Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increasing data provide support for the hypothesis that brain inflammation plays an important role in injury to developing white matter. In the present study, inflammatory responses in the neonatal rat brain were investigated following lipopolysaccharide (LPS) administration at postnatal day 5. LPS-induced brain injury was examined in brain sections 24 h, 3 and 9 days after LPS injection. White matter rarefaction was observed in 50% of the rat brains (three out of six) 24 h after LPS injection. Lateral ventricle enlargement was found in 100% (four out of four) and 89% (eight out of nine) of rat brains 3 and 9 days after LPS administration, respectively. White matter necrosis was found in three out of nine brains injected with LPS on P14. None of these injuries was observed in any control rat brains. No histological changes in gray matter were noted in the LPS-injected rat brain. Proinflammatory cytokines, tumor necrosis factor-alpha (TNFalpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6), and inducible nitric oxide synthase (iNOS) in the rat brain were greatly induced after LPS administration. Activated astrocytes and microglia/macrophages were found in the affected rat brains. Double-labeling showed that IL-1beta and iNOS expressing cells were microglia/macrophages. Injury to or delayed development of immature oligodendrocytes (OLs) was evident by decreased immunostaining for both O4 and O1 antibodies, markers for developing immature OLs, in the LPS-injected as compared to the control rat brain. LPS also resulted in hypomyelination, as indicated by reduced myelin basic protein (MBP) immunostaining in the P8 rat brain. Co-administration of IL-1 receptor antagonist (IL-1Ra) with LPS reduced brain injury by improving myelination and subsequent reduction of lateral ventricle enlargement. These results indicate that developing OLs may be the target cells for LPS-induced brain injury and inflammatory cytokines are possible mediators of LPS-induced brain injury.
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PMID:Disturbance of oligodendrocyte development, hypomyelination and white matter injury in the neonatal rat brain after intracerebral injection of lipopolysaccharide. 1258 26

Periventricular leukomalacia (PVL), the dominant form of brain injury in premature infants, is characterized by white matter injury (WMI) and is associated with cerebral palsy. The pathogenesis of PVL is complex and likely involves ischemia/reperfusion, free radical formation, excitotoxicity, impaired regulation of cerebral blood flow, a procoagulant state, and inflammatory mechanisms associated with maternal and/or fetal infection. Using an established animal model of human PVL, we investigated whether activated protein C (APC), an anti-coagulant factor with anti-inflammatory, anti-apoptotic, anti-oxidant, and cytoprotective activities, could reduce endotoxin-induced WMI in the developing rat brain. Intraperitoneal injections of lipopolysaccharide (LPS) (0.5 mg/kg body weight) were given at embryonic days 18 (E18) and 19 (E19) to pregnant Sprague-Dawley rats; control rats were injected with sterile saline. A single intravenous injection of recombinant human (rh) APC (0.2 mg /kg body weight) was given to pregnant rats following the second LPS dose on embryonic day 19 (E19). Reduced cell death in white matter and hypomyelination were shown on TUNEL and myelin basic protein (MBP) staining, respectively, on late postnatal days (P7) in APC-treated groups. There were significantly fewer TUNEL+nuclei in the periventricular WM in the APC+LPS group than in the untreated LPS group. Compared to the APC+LPS and control group, MBP expression was weak in the LPS group on P7, indicating endotoxin-induced hypomyelination in the developing rat brain. APC attenuated the LPS-induced protein expression of inflammatory cytokines, tumor necrosis factor-alpha, and interleukin-6, as evaluated by ELISA in neonatal rat brains. A single intraperitoneal injection of rhAPC (0.2 mg/kg body weight) to neonatal rats on P1 also had similar protective and anti-inflammatory effects against maternally administered LPS. Collectively, these data support the hypothesis that APC may provide protection against an endotoxin-evoked inflammatory response and WMI in the developing rat brain. Moreover, our results suggest that the possible use of APC in treatment of preterm infants and pregnant women with maternal or placental infection may minimize the risk of PVL and cerebral palsy.
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PMID:Activated protein C reduces endotoxin-induced white matter injury in the developing rat brain. 1764 74