The effects of environmental light-dark changes on experimental mild traumatic brain injury

Uçar, Tanju; Özkaya, Yaşar Gül; Demır, Necdet; Gürer, İnanç Elif; Akyuz, Mahmut; Önal, Mehmet Zülküf

doi:10.1111/j.1600-0404.2005.00463.x

Cited by 8 publications

(11 citation statements)

References 46 publications

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“…However, it is possible that the pineal gland sustained damage due to the relatively uncontrolled nature of the weight-drop injury compared to the CCI. Additionally, some authors report MEL administered during night hours, while endogenous MEL levels are high, was effective whereas administration during daylight hours was not [25, 27]. More research into the pharmacology and pharmacokinetics of these compounds following the CCI and other TBI models would be useful.…”

Section: Discussionmentioning

confidence: 99%

Melatonin and minocycline for combinatorial therapy to improve functional and histopathological deficits following traumatic brain injury

Kelso

Scheff

et al. 2011

Neuroscience Letters

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The biochemical sequelae that follow traumatic brain injury (TBI) are numerous and affect many different brain functions at different points of time as the secondary cascades progress. The complexity of the resulting pathophysiology is such that a singular therapeutic intervention may not provide adequate benefit and a combination of drugs targeting different pathways may be needed. Two of the most widely studied injury mechanisms are oxidative stress and inflammation. Numerous studies have suggested that pharmacological agents targeting either of these pathways may produce an improvement in histological and functional outcome measures. We hypothesized that combining melatonin, a potent antioxidant, with minocycline, a bacteriostatic agent that also inhibit microglia, would provide better neuroprotection than either agent used alone. To test this hypothesis, we subjected anesthetized adult male rats to a 1.5 mm controlled cortical impact and administered melatonin or vehicle in the acute post-injury period followed by daily minocycline or vehicle injections beginning the following day in a 2×2 study design. The animals were allowed to recover for 5 days before undergoing Morris water maze (MWM) testing to assess cognitive functioning following injury. There was no significant difference in MWM performance between the vehicle, melatonin, minocycline, or combination treatments. Following sacrifice and histological examination for neuroprotection, we did not observe a significant difference between the groups in the amount of cortical tissue that was spared nor was there a significant difference in [ 3 H]-PK11195 binding, a marker for activated microglia. These results suggest that neither drug has therapeutic efficacy, however dosing and/or administration issues may have played a role.

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Section: Discussionmentioning

confidence: 99%

Melatonin and minocycline for combinatorial therapy to improve functional and histopathological deficits following traumatic brain injury

Kelso

Scheff

et al. 2011

Neuroscience Letters

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“…Melatonin is also involved in the regulation of other systems such as the pain system. In fact, the antinociceptive effect of melatonin has been demonstrated in animal models of acute pain (Li et al 2005;Ucar et al 2005;Elmegeed et al 2007), inflammatory pain (Arreola-Espino et al 2007), and neuropathic pain (Ulugol et al 2006). Preliminary studies in humans have shown melatonin effects on some pain syndromes, especially fibromyalgia (Citera et al 2000) and acute postoperative pain (Acil et al 2004;Caumo et al 2009).…”

Section: Introductionmentioning

confidence: 95%

Effect of exogenous melatonin administration on pain threshold in exercise trained rats under light-induced functional pinealectomy

