RESUMEN
BACKGROUND AND PURPOSE: The present study was performed to determine the role of alpha4 (CD49d), a member of the integrin family of adhesion molecules, in ischemic brain pathology. METHODS: Male spontaneously hypertensive rats (SHR) or Sprague-Dawley rats underwent 60-minute middle cerebral artery occlusion (MCAO) followed by 23-hour reperfusion. Animals were injected intravenously with 2.5 mg/kg anti-rat alpha4 antibody (TA-2) or isotype control antibody (anti-human LFA-3 IgG(1), 1E6) 24 hours before MCAO. Infarct volume was quantified by staining of fresh tissue with tetrazolium chloride and myeloperoxidase activity measured in SHR tissue homogenates 24 hours after MCAO. In SHR, mean arterial blood pressure was recorded before and after MCAO in animals treated with TA-2 and 1E6. Fluorescence-activated cell sorting analysis was performed on peripheral blood leukocytes before and after MCAO. RESULTS: TA-2 treatment significantly reduced total infarct volume by 57.7% in normotensive rats (1E6, 84.2+/-11.5 mm(3), n=17; TA-2, 35.7+/-5.9 mm(3), n=16) and 35.5% in hypertensive rats (1E6, 146.6+/-15.5 mm(3), n=15; TA-2, 94.4+/-25.8 mm(3), n=11). In both strains, TA-2 treatment significantly reduced body weight loss and attenuated the hyperthermic response to MCAO. In SHR, treatment with TA-2 significantly reduced brain myeloperoxidase activity. Resting mean arterial blood pressure was unaffected by treatment. Leukocyte counts were elevated in TA-2-treated rats. Fluorescence-activated cell sorting analysis demonstrated the ability of TA-2 to bind to CD3+, CD4+, CD8+, and CD11b+ cells in both naive animals and after MCAO. CONCLUSIONS: These data demonstrate that inhibition of alpha4 integrin can protect the brain against ischemic brain injury and implicate endogenous alpha4 integrin in the pathogenesis of acute brain injury. The mechanism by which alpha4 integrin inhibition offers cerebroprotection is independent of blood pressure modulation and is likely due to inhibition of leukocyte function.
Asunto(s)
Antígenos CD/metabolismo , Infarto Cerebral/prevención & control , Ataque Isquémico Transitorio/metabolismo , Animales , Anticuerpos/farmacología , Antígenos CD/inmunología , Antígenos CD/farmacología , Presión Sanguínea/efectos de los fármacos , Temperatura Corporal/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Encéfalo/enzimología , Encéfalo/patología , Moléculas de Adhesión Celular/antagonistas & inhibidores , Moléculas de Adhesión Celular/inmunología , Moléculas de Adhesión Celular/metabolismo , Infarto Cerebral/etiología , Infarto Cerebral/metabolismo , Infarto Cerebral/patología , Modelos Animales de Enfermedad , Citometría de Flujo , Infarto de la Arteria Cerebral Media/complicaciones , Integrina alfa4 , Ataque Isquémico Transitorio/etiología , Ataque Isquémico Transitorio/inmunología , Ataque Isquémico Transitorio/patología , Recuento de Leucocitos , Leucocitos/citología , Leucocitos/efectos de los fármacos , Leucocitos/inmunología , Masculino , Peroxidasa/metabolismo , Ratas , Ratas Endogámicas SHR , Ratas Sprague-Dawley , Reproducibilidad de los ResultadosRESUMEN
Gastric perforation due to blunt trauma is rare, especially in children. The authors present a case of complete transection of the stomach in a 10-year-old boy who was thrown across the steel back of a seat in a school bus. Associated injuries included hematoma, a torn spleen, a seromuscular tear of the duodenojejunal flexure and complete transection of the pancreas and rectus abdominis muscle. The boy's postoperative course was complicated by the development of peritonitis with abscess formation and a pancreatic fistula. To the author's knowledge this is The first case of complete transection of the stomach, due to blunt trauma reported in the English literature.