Brain Health and Migraine



Richard Kraig MD, PhD, FANA focuses his research on deciphering how the brain can protect itself against neurological disease. The brain is unique among organ structures. It can alter its regional, cellular and molecular structure and function in response to activity to preserve and enhance brain health.  This capacity is evidenced by “environmental enrichment” or increased intellectual, physical and social activity in preclinical studies and by exercise and creative thought in humans. 

Environmental enrichment can reduce subsequent brain disease by half in a wide range of neurodegenerative disorders including but not limited to Alzheimer’s disease, Parkinson’s disease and multiple sclerosis,as well as reducing cognitive decline from aging. It also has the ability to be similarly effective in patients suffering from migraine and epilepsy. The Kraig lab currently focuses on two fundamental protective signaling systems involved in environmental enrichment: 1) the ability of insulin-like growth factor (IGF-1) to protect against migraine, epilepsy and chronic pain as seen in fibromyalgia; 2) the ability of exosomes derived from stimulated dendritic cells to lessen demyelination, promote remyelination and reduce inflammation associated with demyelinating disorders including multiple sclerosis, traumatic brain injury and as well as cognitive decline from aging.

Experimental evidence from the Kraig lab shows that IGF-1 reduces the impact of nociceptive activation of the trigeminal system in two preclinical models of migraine, recurrent spreading depression and systemic injection of nitroglycerin.  In both models a single dose of nasally delivered IGF-1 effectively reduced trigeminal ganglion oxidative stress and calcitonin gene-related peptide (CGRP) levels, two key mediators of migraine pain.  In addition, nasal delivery of IGF-1 inhibits trigeminocervical complex nociceptive neuronal activation after recurrent spreading depression or nitroglycerin treatment. Finally, nasal IGF-1 effectively inhibits spreading depression itself, the most likely cause of migraine aura and perhaps a cause of migraine pain.  Collectively these findings have led to a series of national and international patents that are the basis for commercialization of nasal IGF-1 as a novel environmental enrichment-based mimetic for migraine, epilepsy and chronic pain as well as continued basic research directed toward understanding the cellular and molecular bases for IGF-1’s protective effect on brain. 

In a second major direction, the Kraig team is exploring their finding that environmental enrichment produces serum-based exosomes that promote myelination and reduce neuroinflammation. Exosomes are nanovesicles released from cells that contain selected mRNAs, microRNAs and proteins. The team went on to find that dendritic cells from rats and humans could be stimulated in culture to produce exosomes analogous to those produced by environmental enrichment. This has also led to a series of national and international patents and a plan to develop these nutritive exosomes into a novel platform for treating neurodegenerative diseases that involve myelin loss. Work is also directed to understanding the cellular and molecular mechanism both within and outside of brain by which these nutritive exosomes improve brain health.