Abstract | OBJECTIVE: DESIGN: Randomized experiment. SETTING: Research laboratory at a university hospital. SUBJECTS: Male Sprague-Dawley rats (n = 215). INTERVENTIONS: MEASUREMENT AND MAIN RESULTS: Brain tissue nitrites, phosphorylation level of extracellular signal-regulated kinases, and c-jun N-terminal kinases; and expression of active caspase-3, tumor necrosis factor-α, BAX, and Bcl-2 as well as serum levels of interleukin-6, high mobility group box-1, interleukin-10, and brain histologic damage were evaluated 24 or 48 hrs after the insult. Sensorimotor orientation and limb use were evaluated at day 7 and learning and memory at days 23-30 after injury. Posttraumatic treatment every 12 hrs with the melanocortin analog [Nle, D-Phe]-α- melanocyte-stimulating hormone (starting 3 or 6 hrs after injury) inhibited traumatic brain injury-induced upregulation of nitric oxide synthesis, phosphorylation level of extracellular signal-regulated kinases, phosphorylation level of c-jun N-terminal kinases, and active caspase-3; reduced expressions/levels of tumor necrosis factor-α, BAX, interleukin-6, and high mobility group box-1; and increased those of Bcl-2 and interleukin-10. These molecular changes were associated with a reduction in brain tissue damage, as highlighted by histopathological findings and improved functional recovery. Pretreatment with the melanocortin MC4 receptor antagonist HS024 abated the positive effects of [Nle, D-Phe]-α- melanocyte-stimulating hormone. CONCLUSIONS:
|
Authors | Alessandra Bitto, Francesca Polito, Natasha Irrera, Margherita Calò, Luca Spaccapelo, Herbert R Marini, Daniela Giuliani, Alessandra Ottani, Mariagrazia Rinaldi, Letteria Minutoli, Salvatore Guarini, Francesco Squadrito, Domenica Altavilla |
Journal | Critical care medicine
(Crit Care Med)
Vol. 40
Issue 3
Pg. 945-51
(Mar 2012)
ISSN: 1530-0293 [Electronic] United States |
PMID | 22036855
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Retracted Publication)
|
Chemical References |
|
Topics |
- Animals
- Brain Injuries
(drug therapy, prevention & control)
- Male
- Melanocortins
(therapeutic use)
- Rats
- Rats, Sprague-Dawley
- Recovery of Function
- Time Factors
|