RESUMEN
Expression of angiotensin II (Ang II) and its receptors (AT1/AT2) is undetected in the mature microglia in normal brain. We report here that the immunoexpression of Ang II and AT1/AT2 was altered in activated microglia notably at 1 week in rats subjected to middle cerebral artery occlusion (MCAO). Immunolabeled activated microglia were widely distributed in the infarcted cerebral tissue after MCAO. By enzyme immunoassay, Ang II protein expression levels of the ischemic tissues were decreased drastically at 12 h after ischemia, then rose rapidly at 3 days and 1 week after MCAO when compared with the control. On the other hand, AT1 and AT2 receptor mRNA and protein levels were up-regulated after MCAO, peaking at 12 h, but declined thereafter. Expression of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) mRNA and protein levels was concomitantly increased. Edaravone significantly suppressed Ang II and AT1/AT2 receptor expression as well as that of TNF-α and IL-1ß suggesting that microglia-derived Ang II can act through an autocrine manner via its receptor that may be linked partly to the production of proinflammatory cytokines. We conclude that neuroinflammation in MCAO may be attenuated by Edaravone which acts through suppression of expression of Ang II and its receptors and proinflammatory cytokines in activated microglia.
Asunto(s)
Angiotensina II/metabolismo , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Microglía/metabolismo , Microglía/patología , Receptor de Angiotensina Tipo 1/metabolismo , Receptor de Angiotensina Tipo 2/metabolismo , Envejecimiento/metabolismo , Animales , Antipirina/análogos & derivados , Antipirina/farmacología , Western Blotting , Isquemia Encefálica/genética , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Edaravona , Regulación de la Expresión Génica/efectos de los fármacos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Masculino , Microglía/efectos de los fármacos , Transporte de Proteínas/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Receptor de Angiotensina Tipo 1/genética , Receptor de Angiotensina Tipo 2/genética , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE: To set up a classification standard of mild and moderate traumatic brain injury, for the purpose of reliable data comparison derived from different laboratories. METHODS: Traumatic brain injury (TBI) in rats was prepared by using a metallic pendulum-striker device. After injury, five variable parameters including the time of apnea and the areflexia, time of corneal reflex, external auditory canal stung reaction, body-righting reflex and needling reaction were determined and scored by using rat coma criterion. These data were judged and classified into mild and moderate head injury by brain patho-anatomy changes. Then the data were used to set up a multivariate discriminate equation. RESULTS: The distinguished probability of mild and moderate TBI according to actual direct measured value and the criterion were 88.9% and 91.9%, respectively. CONCLUSION: This method is able to classify mild and moderate TBI in rats.