5,687 results on '"cortical spreading depression"'
Search Results
2. Aura phenomenon: a proposal for an etiology-based clinical classification.
- Author
-
Pensato, Umberto, Demchuk, Andrew M., Dreier, Jens P., Brennan, Kevin C., Sacco, Simona, and Romoli, Michele
- Abstract
Background: The term "aura" refers to a well-defined pattern of usually positive, progressive, and reversible neurological symptoms, with spreading depolarization as the underlying mechanism. While commonly associated with migraine, aura can also occur in other neurological disorders (i.e., cerebrovascular disorders). However, current terminology inadequately describes its different underlying clinical etiologies. Main body: We propose the following terminology and etiology-based clinical classification for the aura phenomenon: (i) Migrainous Aura (when the etiology is migraine), (ii) Non-migrainous Aura (when there is an alternative etiology), (iii) Aura of uncertain clinical etiology (when etiology is unclear), and (iv) Migrainous Infarction (a typical migrainous aura in a patient with migraine with aura associated with an infarction in a corresponding anatomical brain region). Conclusion: This nuanced classification aims to aid in the diagnostic evaluation and phenotyping of aura phenomenon, ultimately improving the diagnosis and management of the different associated neurological conditions. Moreover, it could promote effective communication and translational mechanistic research. [ABSTRACT FROM AUTHOR]
- Published
- 2025
- Full Text
- View/download PDF
3. Serial systemic immune inflammation indices: markers of acute migraine events or indicators of persistent inflammatory status?
- Author
-
Wijeratne, Tissa, Murphy, Melanie J., Wijeratne, Chanith, Martelletti, Paolo, Karimi, Leila, Apostolopoulos, Vasso, Sales, Carmela, Riddell, Nina, and Crewther, Sheila G.
- Abstract
Background: Migraine is the most common complex neurological disorder, affecting over a billion people worldwide. Neurogenic inflammation has long been recognized as a key factor in the pathophysiology of migraine though little research has been directed to investigating whether inflammation is greatest in migraine with aura or without, and whether inflammation is a permanent state in migraine or whether is an event related transitory state. Thus, the primary aim of this single-centre, retrospective study was to explore the potential clinical utility of the Serial Systemic Immune-Inflammatory Indices (SSIIi) as a comparative measure of duration and severity of inflammation derived from routine blood cell counts in migraine patients with aura and no-aura both within an acute inpatient setting and as outpatients. Specifically, we assessed the role of two serial white blood cell counts to calculate the SSIIi using the formula: neutrophil count x platelet count/lymphocyte count) between aura and no-aura migraine patients at time of admission to a tertiary care centre in Melbourne, Australia, and following 24 h post admission versus comparable serial measures in 20 out patients with migraine and ongoing symptoms. Main body: A retrospective analysis was conducted of medical records using baseline demographics and brain imaging findings from 186 migraine hospitalized in-patients who had at least two sets of white blood cell counts drawn within 24 h following their admission to the emergency department of Western Health a tertiary care center in Melbourne, Australia, over an 18-month period. Patients were categorized as having migraine with aura (MA) (N = 67) or without aura (MO) (N = 119) according to ICHD-3 criteria and compared to 2 serial measures in stable in-community acute migraineur controls (N = 20). A mixed-design ANOVA showed a significant main effect of SSIIi between patients with migraine with aura (MA) and migraine without aura (MO) during acute inpatient presentation, in comparison to a convenience sample of outpatients with migraine (MA and MO). Conclusion: SSIIi levels were significantly lower in patients with migraine with aura (MA), compared to MO. MA showed a greater, though non-significant, decrease between the two measurements compared to those with migraine without aura (MO) and outpatient controls, whose SSIIi levels remained consistently higher. The control group displayed similar findings to MO inpatients, suggesting persistent systemic inflammation in a subset of migraine patients regardless of in patient or outpatient of presentation and highlighting the need for future studies to more rigorously evaluate the role of systemic inflammation in migraine pathophysiology, chronicity, and progression though the multiple phases of migraine including the interictal phase. [ABSTRACT FROM AUTHOR]
- Published
- 2025
- Full Text
- View/download PDF
4. Anti-Calcitonin Gene-Related Peptide Monoclonal Antibody Is Effective for Preventing Migraine Aura Without Headache.
- Author
-
Shibata, Yasushi
- Subjects
- *
MIGRAINE aura , *SPREADING cortical depression , *CALCITONIN gene-related peptide , *ORAL drug administration , *MIGRAINE - Abstract
Background: Anti-calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are clinically effective in preventing the migraine attacks, photophobia, and migraine auras associated with headaches. However, no study has yet investigated the effectiveness of CGRP mAbs in preventing migraine aura without headache. Case report: A female patient of 49 years old presented with a long history (since age 10) of photosensitivity and typical migraine auras without a headache. The symptoms slightly responded to oral medication, lomerizine chloride, but did not completely resolve. Just one day after the administration of galcanezumab, her photo-hypersensitivity and migraine aura had completely resolved. Consequently, the administration of the oral migraine preventive medication was discontinued. Monthly galcanezumab at a dose of 120 mg was continuously given and she did not re-experience any auras or headaches. Conclusions: The use of CGRP mAbs can be considered as a potential treatment in preventing migraine aura without headache. Currently, CGRP mAb is indicated only for migraines with and without auras. Given our findings and the promising effects of this medication for this migraine subtype, a large clinical trial is required to better assess the effects and potential adverse events of CGRP mAb in patients with migraine aura without headache. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
5. Exploring the multifaceted characteristics of aura in migraine: A multicenter, cross-sectional study.
- Author
-
Dalla Volta, Giorgio, Russo, Antonio, Silvestro, Marcello, Ornello, Raffaele, Caponnetto, Valeria, Sacco, Simona, Zavarise, Paola, Cortinovis, Matteo, Lo Castro, Flavia, Guerzoni, Simona, Prudenzano, Maria Pia, Gentile, Martino, De Icco, Roberto, Vaghi, Gloria, Tassorelli, Cristina, De Tommaso, Marina, Scannicchio, Stefania, Rainero, Innocenzo, Granato, Antonio, and Sepe, Federica Nicoletta
- Subjects
- *
SPREADING cortical depression , *MIGRAINE aura , *SYMPTOMS , *MIGRAINE , *ANTI-inflammatory agents - Abstract
Background: Migraine with aura (MwA) is a debilitating disorder characterized by paroxysmal attacks of pain preceded or accompanied by reversible neurological symptoms. While the pathophysiology remains unclear, trigeminovascular system activation and cortical spreading depression have been implicated. This study aims to comprehensively investigate and characterize the diverse clinical features and manifestations of aura, as well as the types of acute medications self-administered for aura management. Methods: A multicenter, cross-sectional study was conducted using data from the Italian Headache Registry (RICe). Aura characteristics, frequency, duration and associated migraine premonitory symptoms were collected. Acute medication use and timing (headache or aura phase) were assessed. Results: The study included 272 patients with a diagnosis of MwA. Most patients (99.3%) experienced typical aura symptoms, with visual aura (96.3%) being the most prevalent, followed by sensory (33.0%) and speech and/or language aura (25.6%). Brainstem aura (8.5%) and motor aura (1.8%) were less common. Notably, 13.0% of patients reported aura relapses within 24 hours. Triptans (39.7%), non-steroidal anti-inflammatory drugs (47.8%) and nutraceuticals (59.9%) were commonly used for acute aura management. Conclusions: This study reports several different aura manifestations, highlighting atypical features, aura relapse rates and treatment approaches for aura. These findings could contribute to a deeper understanding of aura and its management in clinical settings. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
6. Chronic Hyperhomocysteinemia Impairs CSD Propagation and Induces Cortical Damage in a Rat Model of Migraine with Aura.
