Minocycline restores sAPPα levels and reduces the late histopathological consequences of traumatic brain injury in mice.

Abstract

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 α of the amyloid precursor protein (sAPPα), exerts neuroprotective effects following TBI. However, the emergent post-traumatic neuroinflammatory environment compromises sAPPα 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 sAPPα 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 (90 mg/kg, i.p.) and at 3 and 9 h (45 mg/kg, i.p.) post-TBI. The levels of sAPPα, 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 sAPPα 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 sAPPα and the protection of brain tissue in the long-term, emphasizing the potential role of minocycline as an effective treatment for TBI.

• Authors: Eleni Siopi, Angelo H Cho, Shadi Homsi, Nicole Croci, Michel Plotkine, Catherine Marchand-Leroux, Mehrnaz Jafarian-Tehrani
• Journal: Journal of neurotrauma (J Neurotrauma) Vol. 28 Issue 10 Pg. 2135-43 (Oct 2011) ISSN: 1557-9042 [Electronic] United States
• PMID: 21770756 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Protein Precursor
• Anti-Bacterial Agents
• CD11b Antigen
• Neuroprotective Agents
• Minocycline

Topics

• Amyloid beta-Protein Precursor (metabolism)
• Animals
• Anti-Bacterial Agents (pharmacology)
• Brain Chemistry (drug effects)
• Brain Injuries (drug therapy, pathology)
• CD11b Antigen (metabolism)
• Cerebral Ventricles (pathology)
• Corpus Callosum (metabolism, pathology)
• Corpus Striatum (pathology)
• Enzyme-Linked Immunosorbent Assay
• Gliosis (pathology)
• Immunohistochemistry
• Male
• Mice
• Minocycline (pharmacology)
• Neuroprotective Agents