title: Minocycline restores olfactory bulb volume and olfactory behavior after traumatic brain injury in mice.
abstract: Permanent olfactory dysfunction can often arise after traumatic brain injury (TBI) and while one of the main causes is the immediate loss of neurons in the olfactory bulb (OB), the emergent neuroinflammatory environment following TBI may further promote OB deterioration. Therefore, we examined the effects of acute anti-inflammatory treatment with minocycline on post-TBI olfactory behavior and on OB surface. The mouse model of closed-head injury by mechanical percussion was applied to anesthetized Swiss mice. The treatment protocol included three injections of minocycline (i.p.) at 5 min (90 mg/kg), 3 h, and 9 h (45 mg/kg) post-TBI. An olfactory avoidance test was run up to 12 weeks post-TBI. The mice were then sacrificed and their OB surface was measured. Our results demonstrated a post-TBI olfactory behavior deficit that was significant up to at least 12 weeks post-TBI. Additionally, substantial post-TBI OB atrophy was observed that was strongly correlated with the behavioral impairment. Minocycline was able to attenuate both the olfactory lesions and corresponding functional deficit in the short and long term. These results emphasize the potential role of minocycline as a promising neuroprotective agent for the treatment of TBI-related olfactory bulb lesions and deficits.
authors.affiliation: Laboratoire de Pharmacologie de la Circulation Cérébrale (EA 4475), Université Paris Descartes, Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
authors.forename: Eleni
authors.initials: E
authors.lastname: Siopi
authors.forename: Silvia
authors.initials: S
authors.lastname: Calabria
authors.forename: Michel
authors.initials: M
authors.lastname: Plotkine
authors.forename: Catherine
authors.initials: C
authors.lastname: Marchand-Leroux
authors.forename: Mehrnaz
authors.initials: M
authors.lastname: Jafarian-Tehrani
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008911:Minocycline / Q000008:administration & dosage / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000857:Olfaction Disorders / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D009830:Olfactory Bulb / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology*; D012903:Smell / Q000187:drug effects / Q000502:physiology*
chemical_list: D018696:Neuroprotective Agents; D008911:Minocycline