- Author
-
Gerasimova, Elena, Enikeev, Daniel, Yakovlev, Aleksey, Zakharov, Andrey, and Sitdikova, Guzel
- Subjects
- *
MIGRAINE aura , *LABORATORY rats , *SOMATOSENSORY cortex , *MIGRAINE , *LACTATE dehydrogenase , *SPREADING cortical depression - Abstract
Hyperhomocysteinemia (hHCY) is a metabolic disorder characterized by elevated levels of homocysteine in plasma. hHCY correlates with a high risk of migraine headaches, especially migraine with aura. Cortical spreading depression (CSD) is a wave of depolarization passing through neurons and glial cells of the cortex and is considered an electrophysiological correlate of migraine aura. The aim of the present study was to analyze neuronal activity and CSD in the somatosensory cortex of rats in vivo with prenatal hHCY and to assess cortex viability after 2 h of CSD generation. Female rats were fed a diet high in methionine, and their offspring with high homocysteine levels in plasma were further used in experiments. Recurrent CSD was evoked by local KCl application on the dura surface. Neuronal viability was assessed by measuring the activity of lactate dehydrogenase (LDH) in the brain and 2,3,5-triphenyltetrazolium chloride staining of the somatosensory cortex after two hours of CSD generation. Animals with hHCY exhibited higher neuronal activity, and more CSDs were generated in response to KCl, indicating higher cortical excitability. Propagation of recurrent CSD was impaired in supragranular cortical layers, and the recovery of multiple unit activity and evoked sensory potentials after CSD was delayed in the hHCY group. Finally, in animals with prenatal hHCY, an ischemic focus was identified as a consequence of multiple CSDs, along with elevated levels of LDH activity in brain tissues, suggestive of diminished neuronal viability. These findings imply that prolonged elevated levels of homocysteine may not only predispose to migraine with aura but also potentially elevate the risk of migrainous infarction. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
7. Elevation in body temperature may increase susceptibility to cortical spreading depression in a rat model
- Author
-
Eiji Kitamura, Naomi Kanazawa, Takahiro Iizuka, and Kazutoshi Nishiyama
- Subjects
Migraine ,Climate change ,Temperature ,Cortical spreading depression ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
One characteristic of migraine is recurrent headache attacks, which are known to be induced by changes in climatic variables such as atmospheric pressure, humidity, and outside temperature. However, the relationship between temperature changes and migraine remains unclear. Therefore, we investigated the relationship between body temperature changes and cortical spreading depression (CSD) using KCl-induced rat models of CSD. We initially induced CSD under controlled conditions at a room temperature of 28°C on an operating table maintained at 37°C. Subsequently, we controlled the operating table temperature to induce a second round of CSD under conditions of either a 10 ± 1% increase or decrease in body temperature. We ensured 1 h rest period between the first and second inductions of CSD. The results indicated that the number of CSDs significantly increased after body temperature elevation (before, 8.8 ± 1.2 times vs. after, 13.4 ± 1.3 times; p = 0.0003). The mean percentage change in cerebral blood flow decreased after body temperature increased (before, 33.1 ± 2.4% vs. after, 18.2 ± 1.4%; p = 0.006). There were no significant changes in CSD after body temperature decreased. The susceptibility of the cortex to CSD may increase under conditions of elevated body temperature.
- Published
- 2024
- Full Text
- View/download PDF
8. Arachidonic acid metabolites and cortical depression: From local to spatial model
- Author
-
Verisokin, Andrey Yu., Verveyko, Darya V., and Brazhe, Alexey R.
- Subjects
neurogliovascular unit ,cortical spreading depression ,astrocytes ,arachidonic acid ,arachidonic acid metabolites ,synaptic activity ,Physics ,QC1-999 - Abstract
Background and Objectives: According to known experimental data, various metabolites of arachidonic acid have a vasoconstrictor or vasodilator effect, which in turn affects neuronal activity. The level of metabolite production can be influenced in several ways: by regulating oxygen levels or by glutamate-dependent increases in astrocytic calcium concentrations in response to neuronal activity. To analyze possible patterns of activity of nervous tissue in response to changes in the metabolic profile, a mathematical model was developed, within the framework of which computational experiments were carried out both in the local case and on spatial patterns. Materials and Methods: The work proposes a point model and its further extension for a spatially distributed system of connected neurogliovascular units. To test the performance of the model, we include an external influence leading to an increase in neuronal potassium and the occurrence of cortical depression, and an external influence on calcium activity, in order to analyze the influence of arachidonic acid metabolites on the process under study. Results: A new point model of the neurogliovascular unit has been developed that simulates the effect of arachidonic acid metabolites on cortical spreading depression, while expanding the point model to a spatially distributed case allowed us to determine the ways in which astrocytic activity influences the spatiotemporal characteristics of the wave of cortically spreading depression. Numerical studies of point and spatial models have confirmed the correspondence of the solutions to the observed experimental effects, including those associated with the peculiarities of the influence of arachidonic acid metabolites on the speed, area and lifetime of depression waves. It is assumed that in the future the results of the theoretical study can be used to find ways to return nervous tissue to the normal state from pathological conditions that occur with epilepsy, migraines and other neurodegenerative conditions associated with the occurrence of cortical depression waves.
- Published
- 2024
- Full Text
- View/download PDF
9. Metabolic Pathophysiology of Cortical Spreading Depression: A Review.
- Author
-
Hill, Arren, Amendolara, Alfred B., Small, Christina, Guzman, Steve Cochancela, Pfister, Devin, McFarland, Kaitlyn, Settelmayer, Marina, Baker, Scott, Donnelly, Sean, Payne, Andrew, Sant, David, Kriak, John, and Bills, Kyle B.
- Subjects
- *
SPREADING cortical depression , *BRAIN injuries , *GLUCOSE metabolism , *ION transport (Biology) , *GENETIC markers - Abstract
Cortical spreading depression (CSD) is an electrophysiologic pathological state in which a wave of depolarization in the cerebral cortex is followed by the suppression of spontaneous neuronal activity. This transient spread of neuronal depolarization on the surface of the cortex is the hallmark of CSD. Numerous investigations have demonstrated that transmembrane ion transport, astrocytic ion clearing and fatigue, glucose metabolism, the presence of certain genetic markers, point mutations, and the expression of the enzyme responsible for the production of various arachidonic acid derivatives that participate in the inflammatory response, namely, cyclooxygenase (COX), all influence CSD. Here, we explore the associations between CSD occurrence in the cortex and various factors, including how CSD is related to migraines, how the glucose state affects CSD, the effect of TBI and its relationship with CSD and glucose metabolism, how different markers can be measured to determine the severity of CSD, and possible connections to oligemia, orexin, and leptin. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
10. Migraine and Stroke: A Scoping Review.
- Author
-
Nathan, Neal, Ngo, Angeline, and Khoromi, Suzan
- Subjects
- *
SPREADING cortical depression , *HEMORRHAGIC stroke , *DISEASE risk factors , *CEREBRAL circulation , *ISCHEMIC stroke , *MIGRAINE aura - Abstract
An increased risk of ischemic stroke in migraine with aura (MA) has been consistently demonstrated. The pathophysiology of risk factors is not yet well understood. Several mechanisms have been proposed to explain the association between MA and ischemic stroke including decreased focal cerebral blood flow and other phenomena linked with cortical spreading depression (CSD) as well as neurovascular pathology, which appear to play a key role in MA. In addition to genetic predisposition, other classic stroke risk factors such as atrial fibrillation, emboli, migraine-associated vasculopathy, endothelial dysfunction, platelet dysfunction, coagulation pathway abnormalities, and inflammatory factors have been examined and investigated. For further clarification, distinctions have been made between features of migrainous infarctions and non-migrainous infarctions among migraineurs. Furthermore, the association is less clear when considering the mixed results studying the risk of ischemic stroke in migraines without aura (MO) and the risk of hemorrhagic stroke in people with all types of migraine. Translational research is investigating the role of biomarkers which can help identify vascular links between stroke and migraine and lead to further treatment developments. We performed a scoping review of the PubMed database to further characterize and update the clinical connections between migraine and stroke. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
11. Effects of early monocular enucleation on cortical spreading depression in well-nourished and malnourished adult rats.
