Vascular pathology of large cerebral arteries in experimental subarachnoid hemorrhage: Vasoconstriction, functional CGRP depletion and maintained CGRP sensitivity

Johansson, Sara Ellinor; Abdolalizadeh, Bahareh; Sheykhzade, Majid; Edvinsson, Lars; Sams, Anette

doi:10.1016/j.ejphar.2019.01.007

Cited by 17 publications

(10 citation statements)

References 58 publications

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“…In fact, endogenous CGRP is protective against neuronal damage in the setting of acute or chronic stroke, as suggested by experiments using CGRP knockout mice. CGRP has been shown to reduce infarct size [83], and CGRP is protective against cerebral vasospasm in the setting of subarachnoid hemorrhage [84]. CGRP might also be protective in individuals with chronic bilateral carotid stenosis by reducing subsequent neuronal injury and cognitive impairment [83].…”

Section: Mechanisms Underlying the Migraine Sd And Stroke Associationmentioning

confidence: 99%

Aura and Stroke: relationship and what we have learnt from preclinical models

Yemişçi

Eikermann-Haerter

2019

J Headache Pain

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BackgroundPopulation-based studies have highlighted a close relationship between migraine and stroke. Migraine, especially with aura, is a risk factor for both ischemic and hemorrhagic stroke. Interestingly, stroke risk is highest for migraineurs who are young and otherwise healthy.Main bodyPreclinical models have provided us with possible mechanisms to explain the increased vulnerability of migraineurs’ brains towards ischemia and suggest a key role for enhanced cerebral excitability and increased incidence of microembolic events. Spreading depolarization (SD), a slowly propagating wave of neuronal depolarization, is the electrophysiologic event underlying migraine aura and a known headache trigger. Increased SD susceptibility has been demonstrated in migraine animal models, including transgenic mice carrying human mutations for the migraine-associated syndrome CADASIL and familial hemiplegic migraine (type 1 and 2). Upon experimentally induced SD, these mice develop aura-like neurological symptoms, akin to patients with the respective mutations. Migraine mutant mice also exhibit an increased frequency of ischemia-triggered SDs upon experimental stroke, associated with accelerated infarct growth and worse outcomes. The severe stroke phenotype can be explained by SD-related downstream events that exacerbate the metabolic mismatch, including pericyte contraction and neuroglial inflammation. Pharmacological suppression of the genetically enhanced SD susceptibility normalizes the stroke phenotype in familial hemiplegic migraine mutant mice. Recent epidemiologic and imaging studies suggest that these preclinical findings can be extrapolated to migraine patients. Migraine patients are at risk for particularly cardioembolic stroke. At the same time, studies suggest an increased incidence of coagulopathy, atrial fibrillation and patent foramen ovale among migraineurs, providing a possible path for microembolic induction of SD and, in rare instances, stroke in hyperexcitable brains. Indeed, recent imaging studies document an accelerated infarct progression with only little potentially salvageable brain tissue in acute stroke patients with a migraine history, suggesting an increased vulnerability towards cerebral ischemia.ConclusionPreclinical models suggest a key role for enhanced SD susceptibility and microembolization to explain both the occurrence of migraine attacks and the increased stroke risk in migraineurs. Therapeutic targeting of SD and microembolic events, or potential causes thereof, will be promising for treatment of aura and may also prevent ischemic infarction in vulnerable brains.

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Section: Mechanisms Underlying the Migraine Sd And Stroke Associationmentioning

confidence: 99%

Aura and Stroke: relationship and what we have learnt from preclinical models

Yemişçi

Eikermann-Haerter

2019

J Headache Pain

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“…As a proof-of-concept study, we demonstrate in an animal model of SAH that CV in the ICA, one of cerebral vessels affected by SAH, was significantly improved with pTNS treatment, which may be due to the previously suggested retained vasodilatory response of cerebral vessels to CGRP after SAH. 53 The trigeminal nerve superficially innervates the skin of the face and creates viable access points along the infraorbital branch of the maxillary division for invasive and noninvasive neuromodulation. 11,[54][55][56][57][58][59][60][61][62] The maxillary division is purely sensory, working in synergy with the facial nerve (CN VII).…”

Section: Discussionmentioning

confidence: 99%

Percutaneous Trigeminal Nerve Stimulation Induces Cerebral Vasodilation in a Dose-Dependent Manner

White

Shah

et al. 2021

Neurosurg.

