Female-selective mechanisms promoting migraine

The Journal of Headache and Pain, Год журнала: 2024, Номер 25(1)

Опубликована: Апрель 24, 2024

Sexual dimorphism has been revealed for many neurological disorders including chronic pain. Prelicinal studies and post-mortem analyses from male female human donors reveal sexual of nociceptors at transcript, protein functional levels suggesting different mechanisms that may promote pain in men women. Migraine is a common female-prevalent disorder characterized by painful debilitating headache. Prolactin neurohormone circulates higher females implicated clinically migraine. sensitizes sensory neurons mice, non-human primates humans revealing female-selective mechanism conserved evolutionarily likely translationally relevant. produces migraine-like behaviors rodents enhances the release calcitonin gene-related peptide (CGRP), neurotransmitter causal promoting migraine patients. CGRP, like prolactin, behaviors. Consistent with these observations, publicly available clinical data indicate small molecule CGRP-receptor antagonists are preferentially effective treatment acute therapy Collectively, observations support conclusion qualitative sex differences providing opportunity to tailor therapies based on patient improved outcomes. Additionally, should be considered design trials as well reassessment past warranted.

Язык: Английский

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Similarities in the Electrographic Patterns of Delayed Cerebral Infarction and Brain Death After Aneurysmal and Traumatic Subarachnoid Hemorrhage

Translational Stroke Research, Год журнала: 2024, Номер unknown

Опубликована: Фев. 23, 2024

Abstract While subarachnoid hemorrhage is the second most common hemorrhagic stroke in epidemiologic studies, recent DISCHARGE-1 trial has shown that reality, three-quarters of focal brain damage after ischemic. Two-fifths these ischemic infarctions occur early and three-fifths are delayed. The vast majority cortical infarcts whose pathomorphology corresponds to anemic infarcts. Therefore, we propose this review as an ischemic-hemorrhagic rather a third, separate entity addition purely or strokes. Cumulative damage, determined by neuroimaging first 2 weeks, strongest known predictor patient outcome half year initial hemorrhage. Because unique ability implant neuromonitoring probes at surface before onset perform longitudinal MRI scans stroke, delayed cerebral ischemia currently variant humans pathophysiological details far best characterized. Optoelectrodes located directly over newly developing have that, mechanistic correlates infarct development, spreading depolarizations trigger (1) ischemia, (2) severe hypoxia, (3) persistent activity depression, (4) transition from clustered negative ultraslow potential. Furthermore, traumatic injury third etiologies death during continued systemic circulation. Here, use examples illustrate although cascades associated with global, they closely resemble local development

Язык: Английский

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Acute-Phase Recording of the Spreading Depolarization Continuum in Aged Nonhuman Primates During Focal Ischemic Stroke

Stroke, Год журнала: 2025, Номер unknown

Опубликована: Фев. 27, 2025

BACKGROUND: Decades of experimental and clinical data revealed that spreading depolarizations (SDs) play a central causal role in the development cortical lesions after acute brain injury. However, documentation events at onset focal ischemic stroke during initial phase injury is lacking because electroencephalography monitoring SD typically starts hours or days later. Here, we used nonhuman primates to map electrophysiological pathology through stroke’s stage. METHODS: Craniotomies were performed over both hemispheres on 4 male 1 female nemestrina rhesus macaques aged 23 years 32 years. Subdural electrode arrays placed bilaterally middle cerebral artery territory, recording from 24 electrodes cm apart left cortex 7 right. After 30 minutes baseline monitoring, and, some cases, also internal carotid anterior arteries permanently occluded with aneurysmal clips. RESULTS: Repetitive SDs occurred next 3 hours, followed by terminal euthanasia. No epileptiform activity was observed any 5 animals. Nonspreading electrical silence developed core within seconds onset, SD-initiated negative ultraslow potential several minutes. These defined led histologically confirmed cell damage. Initial subsequent transient caused depression spontaneous normally perfused surrounding without signs histological Cardiocirculatory arrest end experiments first induced nonspreading eventually, potential, which indicated death. CONCLUSIONS: Results gyrencephalic hold significant implications for understanding translation diagnosis pathologies manifested continuum.

Язык: Английский

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Molecular, Pathological, Clinical, and Therapeutic Aspects of Perihematomal Edema in Different Stages of Intracerebral Hemorrhage

Oxidative Medicine and Cellular Longevity, Год журнала: 2022, Номер 2022, С. 1 - 38

Опубликована: Сен. 17, 2022

Acute intracerebral hemorrhage (ICH) is a devastating type of stroke worldwide. Neuronal destruction involved in the brain damage process caused by ICH includes primary injury formed mass effect hematoma and secondary induced degradation products blood clot. Additionally, factors coagulation cascade complement activation also contribute to promoting disruption blood-brain barrier neuronal cell degeneration enhancing inflammatory response, oxidative stress, etc. Although treatment options for direct are limited, various strategies have been proposed treat post-ICH. Perihematomal edema (PHE) potential surrogate marker may poor outcomes after ICH. Therefore, it essential investigate underlying pathological mechanism, evolution, therapeutic PHE. Here, we review pathophysiology imaging characteristics PHE at different stages acute As illustrated preclinical clinical studies, discussed merits limitations varying quantification protocols, including absolute volume, relative extension distance calculated with images other techniques. Importantly, this summarizes that affect focusing on traditional variables, cerebral venous drainage system, lymphatic system. Finally, facilitate translational research, analyze why relationship between functional outcome currently controversial. We emphasize promising approaches modulate multiple targets alleviate promote neurologic recovery

