Calcitonin gene-related peptide (CGRP) influences cortical spreading depolarization (CSD) in adult rats - Could this be important in brain pathophysiology?
| Main Authors: | F. GIMENO-FERRER1, ;, R. BAUER2, A. LEHMENKUHLER3,, H.-G. SCHAIBLE1 |
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| Format: | Proceeding poster Journal |
| Bahasa: | eng |
| Terbitan: |
, 2022
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| Subjects: | |
| Online Access: |
https://zenodo.org/record/6323078 |
Daftar Isi:
- It is known from the literature that CGRP plays an important role in migraine, and antagonizing CGRP is an effective treatment against migraine pain. CSD, the correlate of the migraine aura, is able to release CGRP in rat neocortical slices. CGRP may increase neuronal excitability, but a possible interference with CSD has not been investigated yet. To test this, we applied CGRP at different concentrations topically to a restricted part of the cortical surface and compared the electrocorticogram and CSD there with the untreated brain area. In spontaneously breathing anesthetized adult rats (sodium thiopentone, 100 mg/kg, i.p.) CSDs were recorded in cerebral cortex with two pairs of glass micropipettes (distance 5-6 mm) at depths of 400 and 1200 μm in two areas of the cortex, separated by a wall. In the untreated area, CSD was elicited by a microinjection of 1 M KCl (100 kPa, 300 ms up to 1 s) into the grey matter at intervals of 30 min. In the remote area 100 μl of CGRP at concentrations from 10-8 M to 10-5 M were applied topically and left there for three hours. In the treated area additionally changes in extracellular potassium concentration and in both areas regional cortical blood flow were measured. In all rats tested, a pulse of KCl elicited a single propagating CSD. The topical application of CGRP to the brain surface reduced the amplitudes of CSD in the treated area (10-5 M to 60 % of controls; 10-8 M to 70 % of controls; untreated to 85-90 % of controls) and slowed the propagation velocity (10-5 M from 3.0 to 2.6 cm/s; 10-8 M from 2.4 to 2.2 cm/s). Rarely spontaneous CSDs were observed originating from the CGRP treated area. In another few rats CGRP induced focal ictal activity after 2-3 hours of application that did not spread into the untreated cortex. This activity was accompanied by increases in extracellular potassium concentration and occurred at intervals of 8-10 min. Our results identify the neuropeptide CGRP as a candidate that could interfere with CSD by changing neuronal excitability. In contrast to other previously investigated neuropeptides, the capability of CGRP to ignite CSD at the same concentrations varies markedly between the animals. This has to be taken into account when using CGRP as a model for neuroinflammation or disturbed brain homeostasis.