Minocycline Restores sAPPα Levels and Reduces the Late Histopathological Consequences of Traumatic Brain Injury in Mice

Traumatic brain injury (TBI) induces both focal and diffuse lesions that are concurrently responsible for the ensuing morbidity and mortality and for which no established treatment is available. It has been recently reported that an endogenous neuroprotector, the soluble form alpha of the amyloid precursor protein (sAPP alpha), exerts neuroprotective effects following TBI. However, the emergent post-traumatic neuroinflammatory environment compromises sAPP alpha production and may promote neuronal degeneration and consequent brain atrophy. Hence, the aim of this study was to examine the effects of the anti-inflammatory drug minocycline on sAPP alpha levels, as well as on long-term histological consequences post-TBI. The weight-drop model was used to induce TBI in mice. Minocycline or its vehicle were administered three times: at 5 min (90mg/ kg, i.p.) and at 3 and 9 h (45 mg/kg, i.p.) post-TBI. The levels of sAPP alpha, the extent of brain atrophy, and reactive gliosis were evaluated by ELISA, cresyl violet, and immunolabeling of GFAP and CD11b, respectively. Our results revealed a post-TBI sAPP alpha decrease that was significantly attenuated by minocycline. Additionally, corpus callosum and striatal atrophy, ventriculomegaly, astrogliosis, and microglial activation were observed at 3 months post-TBI. All the above consequences were significantly reduced by minocycline. In conclusion, inhibition of the acute phase of post-TBI neuroinflammation was associated with the sparing of sAPP alpha and the protection of brain tissue in the long-term, emphasizing the potential role of minocycline as an effective treatment for TBI.