Traumatic brain injury (TBI) is a clinical emergency with a very high incidence, disability, and fatality rate. Minocycline, a widely used semisynthetic second-generation tetracycline antibiotic, has anti-inflammatory and bactericidal effects. However, minocycline has not been explored as a therapeutic drug in TBI and if effective, the related molecular mechanism is also unclear. In this study, we examined the neuroprotective effect and possible mechanism of minocycline, in mice TBI model by studying the trauma-related functional and morphological changes. Also, in vitro cell studies were carried out to verify the animal model data. We found that minocycline significantly improved the neurobehavioral score, inhibited apoptosis, repaired the blood-brain barrier, and reduced the levels of inflammatory factors Interleukin-6 and tumor necrosis factor-α in TBI mice. In vitro, upon oxygen and glucose deprivation, minocycline reduced the levels of cellular inflammatory factors and increased the levels of tight junction and adherens junction proteins, thereby significantly improving the cell viability. Moreover, Mino treatment prevented the loss of tight junction and adherens junction proteins which were markedly reversed by an ER stress activator (tunicamycin) both in vivo and in vitro. Our findings set an effective basis for the clinical use of Mino to treat Traumatic brain injury-induced neurological deficits.
Minocycline improves the recovery of nerve function and alleviates blood-brain barrier damage by inhibiting endoplasmic reticulum in traumatic brain injury mice model