- Author
-
Guedes, Rubem Carlos Araujo, Monteiro, Jailma Santos, de Biase, Silvio, de Melo, Ana Paula Rocha, Borba, Juliana Maria Carrazzone, Diniz, Cristovam Wanderley Picanço, de Carvalho Noya, Arthur Gabriel Alves Furtado, and Prieto, Sonia Carolina Guerrero
- Subjects
- *
SPREADING cortical depression , *VISUAL pathways , *PARIETAL lobe , *SENSORY deprivation , *NUTRITIONAL status - Abstract
Sensory development is a complex process that can influence physiological and pathological factors. In laterally-eyed mammals, monocular enucleation (ME) during development and the subsequent lack of external sensory stimuli can result in permanent morphological and physiological changes. Malnutrition, especially in early life, also can cause permanent morphofunctional changes due to inadequate nutrient intake in both hemispheres. This study investigated the effects of early (postnatal day 7) ME and malnutrition during the suckling period on cortical excitability in adulthood (110–140 days of life). For this, we compared the speed propagation of cortical spreading depression in the occipital and parietal cortex of malnourished and well-nourished adult rats, previously suckled small-sized litters with three pups (L3/dam) medium-sized litters with six pups (L6/dam), and large-sized litters with twelve pups (L12/dam). The CSD velocity was augmented by the ME in the contralateral side of the removed eye in the parietal and occipital cortex. These findings suggest that visual sensory input deprivation is associated with permanent functional changes in the visual pathways, which can alter cortical excitability and lead to modifications in CSD propagation. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
12. Migraine Causality in Alpha-1 Antitrypsin Deficiency.
- Author
-
DEMİR ÜNAL, Esra
- Subjects
- *
MIGRAINE diagnosis , *VISION disorders , *NEUROINFLAMMATION , *ALPHA 1-antitrypsin deficiency , *MIGRAINE , *NAUSEA , *DISEASE risk factors , *DISEASE complications , *SYMPTOMS - Abstract
Alpha1-antitrypsin (A1AT) is an anti-inflammatory mediator with antiprotease activity associated with anti-inflammatory and immunomodulatory effects in various inflammatory conditions. A1AT deficiency (A1ATD) has been associated with various hyperinflammatory diseases, such as lung disease (emphysema and bronchiectasis), liver disease (chronic hepatitis, cirrhosis, and hepatoma), and skin diseases (panniculitis). Migraine with aura is one of the common migraine subtypes associated with neuroimmunologic activation and neuroinflammation which is associated with cortical spreading depression and glial hyperinflammation in etioradiopathogenesis, and the main mechanisms explained so far are hyperinflammation of pro-inflammatory mediators, sensitivity of trigeminal nerve fibers and pain-conjugated glial cells activation. In this case report, a causative perspective of migraine with aura and A1ATD was presented through etioradiopathogenetics mechanisms that show the central reflections of systemic hyperinflammatory processes, and the importance of peripheral hyperinflammatory conditions in migraine etiology was examined. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
13. Migraine and epilepsy frontiers, new challenges in its understanding: A case report
- Author
-
Jorge Sinche-Flores
- Subjects
Migraine without aura ,Epileptic seizures ,Migralepsy ,Cortical spreading depression ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
The relationship between migraine and epilepsy has been recognized since the 20th century. Currently, both pathologies share several characteristics, from molecular and electrophysiological mechanisms to their similarity in clinical symptoms and response to treatment. This is a case report of an 11-year-old male patient who presented with focal epilepsy at the age of 8 years. One year later, he developed episodes of migraine without aura followed by seizures with a frequency of 1–2 times per month, with headache duration ranging from 10 min to 6 h. At age 11, he also presented other episodes in which the headache occurred after the epileptic event and other episodes in which the headache was present both before and after the epileptic seizure. An interictal EEG study and an EEG study during a migraine attack showed the presence of high-voltage theta activity and bilateral temporo-parieto-occipital spikes with a greater expression in the right cerebral hemisphere. To our knowledge, this is the first report of an atypical presentation of migraine without aura and epileptic seizure. This case opens new challenges in the search for understanding between both pathologies.
- Published
- 2024
- Full Text
- View/download PDF
14. Post-traumatic Transient Neurological Dysfunction: A Proposal for Pathophysiology.
- Author
-
Lee, Seo-Young, Lee, Seung Jin, Kim, Sam Soo, Jun, Hyo Sub, Oh, Chungkun, Lin, Chen, and Phi, Ji Hoon
- Subjects
- *
MIGRAINE aura , *BRAIN injuries , *TRANSIENT ischemic attack , *CEREBRAL circulation , *PATHOLOGICAL physiology , *CLINICAL deterioration - Abstract
Unexplained neurological deterioration is occasionally observed in patients with traumatic brain injuries (TBIs). We aimed to describe the clinical features of post-traumatic transient neurological dysfunction and provide new insight into its pathophysiology. We retrospectively collected data from patients with focal neurological deterioration of unknown origin during hospitalization for acute TBI for 48 consecutive months. Brain imaging, including computed tomography, diffusion-weighted imaging and perfusion-weighted imaging, and electroencephalography were conducted during the episodes. Fourteen (2.0%) patients experienced unexplained focal neurological deterioration among 713 patients who were admitted for traumatic intracranial hemorrhage during the study period. Aphasia was the predominant symptom in all patients, and hemiparesis or hemianopia was accompanied in three patients. These symptoms developed within 14 days after trauma. Structural imaging did not show any significant interval change, and electroencephalography showed persistent arrhythmic slowing in the corresponding hemisphere in most patients. Perfusion imaging revealed increased cerebral blood flow in the symptomatic hemisphere. Surgical intervention and anti-seizure medications were ineffective in abolishing the symptoms. The symptoms disappeared spontaneously after 4 h to 1 month. Transient neurological dysfunction (TND) can occur during the acute phase of TBI. Although TND may last longer than a typical transient ischemic attack or seizure, it eventually resolves regardless of treatment. Based on our observation, we postulate that this is a manifestation of spreading depolarization occurring in the injured brain, which is analogous to migraine aura. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
15. Identification of Polymorphisms in EAAT1 Glutamate Transporter Gene SLC1A3 Associated with Reduced Migraine Risk.
- Author
-
Albury, Cassie L., Sutherland, Heidi G., Lam, Alexis W. Y., Tran, Ngan K., Lea, Rod A., Haupt, Larisa M., and Griffiths, Lyn R.
- Subjects
- *
GLUTAMATE transporters , *GENETIC polymorphisms , *MIGRAINE , *EXCITATORY amino acids , *SPREADING cortical depression , *SINGLE nucleotide polymorphisms , *SUMATRIPTAN - Abstract
Dysfunction in ion channels or processes involved in maintaining ionic homeostasis is thought to lower the threshold for cortical spreading depression (CSD), and plays a role in susceptibility to associated neurological disorders, including pathogenesis of a migraine. Rare pathogenic variants in specific ion channels have been implicated in monogenic migraine subtypes. In this study, we further examined the channelopathic nature of a migraine through the analysis of common genetic variants in three selected ion channel or transporter genes: SLC4A4, SLC1A3, and CHRNA4. Using the Agena MassARRAY platform, 28 single-nucleotide polymorphisms (SNPs) across the three candidate genes were genotyped in a case–control cohort comprised of 182 migraine cases and 179 matched controls. Initial results identified significant associations between migraine and rs3776578 (p = 0.04) and rs16903247 (p = 0.05) genotypes within the SLC1A3 gene, which encodes the EAAT1 glutamate transporter. These SNPs were subsequently genotyped in an independent cohort of 258 migraine cases and 290 controls using a high-resolution melt assay, and association testing supported the replication of initial findings—rs3776578 (p = 0.0041) and rs16903247 (p = 0.0127). The polymorphisms are in linkage disequilibrium and localise within a putative intronic enhancer region of SLC1A3. The minor alleles of both SNPs show a protective effect on migraine risk, which may be conferred via influencing the expression of SLC1A3. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
16. Brain Activation and Multiparametric Responses in Gerbils
- Author
-
Mayevsky, Avraham and Mayevsky, Avraham
- Published
- 2024
- Full Text
- View/download PDF
17. Systemic Vasospasm
- Author
-
Hummers, Laura K., Wigley, Fredrick M., editor, Herrick, Ariane L., editor, and Flavahan, Nicholas A., editor
- Published
- 2024
- Full Text
- View/download PDF
18. The glymphatic system in migraine and other headaches
- Author
-
Vittorini, Maria Grazia, Sahin, Aysenur, Trojan, Antonin, Yusifli, Sevil, Alashvili, Tamta, Bonifácio, Gonçalo V., Paposhvili, Ketevan, Tischler, Viktoria, Lampl, Christian, and Sacco, Simona
- Published
- 2024
- Full Text
- View/download PDF
19. Different vulnerability of fast and slow cortical oscillations to suppressive effect of spreading depolarization: state-dependent features potentially relevant to pathogenesis of migraine aura
- Author
-
Medvedeva, Tatiana M., Smirnova, Maria P., Pavlova, Irina V., and Vinogradova, Lyudmila V.
