Minocycline effects on cerebral edema: relations with inflammatory and oxidative stress markers following traumatic brain injury in mice.
One of the severe complications following traumatic brain injury (TBI) is cerebral edema and its effective treatment is of great interest to prevent further brain damage. This study investigated the effects of minocycline, known for its anti-inflammatory properties, on cerebral edema and its respective inflammatory markers by comparing different dose regimens, on oxidative stress and on neurological dysfunction following TBI. The weight drop model was used to induce TBI in mice. The brain water content was measured to evaluate cerebral edema. Inflammatory markers were detected by ELISA (IL-1beta), zymography and Western blot (MMP-9). The oxidative stress marker (glutathione levels) and neurological function were measured by Griffith technique and string test, respectively. Minocycline was administered i.p. once (5 min), twice (5 min and 3 h) or triple (5 min, 3 h and 9 h) following TBI. The first dose of minocycline only varied (45 or 90 mg/kg), whereas the following doses were all at 45 mg/kg. The single and double administrations of minocycline reduced the increase of inflammatory markers at 6 h post-TBI. Minocycline also reduced cerebral edema at this time point, only after double administration and at the high dose regimen, although with no effect on the TBI-induced oxidized glutathione increase. The anti-edematous effect of minocycline persisted up to 24 h, upon a triple administration, and accompanied by a neurological recovery. In conclusion, we reported an anti-edematous effect of minocycline after TBI in mice according to a specific treatment regimen. These findings emphasize that the beneficial effects of minocycline depend on the treatment regimen following a brain injury.
Homsi
Shadi
S
Laboratoire de Pharmacologie de la Circulation Cérébrale (EA 2510), Université Paris Descartes, Faculté des Sciences Pharmaceutiques et Biologiques, 4, avenue de l'Observatoire, 75006 Paris, France.
Federico
Fabiola
F
Croci
Nicole
N
Palmier
Bruno
B
Plotkine
Michel
M
Marchand-Leroux
Catherine
C
Jafarian-Tehrani
Mehrnaz
M
D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D015153:Blotting, Western; D001834:Body Water; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D001930:Brain Injuries / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008911:Minocycline / Q000627:therapeutic use*; D009460:Neurologic Examination; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology
D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D020780:Matrix Metalloproteinase 9; D008911:Minocycline