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BACKGROUND The trigeminal nerve directly innervates key vascular structures both centrally and peripherally. Centrally, it is known to innervate the brainstem and cavernous sinus, whereas peripherally the trigemino-cerebrovascular network innervates the majority of the cerebral vasculature. Upon stimulation, it permits direct modulation of cerebral blood flow (CBF), making the trigeminal nerve a promising target for the management of cerebral vasospasm. However, trigeminally mediated cerebral vasodilation has not been applied to the treatment of vasospasm. OBJECTIVE To determine the effect of percutaneous electrical stimulation of the infraorbital branch of the trigeminal nerve (pTNS) on the cerebral vasculature. METHODS In order to determine the stimulus-response function of pTNS on cerebral vasodilation, CBF, arterial blood pressure, cerebrovascular resistance, intracranial pressure, cerebral perfusion pressure, cerebrospinal fluid calcitonin gene-related peptide (CGRP) concentrations, and the diameter of cerebral vessels were measured in healthy and subarachnoid hemorrhage (SAH) rats. RESULTS The present study demonstrates, for the first time, that pTNS increases brain CGRP concentrations in a dose-dependent manner, thereby producing controllable cerebral vasodilation. This vasodilatory response appears to be independent of the pressor response induced by pTNS, as it is maintained even after transection of the spinal cord at the C5-C6 level and shown to be confined to the infraorbital nerve by administration of lidocaine or destroying it. Furthermore, such pTNS-induced vasodilatory response of cerebral vessels is retained after SAH-induced vasospasm. CONCLUSION Our study demonstrates that pTNS is a promising vasodilator and increases CBF, cerebral perfusion, and CGRP concentration both in normal and vasoconstrictive conditions.

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“…Studies showed that within the trigeminal ganglion, the majority of nerve cells contain CGRP (calcitonin generelated peptide receptor) and CGRP-positive fibres which surround the blood vessels in both the cranial and noncranial areas [22,23]. CGRP functions as a potent dilator of cerebral arteries and arterioles by activating adenylyl cyclase in the muscle cells [24,25]. Studies have shown the ability of CGRP to specifically relax cortical arterioles without affecting venules.…”

Section: Methodsmentioning

confidence: 99%

Migraines in childhood as a cause of headache in adulthood – how to prevent it? A literature review

Ziółkiewicz,

Jartych,

Iwanicka

et al. 2024

J Pre Clin Clin Res.

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Introduction and Objective. Migraine is the most common acute and recurrent headache in children. The pain is the result of stimulation of meningeal nociceptors. There may be a genetic predisposition to generalized neuronal hyperexcitability. Aura is caused by the cortical spreading depression (CSD).Migraines hamper daily functioning and cause adverse effects in future adult life. This review aims to introduce the most common forms and present their diagnosis and treatment methods. Review Methods. The following electronic databases were searched: Pubmed, Google Scholar using the keywords 'childhood migraine disorder', 'paediatric migraine', 'migraine in children'. Articles in English were included. Brief description of the state of knowledge. The review shows both the diagnostic modalities of migraines and the latest methods of treating and preventing migraines from developing. Summary. In the diagnosis of migraine in paediatric patients, particular importance is attached to a thorough clinical history. Paediatric patients suffering from migraine have a reduced density of grey matter in the frontal cortex. In the therapeutic process a multi-media approach, including lifestyle changes, psychoeducation and psychotherapy and pharmacotherapy, are important. Conclusions. There is a good response to OCT analgesics in children and adolescents. There are reports in the literature that migraine occurring in children becomes a risk factor for migraines in adults. Migraines in children represent a difficult disease entity, both diagnostically and therapeutically. To-date, no significant changes have been demonstrated on imaging studies in children and the symptoms themselves may be uncharacteristic. Further research is needed to consider and implement the use of new drugs.

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Vascular pathology of large cerebral arteries in experimental subarachnoid hemorrhage: Vasoconstriction, functional CGRP depletion and maintained CGRP sensitivity

Cited by 17 publications

References 58 publications

Aura and Stroke: relationship and what we have learnt from preclinical models

Aura and Stroke: relationship and what we have learnt from preclinical models

Percutaneous Trigeminal Nerve Stimulation Induces Cerebral Vasodilation in a Dose-Dependent Manner

Migraines in childhood as a cause of headache in adulthood – how to prevent it? A literature review

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