- Published
- 2024
- Full Text
- View/download PDF
20. Signatures of migraine aura in high-density-EEG.
- Author
-
Riederer, Franz, Beiersdorf, Johannes, Lang, Clemens, Pirker-Kees, Agnes, Klein, Antonia, Scutelnic, Adrian, Platho-Elwischger, Kirsten, Baumgartner, Christoph, Dreier, Jens P., and Schankin, Christoph
- Subjects
- *
MIGRAINE aura , *NEUROLOGICAL disorders , *SPECTRAL energy distribution , *SPREADING cortical depression , *MIGRAINE - Abstract
• Detection of CSD is of interest, since it is an emerging tool in neuromonitoring, guiding prognosis and therapeutic decisions. • During visual migraine auras, we found a contralateral decrease in alpha power spectral density as a probable signature of CSD. • Other features of CSD, probably occurring in the depth of the calcarine sulcus, were not detectable on the surface of the scalp. Cortical spreading depolarization is highly conserved among the species. It is easily detectable in direct cortical surface recordings and has been recorded in the cortex of humans with severe neurological disease. It is considered the pathophysiological correlate of human migraine aura, but direct electrophysiological evidence is still missing. As signatures of cortical spreading depolarization have been recognized in scalp EEG, we investigated typical spontaneous migraine aura, using full band high-density EEG (HD-EEG). In this prospective study, patients with migraine with aura were investigated during spontaneous migraine aura and interictally. Time compressed HD-EEG were analyzed for the presence of cortical spreading depolarization characterized by (a) slow potential changes below 0.05 Hz, (b) suppression of faster activity from 0.5 Hz − 45 Hz (c) spreading of these changes to neighboring regions during the aura phase. Further, topographical changes in alpha-power spectral density (8–14 Hz) during aura were analyzed. In total, 26 HD-EEGs were recorded in patients with migraine with aura, thereof 10 HD-EEGs during aura. Eight HD-EEGs were recorded in the same subject. During aura, no slow potentials were recorded, but alpha-power was significantly decreased in parieto-occipito-temporal location on the hemisphere contralateral to visual aura, lasting into the headache phase. Interictal alpha-power in patients with migraine with aura did not differ significantly from age- and sex-matched healthy controls. Unequivocal signatures of spreading depolarization were not recorded with EEG on the intact scalp in migraine. The decrease in alpha-power contralateral to predominant visual symptoms is consistent with focal depression of spontaneous brain activity as a consequence of cortical spreading depolarization but is not specific thereof. Cortical spreading depolarization is relevant in migraine, other paroxysmal neurological disorders and neurointensive care. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
21. Are anti-calcitonin gene-related peptide monoclonal antibodies effective in treating migraine aura? A pilot prospective observational cohort study.
- Author
-
Braca, Simone, Miele, Angelo, Stornaiuolo, Antonio, Cretella, Gennaro, De Simone, Roberto, and Russo, Cinzia Valeria
- Subjects
- *
MIGRAINE aura , *MONOCLONAL antibodies , *PEPTIDES , *SPREADING cortical depression , *ERENUMAB , *COHORT analysis - Abstract
Background: About 15% to one third of migraineurs experience aura symptoms. Aura is a reversible focal neurological phenomenon involving visual, sensory, speech, and motor symptoms that usually precede migraine pain. Monoclonal antibodies against calcitonin-related peptide (anti- CGRP mAbs) are effective in preventing chronic and episodic migraine, but little is known about their effectiveness on specifically preventing migraine with aura. Methods: This is a pilot prospective observational cohort study, aiming at evaluating the effectiveness and safety of Erenumab, Fremanezumab or Galcanezumab for the treatment of migraine aura. We enrolled 14 patients at the Headache Centre of University Federico II of Naples. Duration of follow-up was 12 months. We assessed mean monthly days with aura symptoms, with or without subsequent headache, as well as mean monthly days with headache and mean monthly MIDAS score, by reviewing standardized paper patient headache diaries every three months. Results: A significant decrease in mean monthly aura days was observed throughout the observation period (median baseline: 13, interquartile range: 4–16; after 12 months: 1, interquartile range: 0–3, p < 0.001). We observed a statistically significant decrease in mean monthly headache days as well (median baseline 21, interquartile range: 16–30; after 12 months: 5, interquartile range: 4–7, p < 0.001). During the 12-month treatment period, none of the 14 patients reported mild or serious adverse events. Conclusion: Our findings suggest that anti-CGRP mAbs are highly effective in migraine with aura, both in reducing mean monthly aura days and mean monthly days with headache. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
22. Advances in understanding migraine pathophysiology: a bench to bedside review of research insights and therapeutics.
- Author
-
Frimpong-Manson, Kofi, Ortiz, Yuma T., McMahon, Lance R., and Wilkerson, Jenny L.
- Subjects
LITERATURE reviews ,CALCITONIN gene-related peptide ,MIGRAINE ,PATHOLOGICAL physiology - Abstract
The individual and global burden of migraine is of such significance that there are accelerated efforts to develop new therapies. New migraine therapeutics are needed to address the current deficiencies that exist in the efficacy and adherence rate of approved anti-migraine medications. The recent discovery of the calcitonin gene related peptide as an add-on to the role of serotonin has markedly increased the range of new treatment options for acute and chronic migraine. Despite this, tackling the complexity of migraine disorders requires a complete understanding of its pathophysiology. Preclinical animal models can shed light on disease-related pathophysiology, including migraine. Indeed, the use of animal models has been instrumental in developing many therapeutics. However, an animal model is limited by the predictive and face validity of that model, and this extends to preclinical migraine models. In this review, a summary of the current understanding of the pathophysiology of migraine is given from both a preclinical and clinical perspective, and an emphasis is placed on the animal models of migraine. We will discuss the strengths and pitfalls of common preclinical migraine models as well as experimental research areas to explore further. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
23. Cellular Stress, Energy Constraints and the Energy Allocation Hypothesis of Sleep.
- Author
-
Schmidt, Markus H. and Schindler, Kaspar A.
- Subjects
SLEEP ,PHYSIOLOGICAL stress ,PROTEIN synthesis ,HOMEOSTASIS ,MENTAL depression - Abstract
A growing body of literature demonstrates a critical role for sleep in upregulating diverse biological processes related to protein synthesis, immune function, and cellular housekeeping such as intracellular transport and membrane repair. The energy allocation (EA) hypothesis places sleep in a broader context of resource optimization where sleep–wake partitioning of metabolic operations optimizes resource utilization. The EA hypothesis of sleep carries important implications in health, disease, and homeostatic mechanisms. Specifically, conditions that lead to cellular stress, energy constraints or depression of neuronal activity, such as epilepsy, ischemic stroke or cortical spreading depression, are here proposed to follow similar conserved processes that favor sleep. This review examines the role of local mechanisms, including cytokine release or the accumulation of adenosine, in downregulating wakefulness to favoring sleep, loss of functional connectivity and the upregulation sleep-coupled processes that promote survival. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
24. Vagus nerve stimulation inhibits cortical spreading depression via glutamate-dependent TrkB activation mechanism in the nucleus tractus solitarius.
- Author
-
Liu, Tzu-Ting, Chen, Shih-Pin, Wang, Shuu-Jiun, and Yen, Jiin-Cherng
- Subjects
- *
VAGUS nerve stimulation , *SPREADING cortical depression , *SOLITARY nucleus , *GLUTAMATE receptors , *MIGRAINE aura - Abstract
Background: Vagus nerve stimulation (VNS) was recently found to inhibit cortical spreading depression (CSD), the underlying mechanism of migraine aura, through activation of the nucleus tractus solitarius (NTS), locus coeruleus (LC) and dorsal raphe nucleus (DRN). The molecular mechanisms underlying the effect of VNS on CSD in these nuclei remain to be explored. We hypothesized that VNS may activate glutamate receptor-mediated tropomyosin kinase B (TrkB) signaling in the NTS, thereby facilitating the noradrenergic and serotonergic neurotransmission to inhibit CSD. Methods: To investigate the role of TrkB and glutamate receptors in non-invasive VNS efficacy on CSD, a validated KCl-evoked CSD rat model coupled with intra-NTS microinjection of selective antagonists, immunoblot and immunohistochemistry was employed. Results: VNS increased TrkB phosphorylation in the NTS. Inhibition of intra-NTS TrkB abrogated the suppressive effect of VNS on CSD and CSD-induced cortical neuroinflammation. TrkB was found colocalized with glutamate receptors in NTS neurons. Inhibition of glutamate receptors in the NTS abrogated VNS-induced TrkB activation. Moreover, the blockade of TrkB in the NTS attenuated VNS-induced activation of the LC and DRN. Conclusions: VNS induces the activation of glutamate receptor-mediated TrkB signaling in the NTS, which might modulate serotonergic and norepinephrinergic innervation to the cerebral cortex to inhibit CSD and cortical inflammation. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
25. Maternal voluntary physical exercise in the adult rat: evidence of exercise-associated differences in maternal food intake, and in brain effects on the progeny.
