Glymphatic System Dysfunction in Mild Traumatic Brain Injury

Abstract

To assess the clinical role of the glymphatic system in mild traumatic brain injury (mTBI) and post-concussive syndrome (PCS). Clinical manifestations of mTBI, or concussion, involve a wide array of cognitive, behavioral, and mechanical impairments that commonly spontaneously resolve within weeks. When these symptoms persist, it defines a class of mTBI known as post-concussive syndrome. A multifaceted approach for diagnosing concussion and PCS, heavily reliant on a neurocognitive screening, has become the standard in suspected cases. Conventional imaging protocols are occasionally implemented for exclusion of structural injury, rarely revealing substantial evidence in otherwise uncomplicated mTBI. A CNS-specific lymphatic network, termed glymphatic, has shown to play a critical role in immune surveillance and drainage of cellular debris. Moreover, recent evidence points to glymphatic dysfunction in TBI, including mild cases, as its anatomical layout becomes better understood. Here, we review the current literature on glymphatic function and imaging modalities, with an emphasis on implications in mTBI. Literature was compiled primarily using various keyword searches (glymphatic + imaging, meningeal lymphatics, glymphatic + concussion, etc.) via Pubmed and the NIH/NLM archive. Inclusion criteria involved limiting to studies on human patients or tissue. The glymphatic system displays critical function in healthy patients and in disease, with activity that suggests a diurnal sleep-cycle. Advanced imaging methodologies, most notably, the use of various MRI techniques, have identified impairments in meningeal lymphatic dysfunction in TBI, however, the clinical application of glymphatic imaging has yet to be well-studied and shows challenges in providing definitive data. Nonetheless, the potential for glymphatic imaging to expand our understanding of mTBI and PCS warrants further investigation. Anatomical and functional properties of the glymphatic network make an appealing target for concussion diagnosis, observing recovery, and exposing impact-related microstructural injuries, however the implementation of imaging in a clinical setting has yet to be well-characterized.