in cycling females, significantly so during estrus, at parieto-occipital (−3.5CSD/h, p < 0.001) and frontal levels (−2.5CSD/h, p = 0.014). In oophorectomized rats, CSD susceptibility increased during E2 treatment at both recording sites (+5CSD/h, p = 0.001 and +3CSD/h, p < 0.01), but decreased promptly after E2 withdrawal (−4.7CSD/h, p < 0.001 and −1.7CSD/h, p = 0.094). The CSD inhibitory effect of 5-HTP was significant only in E2-treated rats (−3.4CSD/h, p = 0.006 and −1.8CSD/h, p = 0.029). Neither the estrous cycle phase, nor E2 or 5-HTP treatments significantly modified CSD propagation velocity. Conclusion 5-HTP decreases CSD occurrence in the presence of ovarian hormones, suggesting its potential efficacy in migraine with aura prophylaxis in females. Elevated E2 levels increase CSD susceptibility, while estrogen withdrawal decreases CSD. In a translational perspective, these findings may explain why migraine auras can appear during pregnancy and why menstrual-related migraine attacks are rarely associated with an aura.

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