- Author
-
Vitor-de-Lima, Suenia Marcele, Figueira de Oliveira, Maria Luísa, Tavares, Izaura de Souza, Leandro, Carol Virgínia Góis, and Guedes, Rubem Carlos Araújo
- Subjects
- *
INGESTION , *WEIGHT gain , *FOOD consumption , *SPREADING cortical depression , *RECOGNITION (Psychology) , *LABORATORY rats , *FORM perception , *OXYGEN consumption - Abstract
Objectives: Maternal physical activity may impact behavioral and electrophysiological aspects of brain function, with short- and long-term effects on pre- and postnatal neurodevelopment of the offspring. This study evaluated in the rat the effects of maternal voluntary physical activity (MVPA) on food intake and weight gain in the dams, as well as anxiety-like behavior, short-term memory and the brain excitability-related phenomenon known as cortical spreading depression (CSD) on the mother-pup dyad. Methods: Female Wistar rats (n=33) were individually housed in cages containing a running wheel for a 30-days adaptation period before mating. Rats were classified as inactive (I); active (A) or very active (VA) according to the distance spontaneously travelled daily. During gestation, the dams continued to have access to the running wheel. Mothers and their respective pups (1 pup per mother) were evaluated in the open field test (OFT), object recognition test (ORT), elevated plus maze test (EPMT) and the CSD propagation features. Results: MVPA was directly associated with increased food intake and weight gain during gestation, and maternal anxiolytic-like behavioral responses in the OFT. Pups from VA mothers showed a high discrimination index for shape recognition memory (ORT) and decreased propagation velocities of CSD, when compared with the inactive group. Discussion: The data suggest that MVPA during the gestational period induces neuroplasticity and may modulate the brain functions in the mother-infant dyad in the rat. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
26. Effect of anti‐CGRP‐targeted therapy on migraine aura: Results of an observational case series study.
- Author
-
Cresta, Elena, Bellotti, Alessia, Rinaldi, Giovanni, Corbelli, Ilenia, and Sarchielli, Paola
- Subjects
- *
MIGRAINE aura , *SPREADING cortical depression , *MIGRAINE , *ERENUMAB , *MONOCLONAL antibodies , *CALCITONIN gene-related peptide - Abstract
Introduction: Limited clinical evidence is available regarding the potential effectiveness of anti‐CGRP monoclonal antibodies for the preventive treatment of migraine with aura. Aim of the Study: This observational study involved a series of migraine patients affected by either migraine with or without aura, who were investigated for any changes in their frequencies and their migraine aura attack characteristics observed during treatment with anti‐CGRP Mabs over a 1‐year period. Patients and Methods: Twelve migraine patients were included, seven of whom were treated with erenumab, 2 with fremanezumab, and 3 with galcanezumab. Clinical data were collected at baseline, which were defined as 3 months prior to the initiation of treatment, and thereafter at each trimester, over the 1‐year treatment period. The parameters included the number of headache and migraine days/month, the frequency of aura episodes, the number of days with acute drug intakes/month, and the scores from the migraine disability status scale (MIDAS), and the Headache Impact Test 6 (HIT‐6). Results: Anti‐CGRP Mbs antibodies induced significant decreases in mean headache and migraine without aura days per month, the number of days with medication intake, as well as MIDAS and HIT‐6 scores (p < 0.0001). In contrast, the anti‐CGRP Mab treatment did not appear to impact the frequency of migraine with aura attacks but seemed to reduce both the intensity and the duration of headache phases of migraine aura. Furthermore, some migraine patients referred to having aura attacks without headache over the course of the treatment period. Conclusions: Based on the above findings, we hypothesize that anti‐CGRP Mabs did not influence neuronal and vascular events related to cortical spreading depression (CSD) which is considered the pathophysiological substrate of aura. Conversely, these antibodies are able to counteract, via their peripheral mechanisms of action, the sensitization of the trigemino‐vascular pathway which is triggered by CSD. This aforementioned might explain why in our patients, migraine aura attacks remained unchanged in their frequencies, but the headache phases were either reduced or absent. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
27. Changes of migraine aura with advancing age of patients
- Author
-
Adrian Scutelnic, Hristina Drangova, Antonia Klein, Nedelina Slavova, Morin Beyeler, Julian Lippert, Norbert Silimon, Thomas R. Meinel, Marcel Arnold, Urs Fischer, Franz Riederer, Heinrich P. Mattle, Simon Jung, and Christoph J. Schankin
- Subjects
Cortical spreading depression ,Migraine with aura ,Differential diagnosis of migraine with aura and ischemic stroke in elderly ,Medicine - Abstract
Abstract Aim Given the similar presentation of migraine aura and acute ischemic stroke, advancing patient age might change the characteristics of migraine with aura (MA) and be clinically important. Clinical data, however, are limited. Experimental studies indicate a decrease in the magnitude of cortical spreading depression (CSD), the pathophysiological correlate of migraine aura, with advancing age. Our study aimed to assess the influence of age on the clinical features of MA. Methods Three hundred and forty-three patients were interviewed using a structured questionnaire. The questions covered the headache characteristics and symptom types including the characteristics of the C-criterion, as defined by the International Classification of Headache Disorders 3rd Edition. The association of age with MA characteristics was assessed. Results The median age was 29 (IQR 28–52) and 235 of the 343 patients were women (69%). Individual symptoms of the C-criterion such as gradual aura spreading over longer than 5 min (P
- Published
- 2023
- Full Text
- View/download PDF
28. Mechanisms of initiation of cortical spreading depression
- Author
-
Marina Vitale, Angelita Tottene, Maral Zarin Zadeh, KC Brennan, and Daniela Pietrobon
- Subjects
Migraine ,Cortical spreading depression ,Spreading depolarization ,Cerebral cortex ,Glutamate NMDA receptors ,Voltage-gated calcium channels ,Medicine - Abstract
Abstract Background There is increasing evidence from human and animal studies that cortical spreading depression (CSD) is the neurophysiological correlate of migraine aura and a trigger of migraine pain mechanisms. The mechanisms of initiation of CSD in the brain of migraineurs remain unknown, and the mechanisms of initiation of experimentally induced CSD in normally metabolizing brain tissue remain incompletely understood and controversial. Here, we investigated the mechanisms of CSD initiation by focal application of KCl in mouse cerebral cortex slices. Methods High KCl puffs of increasing duration up to the threshold duration eliciting a CSD were applied on layer 2/3 whilst the membrane potential of a pyramidal neuron located very close to the site of KCl application and the intrinsic optic signal were simultaneously recorded. This was done before and after the application of a specific blocker of either NMDA or AMPA glutamate receptors (NMDARs, AMPARs) or voltage-gated Ca2+ (CaV) channels. If the drug blocked CSD, stimuli up to 12–15 times the threshold were applied. Results Blocking either NMDARs with MK-801 or CaV channels with Ni2+ completely inhibited CSD initiation by both CSD threshold and largely suprathreshold KCl stimuli. Inhibiting AMPARs with NBQX was without effect on the CSD threshold and velocity. Analysis of the CSD subthreshold and threshold neuronal depolarizations in control conditions and in the presence of MK-801 or Ni2+ revealed that the mechanism underlying ignition of CSD by a threshold stimulus (and not by a just subthreshold stimulus) is the CaV-dependent activation of a threshold level of NMDARs (and/or of channels whose opening depends on the latter). The delay of several seconds with which this occurs underlies the delay of CSD initiation relative to the rapid neuronal depolarization produced by KCl. Conclusions Both NMDARs and CaV channels are necessary for CSD initiation, which is not determined by the extracellular K+ or neuronal depolarization levels per se, but requires the CaV-dependent activation of a threshold level of NMDARs. This occurs with a delay of several seconds relative to the rapid depolarization produced by the KCl stimulus. Our data give insights into potential mechanisms of CSD initiation in migraine.
- Published
- 2023
- Full Text
- View/download PDF
29. Advances in understanding migraine pathophysiology: a bench to bedside review of research insights and therapeutics
- Author
-
Kofi Frimpong-Manson, Yuma T. Ortiz, Lance R. McMahon, and Jenny L. Wilkerson
- Subjects
serotonin ,calcitonin gene related peptide (CGRP) ,cannabinoid ,rodent ,cortical spreading depression ,purinergic receptor ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
The individual and global burden of migraine is of such significance that there are accelerated efforts to develop new therapies. New migraine therapeutics are needed to address the current deficiencies that exist in the efficacy and adherence rate of approved anti-migraine medications. The recent discovery of the calcitonin gene related peptide as an add-on to the role of serotonin has markedly increased the range of new treatment options for acute and chronic migraine. Despite this, tackling the complexity of migraine disorders requires a complete understanding of its pathophysiology. Preclinical animal models can shed light on disease-related pathophysiology, including migraine. Indeed, the use of animal models has been instrumental in developing many therapeutics. However, an animal model is limited by the predictive and face validity of that model, and this extends to preclinical migraine models. In this review, a summary of the current understanding of the pathophysiology of migraine is given from both a preclinical and clinical perspective, and an emphasis is placed on the animal models of migraine. We will discuss the strengths and pitfalls of common preclinical migraine models as well as experimental research areas to explore further.
