Article

Sleep disturbance and melatonin levels following traumatic brain injury

School of Psychology and Psychiatry, Monash University, Victoria 3800, Australia.
Neurology (Impact Factor: 8.3). 05/2010; 74(21):1732-8. DOI: 10.1212/WNL.0b013e3181e0438b
Source: PubMed

ABSTRACT Sleep disturbances commonly follow traumatic brain injury (TBI) and contribute to ongoing disability. However, there are no conclusive findings regarding specific changes to sleep quality and sleep architecture measured using polysomnography. Possible causes of the sleep disturbances include disruption of circadian regulation of sleep-wakefulness, psychological distress, and a neuronal response to injury. We investigated sleep-wake disturbances and their underlying mechanisms in a TBI patient sample.
This was an observational study comparing 23 patients with TBI (429.7 +/- 287.6 days post injury) and 23 age- and gender-matched healthy volunteers on polysomnographic sleep measures, salivary dim light melatonin onset (DLMO) time, and self-reported sleep quality, anxiety, and depression.
Patients with TBI reported higher anxiety and depressive symptoms and sleep disturbance than controls. Patients with TBI showed decreased sleep efficiency (SE) and increased wake after sleep onset (WASO). Although no significant group differences were found in sleep architecture, when anxiety and depression scores were controlled, patients with TBI showed higher amount of slow wave sleep. No differences in self-reported sleep timing or salivary DLMO time were found. However, patients with TBI showed significantly lower levels of evening melatonin production. Melatonin level was significantly correlated with REM sleep but not SE or WASO.
Reduced evening melatonin production may indicate disruption to circadian regulation of melatonin synthesis. The results suggest that there are at least 2 factors contributing to sleep disturbances in patients with traumatic brain injury. We propose that elevated depression is associated with reduced sleep quality, and increased slow wave sleep is attributed to the effects of mechanical brain damage.

Download full-text

Full-text

Available from: Jennie Ponsford, Feb 28, 2015
1 Follower
 · 
162 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Numerous studies on the high prevalence of sleep disorders in individuals with traumatic brain injury (TBI) have been conducted in the past few decades. These disorders can accentuate other consequences of TBI, negatively impacting mood, exacerbating pain, heightening irritability, and diminishing cognitive abilities and the potential for recovery. Nevertheless, sleep is not routinely assessed in this population. In our review, we examined the selective screening criteria and the scientific evidence regarding screening for post-TBI sleep disorders to identify gaps in our knowledge that are in need of resolution. We retrieved papers written in the English-language literature before June 2012 pertinent to the discussion on sleep after TBI found through a PubMed search. Within our research, we found that sleep dysfunction is highly burdensome after TBI, treatment interventions for some sleep disorders result in favorable outcomes, sensitive and specific tests to detect sleep disorders are available, and the cost-effectiveness and sustainability of screening have been determined from other populations. The evidence we reviewed supports screening for post-TBI sleep dysfunction. This approach could improve the outcomes and reduce the risks for post-TBI adverse health and nonhealth effects (e.g., secondary injuries). A joint sleep and brain injury collaboration focusing on outcomes is needed to improve our knowledge.
    Sleep Medicine 09/2013; 14(12). DOI:10.1016/j.sleep.2013.07.009 · 3.10 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent studies have demonstrated that the human placenta is a novel source of adult stem cells. We have provided laboratory evidence that transplantation of these human placenta-derived cells in vitro and in vivo stroke models promotes functional recovery. However, the mechanisms underlying these observed therapeutic benefits of human placenta-derived cells unfortunately remain poorly understood. Here, we examined the expression of two discrete types of melatonin receptors and their roles in proliferation and differentiation of cultured human amniotic epithelial cells (AECs). Cultured AECs express melatonin receptor type 1A (MT1), but not melatonin receptor type 1B (MT2). The proliferation of cultured AECs was increased in the melatonin-treated group in a dose-dependent manner, and the viability of cultured AECs could be further enhanced by melatonin. Moreover, the viability of AECs significantly decreased with H(2) O(2) exposure, which was reversed by pretreatment with melatonin, resulting in increased cell survival rate and cell proliferation. Immunocytochemically, administration of melatonin significantly suppressed nestin proliferation, but enhanced TUJ1 differentiation of MT1-expressing AECs. Additional experiments incorporating antibody blocking and synergistic AEC-melatonin treatments further showed AEC therapeutic benefits via MT1 modulation. Finally, analysis of trophic factors revealed cultured AECs secreted VEGF in the presence of melatonin. These data indicate that melatonin by stimulating MT1 increased cell proliferation and survival rate while enhancing neuronal differentiation of cultured AECs, which together with VEGF upregulation, rendered neuroprotection against experimental in vitro models of ischemic and oxidative stress injury.
    Journal of Pineal Research 04/2011; 50(3):272-80. DOI:10.1111/j.1600-079X.2010.00837.x · 7.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The induction of oxidative stress and inflammation has been closely linked in traumatic brain injury (TBI). Transcriptional factors of signal transducers and activators of transcription (STAT) proteins are redox sensitive and participate in the regulation of cytokine signaling. Previous studies demonstrated that melatonin protects neurons through its antioxidative and anti-inflammatory effects in various neuropathological conditions. However, the effect of melatonin on STAT activity after TBI has not yet been explored. In this study, we used a controlled weight-drop TBI model and found that brain contusion induced oxidative stress (a decreased level of total glutathione and an increased ratio of oxidized glutathione to total glutathione), a reduction in STAT1 DNA-binding activity, and consequently neuronal loss in a contusion depth-dependent manner. A significant increased mRNA expression of suppressor of cytokine signaling (SOCS3), inducible nitric oxide synthetase (iNOS), and interleukine-6 (IL-6), but a decreased protein expression of protein inhibitor of activated STAT (PIAS1), was found 24 hr after brain contusion. SOCS3 and PIAS1 are endogenous negative regulators of STAT1. Moreover, the combination of intraperitoneal and local (presoaked in gelfoam and placed on the traumatic cortex) administration of melatonin had the most pronounced influence in inhibiting all effects except the PIAS1 downregulation induced by brain contusion. The results suggest that SOCS-3 upregulation and oxidative stress may contribute to the STAT1 inactivation after TBI. Melatonin protects neurons from TBI by reducing oxidative stress, STAT1 inactivation, and upregulation of SOCS-3 and pro-inflammatory cytokines.
    Journal of Pineal Research 04/2011; 51(2):233-45. DOI:10.1111/j.1600-079X.2011.00885.x · 7.81 Impact Factor