Changes in endogenous daytime melatonin levels after aneurysmal subarachnoid hemorrhage - Preliminary findings from an observational cohort study.

Introduction: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with early and delayed brain injury due to several underlying and interrelated processes, which include inflammation, oxidative stress, endothelial, and neuronal apoptosis. Treatment with melatonin, a cytoprotective neurohormone with anti-inflammatory, anti-oxidant and anti-apoptotic effects, has been shown to attenuate early brain injury (EBI) and to prevent delayed cerebral vasospasm in experimental aSAH models. Less is known about the role of endogenous melatonin for aSAH outcome and how its production is altered by the pathophysiological cascades initiated during EBI. In the present observational study, we analyzed changes in melatonin levels during the first three weeks after aSAH.
Materials and Methods: Daytime (from 11:00 am to 05:00 pm) melatonin levels were measured by enzyme-linked immunosorbent assay (ELISA) in serum samples obtained from 30 patients on the day of aSAH onset (d ₀ ) and in five pre-defined time intervals during the early (d _1-4 ), critical (d _5-8 , d _9-12 , d _13-15 ) and late (d _16-21 ) phase. Perioperative daytime melatonin levels determined in 30 patients who underwent elective open aortic surgery served as a control for the acute effects of surgical treatment on melatonin homeostasis.
Results: There was no difference between serum melatonin levels measured in the control patients and on the day of aSAH onset (p = 0.664). However, aSAH was associated with a sustained up-regulation that started during the critical phase (d _9-12 ) and progressed to the late phase (d _16-21 ), during which almost 80% of the patients reached daytime melatonin levels above 5 pg/ml. In addition, subgroup analyses revealed higher melatonin levels on d _5-8 in patients with a poor clinical status on admission (p = 0.031), patients with anterior communicating artery aneurysms (p = 0.040) and patients without an external ventricular drain (p = 0.018), possibly pointing to a role of hypothalamic dysfunction.
Conclusion: Our observations in a small cohort of patients provide first evidence for a delayed up-regulation of circulatory daytime melatonin levels after aSAH and a role of aneurysm location for higher levels during the critical phase. These findings are discussed in terms of previous results about stress-induced melatonin production and the role of hypothalamic and brainstem involvement for melatonin levels after aSAH.
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