Cerveau & Psycho, Journal Year: 2024, Volume and Issue: n° 171(11), P. 6 - 7
Published: Dec. 6, 2024
The Journal of Headache and Pain, Journal Year: 2025, Volume and Issue: 26(1)
Published: April 28, 2025
Language: Английский
Citations
1
Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(18), P. 5380 - 5380
Published: Sept. 11, 2024
An increased risk of ischemic stroke in migraine with aura (MA) has been consistently demonstrated. The pathophysiology factors is not yet well understood. Several mechanisms have proposed to explain the association between MA and including decreased focal cerebral blood flow other phenomena linked cortical spreading depression (CSD) as neurovascular pathology, which appear play a key role MA. In addition genetic predisposition, classic such atrial fibrillation, emboli, migraine-associated vasculopathy, endothelial dysfunction, platelet coagulation pathway abnormalities, inflammatory examined investigated. For further clarification, distinctions made features migrainous infarctions non-migrainous among migraineurs. Furthermore, less clear when considering mixed results studying migraines without (MO) hemorrhagic people all types migraine. Translational research investigating biomarkers can help identify vascular links lead treatment developments. We performed scoping review PubMed database characterize update clinical connections stroke.
Language: Английский
Citations
4
Brain, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 17, 2025
Abstract Cortical spreading depolarization (CSD), the neurophysiological event believed to underlie aura, may trigger migraine headaches through inflammatory signaling that originates in neurons and spreads meninges via astrocytes. Increasing evidence from studies on rodents patients supports this hypothesis. The transition pro-inflammatory anti-inflammatory mechanisms is crucial for resolving inflammation. However, resolution of inflammation context CSD remains poorly understood. This study aims elucidate progression post-CSD its neurons, astrocytes, microglia mouse brains. was triggered optogenetically or by pinprick. HMGB1 release, caspase-1 activation, cell-specific activation NF-κB pairs, along with ensuing transcriptomic changes, were evaluated using immunofluorescence, Western blotting, co-immunoprecipitation, FRET analysis, transcriptomics. Our findings indicate after initial burst, release ceased, which peaked 1-hour post-CSD, diminished within 3-5 hours. suggests stimuli driving decreased hours CSD. Pro-inflammatory p65:p50 cRel:p65 detected astrocyte nuclei shortly 24 former had disappeared while latter persisted, indicating a shift activity Pathway analysis data confirmed NF-κB-related transcription astrocytes no such observed neurons. Detailed Bayesian cell proportion reconstruction revealed exhibited transcriptional changes trending towards an profile, upregulation several chemokines cytokines (e.g., TNF). play role supporting responses these mediators. genes involved chemotaxis Ccl3) spine pruning C1q) implies contribute synaptic repair, could potentially modulate meningeal nociceptor extensive endfeet syncytium abutting subarachnoid perivascular spaces although direct incomplete. nuanced understanding response CNS types highlights intricate cellular interactions Following single CSD, distinct occur microglia, responses, contributing headache initiation resolution.
Language: Английский
Citations
0
The Journal of Headache and Pain, Journal Year: 2025, Volume and Issue: 26(1)
Published: Feb. 3, 2025
Spreading depolarization (SD) is a complex event that induces significant cellular stress in the central nervous system, leading to robust inflammatory response without causing cell death healthy tissues which may be called as neuro-parainflammation. Research has established clear link between SD and activation of pro-inflammatory pathways, particularly through release cytokines like interleukin-1β tumor necrosis factor-α, involvement mediators such cyclooxygenase-2 high mobility group box 1 (HMGB1). Mechanistically, opening pannexin-1 (Panx1) channels (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome play critical roles this process, facilitating signals can exacerbate conditions migraine. Furthermore, interplay neurons glial cells, astrocytes microglia, underscores intricate nature neuroinflammation triggered by SD. Importantly, these findings indicate processes also have systemic implications, affecting immune responses beyond system. Overall, body work highlights need for further exploration mechanisms underlying SD-induced inflammation potential therapeutic targets mitigate neuroinflammatory disorders. Inflammation extends system peripheral structures, including meninges trigeminovascular are headache initiation. Genetic factors, familial hemiplegic migraine (FHM), SD, increased susceptibility prolonged behaviors. Collectively, underscore interactions innate their relevance mechanisms, suggesting avenues intervention.
Language: Английский
Citations
0
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 8, 2025
Migraine attacks are believed to originate in the brain, but exact mechanisms by which brain generates peripheral nociceptive signals that drive migraine pain remain unclear. Sensory cortex hyperexcitability has been observed consistently across different subtypes. Astrocytes detect aberrant increases cortical activity via their Gq-coupled receptors and respond releasing gliotransmitters other factors with pro-inflammatory properties. In present study, we used a rat model investigate whether heightened astrocyte signaling is sufficient trigeminal meningeal responses linked generation of headaches. We an AAV-based chemogenetic approach allows selective activation Gq-GPCR signaling. targeted astrocytes visual as this region implicated migraine. Furthermore, meninges overlying densely innervated fibers. combined vivo single-unit recording nociceptors assess changes ongoing mechanosensitivity, along testing migraine-like behaviors. further calcitonin gene-related peptide (CGRP), using monoclonal antibody (anti-CGRP mAb), relevance discovered drives persistent discharge increased mechanosensitivity nociceptors. Cortical astrocytic also generated cephalic mechanical hypersensitivity, reduced exploratory behavior, anxiety-like behaviors Blocking suppressed astrocyte-mediated nociceptor alleviated associated migraine-related Our findings reveal previously unappreciated role for augmented triggering factor generate nociception greatly expand our understanding pathophysiology.