Язык: Английский

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A cold and quiet brain: mechanisms of insect CNS arrest at low temperatures

Current Opinion in Insect Science, Год журнала: 2023, Номер 58, С. 101055 - 101055

Опубликована: Май 16, 2023

Язык: Английский

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Spreading depolarization and angiographic spasm are separate mediators of delayed infarcts

Brain Communications, Год журнала: 2023, Номер 5(2)

Опубликована: Март 2, 2023

In DISCHARGE-1, a recent Phase III diagnostic trial in aneurysmal subarachnoid haemorrhage patients, spreading depolarization variables were found to be an independent real-time biomarker of delayed cerebral ischaemia. We here investigated based on prospectively collected data from DISCHARGE-1 whether infarcts the anterior, middle, or posterior artery territories correlate with (i) extravascular blood volumes; (ii) predefined variables, proximal vasospasm assessed by either (iii) digital subtraction angiography (iv) transcranial Doppler-sonography; and depolarizations and/or are mediators between infarcts. Relationships variable groups analysed using Spearman correlations 136 patients. Thereafter, principal component analyses performed for each group. Obtained components included path models priori defined structure. first model, we only as our primary interest was investigate depolarizations. Standardised coefficients 0.22 bloodcomponent depolarizationcomponent (P = 0.010); 0.44 infarct volume < 0.001); but 0.07 direct infarctcomponent 0.36). Thus, role mediator confirmed. analysis volume, intraventricular not represented component. Therefore, correlation analyses, also constructed another model without second extrinsic variable. two paths, one (subarachnoid) (path 0.23, P 0.03; 0.29, 0.002), angiographic vasospasmcomponent 0.24, 0.35, 0.001). Human autopsy studies shaped hypothesis that clots cortex surface suffice cause beneath clots. Experimentally, clot-released factors induce cortical trigger neuronal cytotoxic oedema The statistical supports this pathogenetic concept. did find triggers depolarizations, contributed volume. This could possibly result enhancement depolarization-induced ischaemia reduced upstream supply.

Язык: Английский

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Diversity of cortical activity changes beyond depression during Spreading Depolarizations

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Ноя. 25, 2023

Spreading depolarizations (SDs) are classically thought to be associated with spreading depression of cortical activity. Here, we found that SDs in patients subarachnoid hemorrhage produce variable, ranging from booming, changes electrocorticographic activity, especially the delta frequency band. In rats, activity was characteristic high-potassium-induced full SDs, whereas partial superficial caused either little change or a boom at vertex, supported by volume conduction signals spared generators deep layers. Partial also moderate neuronal depolarization and sustained excitation, organized gamma oscillations narrow sub-SD zone. Thus, our study challenges concept homology between showing surface different layers depending on depth SD penetration.

Язык: Английский

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Eighteen-hour inhibitory effect of s-ketamine on potassium- and ischemia-induced spreading depolarizations in the gyrencephalic swine brain

Neuropharmacology, Год журнала: 2022, Номер 216, С. 109176 - 109176

Опубликована: Июль 5, 2022

Язык: Английский

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Spreading depolarization causes reversible neuronal mitochondria fragmentation and swelling in healthy, normally perfused neocortex

Journal of Cerebral Blood Flow & Metabolism, Год журнала: 2024, Номер 44(12), С. 1561 - 1579

Опубликована: Июль 25, 2024

Mitochondrial function is tightly linked to morphology, and fragmentation of dendritic mitochondria during noxious conditions suggests loss function. In the normoxic cortex, spreading depolarization (SD) a phenomenon underlying migraine aura. It unknown whether structure affected by SD. vivo two-photon imaging followed quantitative serial section electron microscopy (ssEM) was used monitor in cortex urethane-anesthetized mature male female mice after SD initiated focal KCl microinjection. Structural dynamics dendrites their were visualized transfecting excitatory, glutamatergic neurons somatosensory with bicistronic AAV, which induced tdTomoto labeling neuronal cytoplasm roGFP. Normoxic triggered rapidly reversible alongside beading; however, took significantly longer recover. Several rounds resulted transient mitochondrial beading without accumulating injury, as both recovered. SsEM corroborated SD-elicited swelling transformation filamentous network into shorter, swollen tubular, globular structures. Our results revealed SD-induced disruption that might impact bioenergetics

Язык: Английский

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The evolving concept of multimorbidity and migraine

Handbook of clinical neurology, Год журнала: 2024, Номер unknown, С. 535 - 566

Опубликована: Янв. 1, 2024

Язык: Английский

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