From spreading depolarization to epilepsy with neuroinflammation: The role of CGRP in cortex Article Swipe
Fátima Gimeno-Ferrer
,
Annett Eitner
,
Reinhard Bauer
,
A. Lehmenkühler
,
Marie-Luise Edenhofer
,
Michaela Kress
,
Hans‐Georg Schaible
,
Frank Richter
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1016/j.expneurol.2022.114152
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1016/j.expneurol.2022.114152
CGRP release plays a major role in migraine pain by activating the trigeminal pain pathways. Here we explored putative additional effects of CGRP on cortical circuits and investigated whether CGRP affects cortical excitability, cortical spreading depolarization (CSD), a phenomenon associated with migraine aura, blood-brain-barrier (BBB) and microglial morphology. We used immunohistochemistry to localize CGRP and the CGRP receptor (CGRP-R) in native cortex and evaluated morphology of microglia and integrity of the BBB after exposure to CGRP. In anesthetized rats we applied CGRP and the CGRP-R antagonist BIBN4096BS locally to the exposed cortex and monitored the spontaneous electrocorticogram and CSDs evoked by remote KCl pressure microinjection. In mouse brain slices CGRP effects on neuronal activity were explored by multielectrode array. CGRP immunoreactivity was detectable in intracortical vessels, and all cortical neurons showed CGRP-R immunoreactivity. In rat cortex in vivo, topical CGRP induced periods of epileptiform discharges, however, also dose-dependently reduced CSD amplitudes and propagation velocity. BIBN4096BS prevented these effects. CGRP evoked synchronized bursting activity in mouse cortical but not in cerebellar slices. Topical application of CGRP to rat cortex induced plasma extravasation and this was associated with reduced ramification of microglial cells. From these findings we conclude that CGRP induces a pathophysiological state in the cortex, consisting in neuronal hyperexcitability and neuroinflammation. Thus, CGRP may have a pronounced impact on brain functions during migraine episodes supporting the benefit of CGRP antagonists for clinical use. However, increased cortical CGRP may end the CSD-induced aura phase of migraine.
Related Topics
Concepts
Calcitonin gene-related peptide
Cortical spreading depression
Neuroscience
Cerebral cortex
Chemistry
Cortex (anatomy)
Medicine
Migraine
Neuropeptide
Internal medicine
Receptor
Psychology
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1016/j.expneurol.2022.114152
- OA Status
- hybrid
- Cited By
- 20
- References
- 60
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4283520943
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4283520943Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1016/j.expneurol.2022.114152Digital Object Identifier
- Title
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From spreading depolarization to epilepsy with neuroinflammation: The role of CGRP in cortexWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2022Year of publication
- Publication date
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2022-06-26Full publication date if available
- Authors
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Fátima Gimeno-Ferrer, Annett Eitner, Reinhard Bauer, A. Lehmenkühler, Marie-Luise Edenhofer, Michaela Kress, Hans‐Georg Schaible, Frank RichterList of authors in order
- Landing page
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https://doi.org/10.1016/j.expneurol.2022.114152Publisher landing page
- Open access
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YesWhether a free full text is available
- OA status
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hybridOpen access status per OpenAlex
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https://doi.org/10.1016/j.expneurol.2022.114152Direct OA link when available
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Calcitonin gene-related peptide, Cortical spreading depression, Neuroscience, Cerebral cortex, Chemistry, Cortex (anatomy), Medicine, Migraine, Neuropeptide, Internal medicine, Receptor, PsychologyTop concepts (fields/topics) attached by OpenAlex
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20Total citation count in OpenAlex
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2025: 6, 2024: 5, 2023: 5, 2022: 4Per-year citation counts (last 5 years)
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60Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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