Evaluation of late cognitive impairment and anxiety states following traumatic brain injury in mice: the effect of minocycline.
Comorbidity of cognitive and stress disorders is a common clinical sequel of traumatic brain injury (TBI) that is essentially determined by the site and severity of the insult, but also by the extent of the ensuing neuroinflammatory response. The present study sought to examine the late effects of closed-head TBI on memory function and anxiety in mice, in order to further examine the potential efficacy of an acute anti-inflammatory treatment with minocycline. The mouse model of closed-head injury by mechanical percussion was applied on 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. The Novel Object Recognition Test as well as the Elevated Plus Maze (EPM) and Elevated Zero Maze (EZM) tasks were employed to assess post-TBI memory and anxiety respectively. Our results revealed a recognition memory deficit that was significant up to at least 13 weeks post-TBI. However, neither EPM nor EZM revealed any alteration in post-TBI anxiety levels albeit some mild disinhibition. Most importantly, minocycline was able to attenuate the memory impairment in an effective and lasting manner, highlighting its therapeutic potential in TBI.
Laboratoire de Pharmacologie de la Circulation Cérébrale (EA 4475), Université Paris Descartes, Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France. eleni.siopi@etu.parisdescartes.fr
Eleni
E
Siopi
Gemma
G
Llufriu-Dabén
Francesca
F
Fanucchi
Michel
M
Plotkine
Catherine
C
Marchand-Leroux
Mehrnaz
M
Jafarian-Tehrani
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy* / Q000209:etiology; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D051379:Mice; D008911:Minocycline / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D008911:Minocycline