Article
Minocycline reduces early brain injury following subarachnoid hemorrhage in rats
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Published: | May 13, 2014 |
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Objective: Early brain injury following aneurysmal subarachnoid hemorrhage (SAH) represents the most important cause of morbidity and mortality. The underlying injury mechanisms are not completely clarified. The amount of blood released during SAH correlates with the occurrence of delayed cerebral ischemia, secondary neurological deficits, and poor clinical outcome. Furthermore, inflammatory processes are likely to play an important role in the pathogenesis of early brain injury after SAH. The purpose of this study was to investigate the role of inflammation and subarachnoid hemoglobin in early brain injury following SAH and to examine the effect of minocycline.
Method: SAH was induced in Sprague-Dawley rats using the endovascular filament model (n=96). The extent of SAH was evaluated using a modified grading system of Sugawara et al. (2008). Sham-operated control rats underwent an identical procedure without vessel perforation (n=12). Minocycline was administered intraperitoneally (45 mg/kg, n=46). Animals were sacrificed at 3 h, 6 h, Day 1 and 3 following SAH, and ipsilateral frontobasal part of the brain was examined by Western blot and immunohistochemistry.
Results: HO-1 expression was significantly increased 24 h following the induction of SAH (p<0.001). The brain water content (BWC) of the ipsilateral hemisphere was markedly elevated (p<0.05) and accompanied by an increased expression of IL1-beta and TNF-alpha. Early therapy with minocycline effectively reduced BWC (p<0.05) and expression of inflammatory cytokines (p<0.001).
Conclusions: These results suggest that a high amount of subarachnoid hemoglobin and iron in the adjacent brain tissue as well as early immunological processes cause secondary cerebral injury leading to neuronal cell death. Minocycline effectively reduced iron toxicity and/or inflammation-related brain injury. Therefore, it may represent a potential therapeutic agent for SAH.