Harnessing migraines for neural regeneration

The success of naturalistic or therapeutic neuroregeneration likely depends on an internal milieu that facilitates the survival, proliferation, migration, and differentiation of stem cells and their assimilation into neural networks. Migraine attacks are an integrated sequence of physiological processes that may protect the brain from oxidative stress by releasing growth factors, suppressing apoptosis, stimulating neurogenesis, encouraging mitochondrial biogenesis, reducing the production of oxidants, and upregulating antioxidant defenses. Thus, the migraine attack may constitute a physiologic environment conducive to stem cells. In this paper, key components of migraine are reviewed - neurogenic inflammation with release of calcitonin gene-related peptide (CGRP) and substance P, plasma protein extravasation, platelet activation, release of serotonin by platelets and likely by the dorsal raphe nucleus, activation of endothelial nitric oxide synthase (eNOS), production of brain-derived neurotrophic factor (BDNF) and, in migraine aura, cortical spreading depression - along with their potential neurorestorative aspects. The possibility is considered of using these components to facilitate successful stem cell transplantation. Potential methods for doing so are discussed, including chemical stimulation of the TRPA1 ion channel, conjoint activation of a subset of migraine components, invasive and noninvasive deep brain stimulation of the dorsal raphe nucleus, transcranial focused ultrasound, and stimulation of the Zusanli (ST36) acupuncture point.