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Updated: Jan 21, 2026

Investigating Migraine-Like Behavior Using Light Aversion in Mice
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CGRP and Brain Functioning: Cautions for Migraine Treatment.

Jonathan M Borkum1,2

  • 1Department of Psychology, University of Maine, Orono, ME, USA.

Headache
|July 23, 2019
PubMed
Summary

Calcitonin gene-related peptide (CGRP) plays a vital neuroprotective role in the brain. Understanding CGRP

Keywords:
calcitonin gene-related peptideischemic strokemigrainemultiple sclerosisoxidative stresstraumatic brain injury

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Migraine Research

Background:

  • Calcitonin gene-related peptide (CGRP) is a key therapeutic target for migraine treatment.
  • Approved monoclonal antibodies and gepants targeting CGRP are in clinical trials.
  • Long-term safety monitoring necessitates understanding CGRP's role in brain function.

Purpose of the Study:

  • To review preclinical literature on CGRP's function in brain physiology and pathophysiology.
  • To inform the safety assessment of CGRP-targeting migraine therapies.

Main Methods:

  • Qualitative review of preclinical studies.
  • Focus on CGRP's role in brain physiology and pathophysiology.

Main Results:

  • CGRP is upregulated by brain stresses like ischemia and seizure, activating neuroprotective mechanisms.
  • It buffers calcium, triggers antiapoptotic signals, upregulates neurotrophins (IGF-1, bFGF, NGF), reduces edema, and enhances antioxidant defenses.
  • Outside the blood-brain barrier, CGRP protects endothelium, strengthens barrier integrity, maintains immune privilege, and promotes neurogenesis and angiogenesis.

Conclusions:

  • CGRP is integral to numerous neuroprotective processes within the brain.
  • Migraine patients with existing brain conditions may face risks from CGRP inhibition.
  • The clinical significance of these risks depends on the extent of compensatory mechanisms, which remain to be fully elucidated.