scholarly journals Pathophysiology of migraine: From molecular to personalized medicine

2013 ◽  
Vol 66 (1-2) ◽  
pp. 53-57 ◽  
Author(s):  
Zvezdana Kojic ◽  
Dobrica Stojanovic
Keyword(s):  
Personalized Medicine ◽  
Cortical Spreading Depression ◽  
Migraine Headache ◽  
Spreading Depression ◽  
Occipital Lobe ◽  
Peripheral Sensitization ◽  
Cutaneous Allodynia ◽  
Migraine Pathophysiology ◽  
Hereditary Nature ◽  
The Brain

Introduction. Understanding of migraine pathophysiology has substantially improved over the last two decades. As a result, migraine is now mainly considered to be a disorder of the brain, rather than one of the vasculature or the meninges. Pathophysiology. Although it remains speculative how exactly they relate to each other, the following three processes are important in migraine: 1. Cortical spreading depression is a wave of intense depolarization, it starts in the occipital lobe, propagates through the brain and is followed by a period of suppressed activity. 2. Activation of the trigemonovascular system causes the release of neuropeptides (e.g. calcitonin gene-related peptide, substance P) from the peripheral trigeminal nerve endings. These neuropeptides are thouglt to play a role in causing and maintaing headache. 3. Sensitization of peripheral and central brain areas, it is thought that pulsating quality of migraine headache is caused by a process of peripheral sensitization. Cutaneous allodynia is a marker of central sensitization. Link between Aura and Headache. The view that the aura is caused by cortical spreading depression has become generally accepted, and the same is true for the view that activation of the trigemonovascular system underlies migraine headache. However, the relationship between the aura and the activation of the trigemonovascular system and the start of headache remains elusive. Genetics of Migraine. One of the most important aspects of the pathophysiology of migraine is the hereditary nature of the disorder. Conclusion. Identification of polymorphisms and genetic biomarkers should help us to understand migraine pathophysiology better and thus enable the development of specific, effective ?individually-tailored treatment? for each particular migraine patient (personalized medicine).

The use of cortical spreading depression for studying the brain actions of antioxidants

2012 ◽  
Vol 15 (3) ◽  
pp. 111-119 ◽  
Author(s):  
R C A Guedes ◽  
Ricardo Abadie-Guedes ◽  
Ranilson de Souza Bezerra
Keyword(s):  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
The Brain

scholarly journals Assessment of neurovascular coupling and cortical spreading depression in mixed mouse models of atherosclerosis and Alzheimer’s disease

eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
Osman Shabir ◽  
Ben Pendry ◽  
Llywelyn Lee ◽  
Beth Eyre ◽  
Paul S Sharp ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cortical Spreading Depression ◽  
Mixed Model ◽  
Spreading Depression ◽  
Neurovascular Coupling ◽  
Cardiovascular Comorbidities ◽  
Neurological Conditions ◽  
Electrode Insertion ◽  
The Brain

Neurovascular coupling is a critical brain mechanism whereby changes to blood flow accompany localised neural activity. The breakdown of neurovascular coupling is linked to the development and progression of several neurological conditions including dementia. In this study, we examined cortical haemodynamics in mouse preparations that modelled Alzheimer’s disease (J20-AD) and atherosclerosis (PCSK9-ATH) between 9 and 12 m of age. We report novel findings with atherosclerosis where neurovascular decline is characterised by significantly reduced blood volume, altered levels of oxyhaemoglobin and deoxyhaemoglobin, in addition to global neuroinflammation. In the comorbid mixed model (J20-PCSK9-MIX), we report a 3 x increase in hippocampal amyloid-beta plaques. A key finding was that cortical spreading depression (CSD) due to electrode insertion into the brain was worse in the diseased animals and led to a prolonged period of hypoxia. These findings suggest that systemic atherosclerosis can be detrimental to neurovascular health and that having cardiovascular comorbidities can exacerbate pre-existing Alzheimer’s-related amyloid-plaques.

Are Cortical Spreading Depression and Headache in Migraine Causally Linked?