Language: Английский
Citations
0
The Journal of Headache and Pain, Journal Year: 2025, Volume and Issue: 26(1)
Published: Feb. 24, 2025
Transient Receptor Potential Melastatin 3 (TRPM3) channels are Ca2+ permeable ion that act as polymodal sensors of mechanical, thermal, and various chemical stimuli. TRPM3 highly expressed in the trigeminovascular system, including trigeminal neurons vasculature. Their presence dural afferents suggests they potential triggers migraine pain, which is originating from meningeal area. This area densely innervated by autonomous nerves contain major mediator calcitonin gene-related peptide (CGRP) peptidergic nerve fibers. Co-expression CGRP receptors a interplay between both signalling systems. Compared to other members TRP family, have high sensitivity sex hormones endogenous neurosteroid pregnenolone sulfate (PregS). The predominantly female estrogen progesterone, levels drop during menses, natural inhibitors channels, while PregS known agonist these channels. A decrease hormone has also been suggested trigger for attacks menstrually-related migraine. Notably, there remarkable difference TRPM3-mediated effects nociceptive In line with this, relaxation human isolated arteries induced activation greater females. Additionally, sex-dependent vasodilatory responses seem be influenced age-related hormonal changes, could contribute differences pathology. Consistent observations, sensory firing much more prominently than male mouse meninges, suggesting pain processing patients may differ. Overall, combined TRPM3-related neuronal vascular mechanisms provide possible explanation higher prevalence even severe quality narrative review summarizes recent data on roles pathophysiology, signalling, highlights prospects translational therapies targeting particular relevance women
Language: Английский
Citations
0
The Journal of Headache and Pain, Journal Year: 2025, Volume and Issue: 26(1)
Published: Feb. 26, 2025
Migraine is the second disabling neurological disorder with a high prevalence. Aura occurs in one-third of migraineurs and visual aura accounts for over 90%. Cortical spreading depression (CSD) underlies might trigger migraine headaches. Compared CSD induction by invasive electrical, chemical, or mechanical stimulation, optogenetics avoids direct influences on meninges stimulation process. However, previous optogenetic models mainly use Thy1-ChR2-YFP CaMKIIα-cre transgenic mice. They are limited when pathogenesis study requires mice to express other specific promotor, such as dopamine serotonin transporter promotor. In addition, reported behavioral paradigms were based under anesthesia. This aimed establish an CSD-induced model originating primary cortex (VISp) C57BL/6 J presented paradigm was awake condition. We performed viral transduction expression light-sensitive channelrhodopsin-2 pyramidal neurons VISp Regional cerebral blood flow (rCBF) measured laser speckle flowmetry confirm induction. The von Frey, light–dark box, elevated plus maze, open field test conducted verify migraine-related behaviors freely moving An stimulus induced typical triphasic rCBF change reduction 20%, confirming A single unilateral triggered bilateral periorbital hind-paw allodynia lasting 4–24 h. Notably, ipsilateral threshold significantly lower than contralateral at 1 It also generated photophobia anxiety persisting 24–48 Furthermore, cutaneous alleviated sumatriptan. proposes from presents detail. wild-type promising be wildly used MwA.
Language: Английский
Citations
0
Handbook of clinical neurology, Journal Year: 2025, Volume and Issue: unknown, P. 161 - 170
Published: Jan. 1, 2025
Language: Английский
Citations
0
Science, Journal Year: 2025, Volume and Issue: 388(6742), P. 96 - 104
Published: April 4, 2025
T cells have emerged as orchestrators of pain amplification, but the mechanism by which control processing is unresolved. We found that regulatory (T reg cells) could inhibit nociception through a was not dependent on their ability to regulate immune activation and tissue repair. Site-specific depletion or expansion meningeal (mT in mice led female-specific sex hormone–dependent modulation mechanical sensitivity. Specifically, mT produced endogenous opioid enkephalin exerted an antinociceptive action delta receptor expressed MrgprD + sensory neurons. Although restrains nociceptive processing, it dispensable for cell–mediated immunosuppression. Thus, our findings uncovered sexually dimorphic immunological circuit nociception, establishing sentinels homeostasis.
Language: Английский
Citations
0
The Journal of Headache and Pain, Journal Year: 2025, Volume and Issue: 26(1)
Published: April 23, 2025
Migraine is a common neurovascular disorder that remains currently untreated in half of the patients. One third migraine patients experience aura, which associated with development cortical spreading depolarization (CSD), wave involving neurons and glial cells. Cannabinoids have proven to be promising class compounds for treatment pain. In this study, we are proposing new strategy counteract CSD downstream events via multicomponent enhancement endocannabinoid system (ECS) by using AKU-005, simultaneously target several key endocannabinoids hydrolases. To end, profiled activity selective hydrolases their inhibition AKU-005 analyzed effect on an ex vivo slice model. The inhibitory profile was evaluated glycerol assay lysates from HEK293 cells expressing mouse human MAGL ABHD6. After cortex slices Wistar rats C57 BL/6 J-OlaHsd mice, were quantified mass spectrometry (LC-MS/MS), MAGL, FAAH, ABHD6 measured activity-based protein profiling (ABPP). studied live calcium imaging. Ex vivo, inhibited ABHD6, increasing 2-arachidonoylglycerol (2-AG) anandamide (AEA) levels rat under both basal conditions. showed milder effect, inhibiting only conditions 2-AG states. vitro analyses confirmed findings revealed mice cortex. previously reported as double MAGL/FAAH-inhibitor, also overexpressed little 2-AG-hydrolyzing enzyme brain. line these results, reduced rodent species, higher efficacy rats. Given distinct activities between brain areas migraine, may multiple serve efficient option aura.
Language: Английский
Citations
0