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For monitoring the long\u2010term safety of these drugs, it is helpful to consider the role of CGRP in brain functioning.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Qualitative review of the preclinical literature on CGRP in brain physiology and pathophysiology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Within the brain, CGRP is upregulated by stresses such as ischemia, injury, hyperthermia, and seizure, and activates neuroprotective processes. Thus, CGRP buffers intracellular calcium, triggers antiapoptotic signaling, upregulates a number of neurotrophins (including insulin\u2010like growth factor\u20101\/IGF\u20101, basic fibroblast growth factor\/bFGF, and nerve growth factor\/NGF), reduces brain edema, and likely increases antioxidant defenses. When released outside the blood\u2010brain barrier, CGRP likely protects the endothelium, upregulates growth factor signaling from the endothelium to the brain parenchyma, strengthens the blood\u2010brain barrier, protects the immune privilege of the brain by inhibiting the movement of neutrophils and monocytes, and facilitates neurogenesis and angiogenesis at stem cell niches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CGRP participates in a wide range of neuroprotective processes. In theory, migraineurs with comorbid brain pathology might be at increased risk from CGRP inhibition. However, the extent of compensating processes is unknown and will determine whether these risks materialize in practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.13591","type":"journal-article","created":{"date-parts":[[2019,7,22]],"date-time":"2019-07-22T02:13:55Z","timestamp":1563761635000},"page":"1339-1357","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["CGRP and Brain Functioning: Cautions for Migraine Treatment"],"prefix":"10.1111","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5943-3156","authenticated-orcid":false,"given":"Jonathan M.","family":"Borkum","sequence":"first","affiliation":[{"name":"Department of Psychology University of Maine Orono ME USA"},{"name":"Health Psych Maine Waterville ME 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