- Published
- 2024
- Full Text
- View/download PDF
30. Spreading Depolarizations Contribute to the Acute Behavior Deficits Associated With a Mild Traumatic Brain Injury in Mice.
- Author
-
Pinkowski, Natalie J., Fish, Betty, Mehos, Carissa J., Carlson, Victoria L., Hess, Brandi R., Mayer, Andrew R., and Morton, Russell A.
- Subjects
- *
BRAIN injuries , *PHYSIOLOGY , *BRAIN physiology , *SYMPTOMS , *SPREADING cortical depression - Abstract
Concussions or mild traumatic brain injuries (mTBIs) are often described and diagnosed by the acute signs and symptoms of neurological dysfunction including weakness, dizziness, disorientation, headaches, and altered mental state. The cellular and physiological mechanisms of neurological dysfunction and acute symptoms are unclear. Spreading depolarizations (SDs) occur after severe TBIs and have recently been identified in closed-skull mouse models of mTBIs. SDs are massive waves of complete depolarization that result in suppression of cortical activity for multiple minutes. Despite the clear disruption of brain physiology after SDs, the role of SDs in the acute neurological dysfunction and acute behavioral deficits following mTBIs remains unclear. We used a closed-skull mouse model of mTBI and a series of behavioral tasks collectively scored as the neurological severity score (NSS) to assess acute behavior. Our results indicate that mTBIs are associated with significant behavioral deficits in the open field and NSS tasks relative to sham-condition animals. The behavioral deficits associated with the mTBI recovered within 3 h. We show here that the presence of mTBI-induced bilateral SDs were significantly associated with the acute behavioral deficits. To identify the role of SDs in the acute behavioral deficits, we used exogenous potassium and optogenetic approaches to induce SDs in the absence of the mTBI. Bilateral SDs alone were associated with similar behavioral deficits in the open field and NSS tasks. Collectively, these studies demonstrate that bilateral SDs are linked to the acute behavioral deficits associated with mTBIs. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
31. Targeting CGRP pathways and aura: A peripheral site with a central effect.
- Author
-
Al-Karagholi, Mohammad Al-Mahdi
- Subjects
- *
MIGRAINE aura , *SPREADING cortical depression , *DRUG efficacy - Abstract
Targeting CGRP-pathways has substantially expanded our options for treating individuals with migraine. Although the efficacy of these drugs on migraine aura is yet to be fully revealed, it seems from existing studies that CGRP antagonism reduces the number of migraine auras. The present perspective summarizes the evidence linking CGRP to the migraine aura and proposes a model by which targeting the CGRP-pathways and, thus, inhibition the interaction between C- and Aδ-trigeminal fibers might reverse a possible high cortical glutamate level leading to a reduced number of migraine auras. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
32. Neurovascular dynamics of repeated cortical spreading depolarizations after acute brain injury
- Author
-
Zhao, Hanzhi T, Tuohy, Mary Claire, Chow, Daniel, Kozberg, Mariel G, Kim, Sharon H, Shaik, Mohammed A, and Hillman, Elizabeth MC
- Subjects
Biological Sciences ,Brain Disorders ,Stroke ,Neurosciences ,1.1 Normal biological development and functioning ,Underpinning research ,Neurological ,Acute Disease ,Animals ,Brain Injuries ,Calcium-Binding Proteins ,Cerebral Cortex ,Cortical Spreading Depression ,Female ,Hemodynamics ,Mice ,Mice ,Inbred C57BL ,Mice ,Transgenic ,Neurons ,Rose Bengal ,Thrombosis ,Thy-1 Antigens ,Vasoconstriction ,Voltage-Sensitive Dye Imaging ,cortical spreading depolarizations ,neurovascular dynamics ,photothrombosis ,wide-field optical mapping ,Biochemistry and Cell Biology ,Medical Physiology ,Biological sciences - Abstract
Cortical spreading depolarizations (CSDs) are increasingly suspected to play an exacerbating role in a range of acute brain injuries, including stroke, possibly through their interactions with cortical blood flow. We use simultaneous wide-field imaging of neural activity and hemodynamics in Thy1-GCaMP6f mice to explore the neurovascular dynamics of CSDs during and following Rose Bengal-mediated photothrombosis. CSDs are observed in all mice as slow-moving waves of GCaMP fluorescence extending far beyond the photothrombotic area. Initial CSDs are accompanied by profound vasoconstriction and leave residual oligemia and ischemia in their wake. Later, CSDs evoke variable responses, from constriction to biphasic to vasodilation. However, CSD-evoked vasoconstriction is found to be more likely during rapid, high-amplitude CSDs in regions with stronger oligemia and ischemia, which, in turn, worsens after each repeated CSD. This feedback loop may explain the variable but potentially devastating effects of CSDs in the context of acute brain injury.
- Published
- 2021
33. Ketamine for Critically Ill Patients with Severe Acute Brain Injury: A Systematic Review with Meta-analysis and Trial Sequential Analysis of Randomized Clinical Trials
- Author
-
Andreasen, Trine Hjorslev, Madsen, Frederik Andreas, Barbateskovic, Marija, Lindschou, Jane, Gluud, Christian, and Møller, Kirsten
- Published
- 2024
- Full Text
- View/download PDF
34. Brain Multiparametric Responses to Hyperbaric Hyperoxia
- Author
-
Mayevsky, Avraham and Mayevsky, Avraham
- Published
- 2023
- Full Text
- View/download PDF
35. Responses to Oxygen Toxicity After Various Treatments
- Author
-
Mayevsky, Avraham and Mayevsky, Avraham
- Published
- 2023
- Full Text
- View/download PDF
36. Effects of Age on the Responses to Hyperbaric Hyperoxia
- Author
-
Mayevsky, Avraham and Mayevsky, Avraham
- Published
- 2023
- Full Text
- View/download PDF
37. Typical Brain Mitochondrial Responses to Hyperbaric Oxygenation
- Author
-
Mayevsky, Avraham and Mayevsky, Avraham
- Published
- 2023
- Full Text
- View/download PDF
38. Effect of the Pressure Level on the Oxygen Toxicity Process
- Author
-
Mayevsky, Avraham and Mayevsky, Avraham
- Published
- 2023
- Full Text
- View/download PDF
39. Hyperbaric Oxygenation Affecting Traumatic Brain Injury
- Author
-
Mayevsky, Avraham and Mayevsky, Avraham
- Published
- 2023
- Full Text
- View/download PDF
40. Estrogen modulation of cortical spreading depression
- Author
-
Chiho Kudo, Andrea M. Harriott, Michael A. Moskowitz, Christian Waeber, and Cenk Ayata
- Subjects
Gonadal hormones ,Migraine ,Aura ,Estrogen replacement ,Cortical spreading depression ,Medicine - Abstract
Abstract Background and aims Cortical spreading depression (CSD), a transient neuronal and glial depolarization that propagates slowly across the cerebral cortex, is the putative electrophysiological event underlying migraine aura and a headache trigger. Migraine is three times more prevalent in women than men, linked to circulating female hormones. High estrogen levels or estrogen withdrawal may be a migraine trigger for many women. We, therefore, aimed to examine whether sex, gonadectomy, and female hormone supplementation and withdrawal affect the susceptibility to CSD. Methods To determine CSD susceptibility, we recorded the frequency of CSDs triggered during 2-h topical KCl application in intact or gonadectomized female and male rats, without or with estradiol or progesterone supplementation via daily intraperitoneal injections. Estrogen or progesterone treatment followed by withdrawal was studied in a separate cohort. To take the first step towards identifying potential mechanisms, we studied glutamate and GABAA receptor binding using autoradiography. Results The CSD frequency in intact female rats was higher than intact male and ovariectomized rats. We did not detect a change in CSD frequency during different stages of the estrous cycle in intact females. Daily estrogen injections for three weeks did not change CSD frequency. However, one-week estrogen withdrawal after two weeks of treatment significantly increased CSD frequency compared with the vehicle group in gonadectomized females. The same protocol of estrogen treatment and withdrawal was ineffective in gonadectomized males. In contrast to estrogen, daily progesterone injections for three weeks elevated CSD susceptibility, and one-week withdrawal after two weeks of treatment partially normalized this effect. Autoradiography did not reveal significant changes in glutamate or GABAA receptor binding density after estrogen treatment and withdrawal. Conclusions These data suggest that females are more susceptible to CSD, and sexual dimorphism is abrogated by gonadectomy. Moreover, estrogen withdrawal after prolonged daily treatment enhances CSD susceptibility. These findings may have implications for estrogen-withdrawal migraine, although the latter tends to be without aura.
