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Minocycline Protects Against NLRP3 Inflammasome-Induced Inflammation and P53-Associated Apoptosis in Early Brain Injury After Subarachnoid Hemorrhage

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Abstract

Minocycline has beneficial effects in early brain injury (EBI) following subarachnoid hemorrhage (SAH); however, the molecular mechanisms underlying these effects have not been clearly identified. This study was undertaken to determine the influence of minocycline on inflammation and neural apoptosis and the possible mechanisms of these effects in early brain injury following subarachnoid hemorrhage. SAH was induced by the filament perforation model of SAH in male Sprague–Dawley rats. Minocycline or vehicle was given via an intraperitoneal injection 1 h after SAH induction. Minocycline treatment markedly attenuated brain edema secondary to blood-brain barrier (BBB) dysfunction by inhibiting NLRP3 inflammasome activation, which controls the maturation and release of pro-inflammatory cytokines, especially interleukin-1β (IL-1β). Minocycline treatment also markedly reduced the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cells. To further identify the potential mechanisms, we demonstrated that minocycline increased Bcl2 expression and reduced the protein expression of P53, Bax, and cleaved caspase-3. In addition, minocycline reduced the cortical levels of reactive oxygen species (ROS), which are closely related to both NLRP3 inflammasome and P53 expression. Minocycline protects against NLRP3 inflammasome-induced inflammation and P53-associated apoptosis in early brain injury following SAH. Minocycline’s anti-inflammatory and anti-apoptotic effect may involve the reduction of ROS. Minocycline treatment may exhibit important clinical potentials in the management of SAH.

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Acknowledgments

This study was supported by the Scientific and Technological Project of Zhejiang Province (2013C33138) and the Qianjiang rencai project (2013R10029).

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    Authors and Affiliations

    1. Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China

      Jianru Li, Jingsen Chen, Hangbo Mo, Jingyin Chen, Cong Qian, Feng Yan, Chi Gu, Lin Wang & Gao Chen

    2. Department of Neurosurgery, Hangzhou First People’s Hospital, Nanjing Medical University, Hangzhou, China

      Qiang Hu

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    1. Jianru Li
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    Correspondence to Gao Chen.

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    Jianru Li, Jingsen Chen and Hangbo Mo contributed equally to this work.

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    Li, J., Chen, J., Mo, H. et al. Minocycline Protects Against NLRP3 Inflammasome-Induced Inflammation and P53-Associated Apoptosis in Early Brain Injury After Subarachnoid Hemorrhage. Mol Neurobiol 53, 2668–2678 (2016). https://doi.org/10.1007/s12035-015-9318-8

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