Cephalalgia ◽  
2009 ◽  
Vol 29 (2) ◽  
pp. 244-249 ◽  
Author(s):  
J Wolthausen ◽  
S Sternberg ◽  
C Gerloff ◽  
A May
Keyword(s):  
Migraine With Aura ◽  
Cortical Spreading Depression ◽  
Migraine Headache ◽  
Spreading Depression ◽  
International Headache Society ◽  
Neuronal Process ◽  
The Third ◽  
The Past ◽  
Migraine Headaches

During the past few decades, much controversy has surrounded the pathophysiology of migraine. Cortical spreading depression (CSD) is widely accepted as the neuronal process underlying visual auras. It has been proposed that CSD can also cause the headaches, at least in migraine with aura. We describe three patients, each fulfilling the International Headache Society criteria for migraine with aura, who suffered from headaches 6–10 days per month. Two patients were treated with flunarizine and the third patient with topiramate for the duration of 4 months. All patients reported that aura symptoms resolved completely, whereas the migraine headache attacks persisted or even increased. These observations question the theory that CSD (silent or not) is a prerequisite for migraine headaches.

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.

Migraine Pathophysiology and its Clinical Implications

Cephalalgia ◽  
2004 ◽  
Vol 24 (2_suppl) ◽  
pp. 2-7 ◽  
Author(s):  
SD Silberstein
Keyword(s):  
Neurogenic Inflammation ◽  
Spreading Depression ◽  
Acute Attack ◽  
Clinical Implications ◽  
Trigeminal Nucleus ◽  
Visual Aura ◽  
Parasympathetic System ◽  
Integrated Theory ◽  
Cutaneous Allodynia ◽  
Migraine Pathophysiology

The vascular hypothesis of migraine has now been superseded by a more integrated theory that involves both vascular and neuronal components. It has been demonstrated that the visual aura experienced by some migraineurs arises from cortical spreading depression, and that this neuronal event may also activate perivascular nerve afferents, leading to vasodilation and neurogenic inflammation of the meningeal blood vessels and, thus, throbbing pain. The involvement of the parasympathetic system supplying the meninges also causes increased vasodilation and pain. As an acute attack progresses, sensory neurones in the trigeminal nucleus caudalis become sensitized, resulting in the phenomenon of cutaneous allodynia. Triptans may act at several points during the progression of a migraine attack. However, the development of central sensitization impacts upon the effectiveness of triptan therapy.

scholarly journals Evaluation of cutaneous allodynia following induction of cortical spreading depression in freely moving rats

Cephalalgia ◽  
2011 ◽  
Vol 31 (10) ◽  
pp. 1090-1100 ◽  
Author(s):  
Beatriz Fioravanti ◽  
Aimen Kasasbeh ◽  
Rebecca Edelmayer ◽  
David P Skinner Jr ◽  
Jed A Hartings ◽  
...  
Keyword(s):  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Occipital Cortex ◽  
Underlying Mechanism ◽  
Bioelectrical Activity ◽  
Freely Moving Rats ◽  
Cutaneous Allodynia ◽  
The Face ◽  
Freely Moving ◽  
Sustained Activation

Background: Cortical spreading depression (CSD) is a wave of depolarization followed by depression of bioelectrical activity that slowly propagates through the cortex. CSD is believed to be the underlying mechanism of aura in migraine; however, whether CSD can elicit pain associated with migraine headache is unclear. Methods: Awake, freely moving rats were monitored for both CSD events and behavioral responses resulting from dural-cortical pinprick and/or KCl injection to the occipital cortex. Results: We observed tactile allodynia of the face and hindpaws, as well as enhanced Fos expression within the trigeminal nucleus caudalis (TNC) following CSD induced by KCl injection into the cortex, but not by pinprick. Application of KCl onto the dura elicited cutaneous allodynia and increased Fos staining in the TNC but did not elicit CSD events. Conclusions: These data suggest that sustained activation of trigeminal afferents that may be required to establish cutaneous allodynia may not occur following CSD events in normal animals.

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