- Published
- 2023
- Full Text
- View/download PDF
41. Advances on the correlation between epilepsy and cortical spreading depression
- Author
-
ZHANG Xu and WANG Xiang⁃qing
- Subjects
epilepsy ,cortical spreading depression ,review ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Cortical spreading depression (CSD) is a pathological depolarization wave caused by the collective depolarization of neurons that propagates slowly along the cerebral cortex and can transiently inhibit brain electrical activity, which is related to a variety of paroxysmal encephalopathy. CSD and epileptiform discharge are co ⁃ occurring electrophysiological phenomena. Factors causing CSD can also induce epileptic seizure. Inhibiting the occurrence and propagation of CSD may change the seizure threshold and reduce epileptic seizure, and the two are interrelated and interact on each other. This article reviews the research progress of the correlation between epilepsy and CSD, in order to improve the clinical understanding of the correlation between them.
- Published
- 2023
- Full Text
- View/download PDF
42. Mathematical Psychiatry: On Cortical Spreading Depression—A Review.
- Author
-
Nsugbe, Ejay
- Subjects
- *
SPREADING cortical depression , *MIGRAINE aura , *OPTICAL illusions , *NEUROLOGICAL disorders , *PSYCHIATRY - Abstract
The concept of migraine with aura (MwA) is a widespread condition that can affect up to 30% of migraine patients and manifests itself as a temporary visual illusion followed by a prolonged headache. It was initially pitched as a neurological disease, and observed that the spread of accompanying electrophysiological waves as part of the condition, which came to be known as cortical spreading depression (CSD). A strong theoretical basis for a link between MwA and CSD has eventually led to knowledge of the dynamics between the pair. In addition to experiment-based observations, mathematical models make an important contribution towards a numerical means of expressing codependent neural-scale manifestations. This provides alternate means of understanding and observing the phenomena while helping to visualize the links between the variables and their magnitude in contributing towards the emanation and dynamic pulsing of the condition. A number of biophysical mechanisms are believed to contribute to the MwA-CSD, spanning ion diffusion, ionic currents of membranes, osmosis, spatial buffering, neurotransmission, gap junctions, metabolic pumping, and synapse connections. As part of this review study, the various mathematical models for the description of the condition are expressed, reviewed, and contrasted, all of which vary in their depth, perspective, and level of information presented. Subsequent to this, the review looked into links between electrophysiological data-driven manifestations from measurements such as EEG and fMRI. While concluding remarks forged a structured pathway in the area on sub-themes that need to be investigated in order to strengthen and robustify the existing models, they include an accounting for inter-personal variability in models, sex and hormonal factors, and age groups, i.e., pediatrics vs. adults. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
43. Genetic Mechanisms of Migraine: Insights from Monogenic Migraine Mutations.
- Author
-
Gosalia, Helin, Karsan, Nazia, and Goadsby, Peter J.
- Subjects
- *
SPREADING cortical depression , *MIGRAINE aura , *SUMATRIPTAN , *MIGRAINE , *DISABILITIES , *GENOME-wide association studies , *NEUROLOGICAL disorders - Abstract
Migraine is a disabling neurological disorder burdening patients globally. Through the increasing development of preclinical and clinical experimental migraine models, advancing appreciation of the extended clinical phenotype, and functional neuroimaging studies, we can further our understanding of the neurobiological basis of this highly disabling condition. Despite increasing understanding of the molecular and chemical architecture of migraine mechanisms, many areas require further investigation. Research over the last three decades has suggested that migraine has a strong genetic basis, based on the positive family history in most patients, and this has steered exploration into possibly implicated genes. In recent times, human genome-wide association studies and rodent genetic migraine models have facilitated our understanding, but most migraine seems polygenic, with the monogenic migraine mutations being considerably rarer, so further large-scale studies are required to elucidate fully the genetic underpinnings of migraine and the translation of these to clinical practice. The monogenic migraine mutations cause severe aura phenotypes, amongst other symptoms, and offer valuable insights into the biology of aura and the relationship between migraine and other conditions, such as vascular disease and sleep disorders. This review will provide an outlook of what is known about some monogenic migraine mutations, including familial hemiplegic migraine, familial advanced sleep-phase syndrome, and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
44. Mechanisms of initiation of cortical spreading depression.
- Author
-
Vitale, Marina, Tottene, Angelita, Zarin Zadeh, Maral, Brennan, KC, and Pietrobon, Daniela
- Subjects
EVOKED potentials (Electrophysiology) ,BIOCHEMISTRY ,MIGRAINE ,PHENOMENOLOGICAL biology ,ANIMAL experimentation ,CELL receptors ,MENTAL depression ,CALCIUM ,MICE ,CEREBRAL cortex - Abstract
Background: There is increasing evidence from human and animal studies that cortical spreading depression (CSD) is the neurophysiological correlate of migraine aura and a trigger of migraine pain mechanisms. The mechanisms of initiation of CSD in the brain of migraineurs remain unknown, and the mechanisms of initiation of experimentally induced CSD in normally metabolizing brain tissue remain incompletely understood and controversial. Here, we investigated the mechanisms of CSD initiation by focal application of KCl in mouse cerebral cortex slices. Methods: High KCl puffs of increasing duration up to the threshold duration eliciting a CSD were applied on layer 2/3 whilst the membrane potential of a pyramidal neuron located very close to the site of KCl application and the intrinsic optic signal were simultaneously recorded. This was done before and after the application of a specific blocker of either NMDA or AMPA glutamate receptors (NMDARs, AMPARs) or voltage-gated Ca
2+ (CaV ) channels. If the drug blocked CSD, stimuli up to 12–15 times the threshold were applied. Results: Blocking either NMDARs with MK-801 or CaV channels with Ni2+ completely inhibited CSD initiation by both CSD threshold and largely suprathreshold KCl stimuli. Inhibiting AMPARs with NBQX was without effect on the CSD threshold and velocity. Analysis of the CSD subthreshold and threshold neuronal depolarizations in control conditions and in the presence of MK-801 or Ni2+ revealed that the mechanism underlying ignition of CSD by a threshold stimulus (and not by a just subthreshold stimulus) is the CaV -dependent activation of a threshold level of NMDARs (and/or of channels whose opening depends on the latter). The delay of several seconds with which this occurs underlies the delay of CSD initiation relative to the rapid neuronal depolarization produced by KCl. Conclusions: Both NMDARs and CaV channels are necessary for CSD initiation, which is not determined by the extracellular K+ or neuronal depolarization levels per se, but requires the CaV -dependent activation of a threshold level of NMDARs. This occurs with a delay of several seconds relative to the rapid depolarization produced by the KCl stimulus. Our data give insights into potential mechanisms of CSD initiation in migraine. [ABSTRACT FROM AUTHOR]- Published
- 2023
- Full Text
- View/download PDF
45. Changes of migraine aura with advancing age of patients.
- Author
-
Scutelnic, Adrian, Drangova, Hristina, Klein, Antonia, Slavova, Nedelina, Beyeler, Morin, Lippert, Julian, Silimon, Norbert, Meinel, Thomas R., Arnold, Marcel, Fischer, Urs, Riederer, Franz, Mattle, Heinrich P., Jung, Simon, and Schankin, Christoph J.
