Linking Traumatic Brain Injury, Sleep Disruption and Post-Traumatic Headache: a Potential Role for Glymphatic Pathway Dysfunction
Purpose of the Review
Traumatic brain injury (TBI) is a major public health concern in the USA and worldwide. Sleep disruption and headaches are two of the most common problems reported by patients after TBI. In this manuscript, we review the current knowledge regarding the relation between post-traumatic sleep disruption and headaches. We also describe the role of the glymphatic system as a potential link between TBI, sleep, and headaches.
Recent studies show a reciprocal relation between post-traumatic sleep disruption and headaches: patients with sleep disruption after TBI report more headaches, and post-traumatic headaches are a risk factor for developing disrupted sleep. Despite this clinical association, the exact mechanisms linking post-traumatic sleep disruption and headaches are not well understood. The glymphatic pathway, a newly described brain–wide network of perivascular spaces that supports the clearance of interstitial solutes and wastes from the brain, is active primarily during sleep, and becomes dysfunctional after TBI. We propose a model where changes in glymphatic function caused by TBI and post-traumatic sleep disruption may impair the clearance of neuropeptides involved in the pathogenesis of post-traumatic headaches, such as CGRP.
The relation between TBI, post-traumatic sleep disruption, and post-traumatic headaches, although well documented in the literature, remains poorly understood. Dysfunction of the glymphatic system caused by TBI offers a novel and exiting explanation to this clinically observed phenomenon. The proposed model, although theoretical, could provide important mechanistic insights to the TBI-sleep-headache association.
KeywordsGlymphatic system Traumatic brain injury Concussion Headaches Sleep
Research in the authors’ labs is supported by funding from the NIH (AG054456, NS089709, JJI; K12HL133115, JP), the Paul G. Allen Family Foundation (JJI, MML), VA Career Development Award #IK2 BX002712 (MML), and GlaxoSmithKline (JJI).
Compliance with Ethical Standards
Conflict of Interest
Juan Piantino, Miranda M. Lim, Craig D. Newgard, and Jeffrey Iliff declare no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Interpretations and conclusions are those of the authors and do not represent the views of the U.S. Department of Veterans Affairs or the United States Government.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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