Sleep-Wake Disturbances in Mild Traumatic Brain Injury: Meta analysis of Literature and Modeling of Cerebral Tissue Vulnerability

Abstract

Sleep disturbance is a frequent complaint for patients with mild traumatic brain injury (mTBI), it can prolong recovery, and the oxidative stress from lack of sleep could worsen other secondary damages of mTBI. The common types of sleep disturbance of mTBI include insomnia, daytime sleepiness, and obstructive sleep apnea. Conventional imaging often fails to detect any abnormalities in mTBI, and the etiology of sleep disturbance is still unclear. Based on the analysis of current published neurobiological and imaging literature, multiple factors could play a role leading to sleep disturbance in mTBI, however, we have focused on the diencephalon, melatonin and serotonin. We constructed a hypothesis that sleep disturbance may be caused by increased tau protein and decreased serotonin consequent to the dynamic load to pineal gland and hypothalamus by cerebrospinal fluid (CSF) during and after mild head trauma. A geometric model supporting this is under preparation in analogy with Alzheimer’s progression in less actives and Parkinson’s cases with upper body rigidity. In both situations CSF dynamics is abnormal and tau protein increases while serotonin/melatonin levels drop. Our model of impaired circulation of CSF leading to inefficient transportation of sleep-related protein, and excessive encounter of vulnerable tissues (Pineal gland and Hypothalamus for example) with reactive oxygen species due to abnormal CSF dynamics may contribute to dysfunction of sleep governing neuron