Özkaya

Seyran

Hindistan

et al. 2014

Biological Rhythm Research

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Exercise-induced hypoalgesia (EIH) typically reported during and/or following exercise, but less is known the mechanisms responsible for EIH. Previous reports suggest that melatonin plays a role in pain modulation. In this study, we investigated the role of melatonin on pain threshold at rest, and following exercise in both sedentary and exercise trained rats under light-induced functional pinealectomy. Male wistar rats were assigned to one of four groups: sedentary control (C), sedentary pinealectomized (Px), exercise trained (T), and trained under pinealectomy (T-Px) groups. Exercise trained groups were subjected to eight weeks of motor-driven treadmill exercise. C and T groups exposed to normal light/dark cycle (12:12-h light/dark cycle) and Px and T-Px rats exposed to continuous light for eight weeks. Hot-plate test was repeated before and after melatonin injection and paw withdrawal latencies were recorded as pain threshold. Acute exercise resulted increased pain threshold in all groups. Animals in T group had significantly highest pain thresholds compared with other groups, and pinealectomy resulted decreased pain threshold in trained animals both at rest, and following exercise. Pain threshold in T-Px group was found to be increased after melatonin administration. Our findings support the hypothesis that melatonin plays a role on hypoalgesic response in exercise-trained rats.

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“…There is a dearth of research on improving sleep and reversing the negative effects of sleep disruption on homeostasis in critically‐ill patients. Melatonin is an agent with the capacity of entraining of circadian rhythms (chronobiotic effect) as well as having anti‐insomnia effects and neuroprotective actions [3, 73]. These actions have been demonstrated in humans by clinical trials and in experimental animal models [71, 74].…”

Section: Craniocerebral Trauma and Sleepmentioning

confidence: 99%

“…(c) CCT reportedly alters endogenous pineal melatonin secretion during the acute post‐traumatic period. These disturbances are characterized by the absence of the normal melatonin circadian rhythm [3, 71]. In addition to its protective action as an antioxidant in the brain, the general opinion is that melatonin is also a synchronizer of circadian rhythms [107].…”

Section: Benefits Of Melatonin In the Therapeutic Treatment Of Patienmentioning

confidence: 99%

“…Numerous pathophysiological mechanisms have been postulated to explain the progressive tissue damage produced by secondary injuries (free radical generation, neuroinflammatory response, adhesion molecule generation, cytokine and chemokine production and infections, among others) [1, 2]. Thus, several pharmacological therapies have been developed in an attempt to limit these injuries [2, 3].…”

Section: Introductionmentioning

confidence: 99%

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The potential of melatonin in reducing morbidity–mortality after craniocerebral trauma

Maldonado

Murillo-Cabezas

Terrón

et al. 2006

Journal of Pineal Research

172

149

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: Craniocerebral trauma (CCT) is the most frequent cause of morbidity–mortality as a result of an accident. The probable origins and etiologies are multifactorial and include free radical formation and oxidative stress, the suppression of nonspecific resistance, lymphocytopenia (disorder in the adhesion and activation of cells), opportunistic infections, regional macro and microcirculatory alterations, disruptive sleep–wake cycles and toxicity caused by therapeutic agents. These pathogenic factors contribute to the unfavorable development of clinical symptoms as the disease progresses. Melatonin (N‐acetyl‐5‐methoxytryptamine) is an indoleamine endogenously produced in the pineal gland and in other organs and it is protective agent against damage following CCT. Some of the actions of melatonin that support its pharmacological use after CCT include its role as a scavenger of both oxygen and nitrogen‐based reactants, stimulation of the activities of a variety of antioxidative enzymes (e.g. superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase), inhibition of pro‐inflammatory cytokines and activation–adhesion molecules which consequently reduces lymphocytopenia and infections by opportunistic organisms. The chronobiotic capacity of melatonin may also reset the natural circadian rhythm of sleep and wakefulness. Melatonin reduces the toxicity of the drugs used in the treatment of CCT and increases their efficacy. Finally, melatonin crosses the blood–brain barrier and reduces contusion volume and stabilizes cellular membranes preventing vasospasm and apoptosis of endothelial cells that occurs as a result of CCT.

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The effects of environmental light-dark changes on experimental mild traumatic brain injury

Cited by 8 publications

References 46 publications

Melatonin and minocycline for combinatorial therapy to improve functional and histopathological deficits following traumatic brain injury

Melatonin and minocycline for combinatorial therapy to improve functional and histopathological deficits following traumatic brain injury

Effect of exogenous melatonin administration on pain threshold in exercise trained rats under light-induced functional pinealectomy

The potential of melatonin in reducing morbidity–mortality after craniocerebral trauma

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