- Subjects
PREVENTION of mental depression ,DIAGNOSIS of epilepsy ,MIGRAINE diagnosis ,EXPERIMENTAL design ,DISEASE progression ,NOSOLOGY ,ISCHEMIC stroke ,AGE distribution ,INTERVIEWING ,AGING ,DESCRIPTIVE statistics ,RESEARCH funding ,HEADACHE ,OLD age - Abstract
Aim: Given the similar presentation of migraine aura and acute ischemic stroke, advancing patient age might change the characteristics of migraine with aura (MA) and be clinically important. Clinical data, however, are limited. Experimental studies indicate a decrease in the magnitude of cortical spreading depression (CSD), the pathophysiological correlate of migraine aura, with advancing age. Our study aimed to assess the influence of age on the clinical features of MA. Methods: Three hundred and forty-three patients were interviewed using a structured questionnaire. The questions covered the headache characteristics and symptom types including the characteristics of the C-criterion, as defined by the International Classification of Headache Disorders 3
rd Edition. The association of age with MA characteristics was assessed. Results: The median age was 29 (IQR 28–52) and 235 of the 343 patients were women (69%). Individual symptoms of the C-criterion such as gradual aura spreading over longer than 5 min (P < 0.001), two or more aura symptoms occurring in succession (P = 0.005), duration of at least one MA symptom for longer than 60 min (P = 0.004), and associated headache (P = 0.01) were more frequent in younger patients. The number of symptoms including the C-characteristics decreased with increasing age (P < 0.001). Patients with sensory (P < 0.001), motor (P = 0.004) and speech disturbance (P = 0.02) were younger, and older patients with headache had less photophobia (P = 0.04) and phonophobia (P = 0.03). Sensitivity analyses yielded similar results. Conclusion: The frequency of typical characteristics of migraine aura and migraine headache including photophobia and phonophobia decreases with advancing patient age. This might have potentially difficult implications for the diagnosis of MA in the elderly. [ABSTRACT FROM AUTHOR]- Published
- 2023
- Full Text
- View/download PDF
46. Which Spreading Depolarizations Are Deleterious To Brain Tissue?
- Author
-
Shuttleworth, C William, Andrew, R David, Akbari, Yama, Ayata, Cenk, Balu, Ramani, Brennan, KC, Boutelle, Martyn, Carlson, Andrew P, Dreier, Jens P, Fabricius, Martin, Farkas, Eszter, Foreman, Brandon, Helbok, Raimund, Henninger, Nils, Jewell, Sharon L, Jones, Stephen C, Kirov, Sergei A, Lindquist, Britta E, Maciel, Carolina B, Okonkwo, David, Reinhart, Katelyn M, Robertson, R Meldrum, Rosenthal, Eric S, Watanabe, Tomas, and Hartings, Jed A
- Subjects
Biomedical and Clinical Sciences ,Neurosciences ,Clinical Sciences ,Brain Disorders ,Animals ,Brain ,Brain Injuries ,Cortical Spreading Depression ,Electroencephalography ,Humans ,Migraine with Aura ,Spreading depression ,Spreading depolarization ,Ischemia ,Trauma ,Subarachnoid hemorrhage ,Neurology & Neurosurgery ,Clinical sciences ,Nursing - Abstract
Spreading depolarizations (SDs) are profound disruptions of cellular homeostasis that slowly propagate through gray matter and present an extraordinary metabolic challenge to brain tissue. Recent work has shown that SDs occur commonly in human patients in the neurointensive care setting and have established a compelling case for their importance in the pathophysiology of acute brain injury. The International Conference on Spreading Depolarizations (iCSD) held in Boca Raton, Florida, in September of 2018 included a discussion session focused on the question of "Which SDs are deleterious to brain tissue?" iCSD is attended by investigators studying various animal species including invertebrates, in vivo and in vitro preparations, diseases of acute brain injury and migraine, computational modeling, and clinical brain injury, among other topics. The discussion included general agreement on many key issues, but also revealed divergent views on some topics that are relevant to the design of clinical interventions targeting SDs. A draft summary of viewpoints offered was then written by a multidisciplinary writing group of iCSD members, based on a transcript of the session. Feedback of all discussants was then formally collated, reviewed and incorporated into the final document. It is hoped that this report will stimulate collection of data that are needed to develop a more nuanced understanding of SD in different pathophysiological states, as the field continues to move toward effective clinical interventions.
- Published
- 2020
47. Cortical pain induced by optogenetic cortical spreading depression: from whole brain activity mapping
- Author
-
Chenghui Pi, Wenjing Tang, Zhishuai Li, Yang Liu, Qi Jing, Wei Dai, Tao Wang, Chunxiao Yang, and Shengyuan Yu
- Subjects
Cortical spreading depression ,Whole-brain activity mapping ,Cortical pain ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Highlights 1. We established an optogenetic mouse CSD model without irritation dura, which could mimic the behaviors of headache and photophobia. 2. It was the first time to depict a broad, unbiased neuronal activity map throughout the mouse brain after CSD. 3. Results of whole brain image and immunofluorescence staining showed that optogenetic CSD could activate multiple sensory-related networks without activating thalamus or TNC to induce cortical pain.
- Published
- 2022
- Full Text
- View/download PDF
48. Meningeal Mechanisms and the Migraine Connection.
- Author
-
Levy, Dan and Moskowitz, Michael A.
- Subjects
- *
NEURAL stimulation , *DURA mater , *MIGRAINE , *MENINGES , *TRIGEMINAL nerve - Abstract
Migraine is a complex neurovascular pain disorder linked to the meninges, a border tissue innervated by neuropeptide-containing primary afferent fibers chiefly from the trigeminal nerve. Electrical or mechanical stimulation of this nerve surrounding large blood vessels evokes headache patterns as in migraine, and the brain, blood, and meninges are likely sources of headache triggers. Cerebrospinal fluid may play a significant role in migraine by transferring signals released from the brain to overlying pain-sensitive meningeal tissues, including dura mater. Interactions between trigeminal afferents, neuropeptides, and adjacent meningeal cells and tissues cause neurogenic inflammation, a critical target for current prophylactic and abortive migraine therapies. Here we review the importance of the cranial meninges to migraine headaches, explore the properties of trigeminal meningeal afferents, and briefly review emerging concepts, such as meningeal neuroimmune interactions, that may one day prove therapeutically relevant. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
49. Treatment of hemiplegic migraine with anti‐calcitonin gene‐related peptide monoclonal antibodies: A case series in a tertiary‐care headache center.
- Author
-
Danno, Daisuke, Ishizaki, Kumiko, Kikui, Shoji, and Takeshima, Takao
- Subjects
- *
THERAPEUTIC use of monoclonal antibodies , *MIGRAINE , *CALCITONIN , *TERTIARY care , *TREATMENT effectiveness , *CELLULAR signal transduction , *CASE studies , *PEPTIDES , *HEMIPLEGIA , *IMMUNOTHERAPY , *CHEMICAL inhibitors - Abstract
Hemiplegic migraine (HM) is a subtype of migraine with aura that includes motor weakness; such headaches can be excruciating. The presence of not only headache but also aura symptoms of HM increase the burden on patients, and the treatment of HM is sometimes challenging. Monoclonal antibodies (mAbs) targeting the calcitonin gene‐related peptide (CGRP) pathway are novel migraine preventive treatments that have shown promising efficacy in patients with migraine; however, there have been no reports regarding their efficacy in HM to date. Six patients with HM were treated with galcanezumab in a tertiary‐care headache center. After 3 months of treatment, the number of monthly days with headache of at least moderate severity was reduced in three patients. The number of days each month with weakness was also reduced in four patients. Furthermore, the Patient's Global Impression of Change and change in Migraine Disability Assessment total score, were improved in five of the six patients after the treatment; however, the change from baseline in days with bothersome symptoms did not show any specific trends in our patients. Notably, no adverse events were reported during the treatments. The mechanism underlying the improvement in aura symptoms in our patients is not clear; however, we speculate that a small amount of CGRP mAbs have a direct mode of action in the central nervous system; alternatively, blocking the CGRP pathway in the periphery may secondarily inhibit cortical spreading depression. While prudence must be practiced, galcanezumab was still generally effective in HM and well tolerated. Further prospective clinical studies will more clearly elucidate the effects of CGRP mAbs in patients with HM. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
50. Migrainous infarction: A serious complication of a common condition.
- Author
-
Johnson, Emily and Grosel, John
- Subjects
EVOKED potentials (Electrophysiology) ,BRAIN diseases ,MIGRAINE ,INFARCTION ,ISCHEMIC stroke ,MAGNETIC resonance imaging ,VASODILATION ,VASOCONSTRICTION ,VISION disorders ,HEMORRHAGE ,DISEASE complications - Abstract
Migrainous infarction is a rare neurologic condition that stems from an ordinary migraine with aura, and can cause ischemic stroke in young women. The pathophysiology of migrainous infarction is not entirely understood. An aura that is similar to previous auras but lasts longer than 60 minutes, along with evidence of acute ischemia on MRI, are diagnostic of migrainous infarction. Treatment aimed at minimizing migraine with aura is the most important preventive measure clinicians can take to help patients avoid this complication of migraine. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.