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Ischemia Model (ischemia + model)
Selected AbstractsStat4 and Stat6 signaling in hepatic ischemia/reperfusion injury in mice: HO-1 dependence of Stat4 disruption-mediated cytoprotectionHEPATOLOGY, Issue 2 2003Xiu-Da Shen Ischemia/reperfusion (I/R) injury remains an important problem in clinical organ transplantation. There is growing evidence that T lymphocytes, and activated CD4+ T cells in particular, play a key role in hepatic I/R injury. This study analyzes the role of signal transducer and activator of transcription 4 (Stat4) and Stat6 signaling in liver I/R injury. Using a partial lobar warm ischemia model, groups of wild-type (WT), T cell,deficient, Stat4-/Stat6-deficient knockout (KO) mice were assessed for the extent/severity of I/R injury. Ninety minutes of warm ischemia followed by 6 hours of reperfusion induced a fulminant liver failure in WT and Stat6 KO mice, as assessed by hepatocellular damage (serum alanine aminotransferase [sALT] levels), neutrophil accumulation (myeloperoxidase [MPO] activity) and histology (Suzuki scores). In contrast, T cell deficiency (nu/nu mice) or disruption of Stat4 signaling (Stat4 KO mice) reduced I/R insult. Unlike adoptive transfer of WT or Stat6-deficient T cells, infusion of Stat4-deficient T cells failed to restore hepatic I/R injury and prevented tumor necrosis factor , (TNF-,) production in nu/nu mice. Diminished TNF-,/Th1-type cytokine messenger RNA (mRNA)/protein elaborations patterns, along with overexpression of heme oxygenase-1 (HO-1),accompanied hepatic cytoprotection in Stat4 KO recipients. In contrast, HO-1 depression restored hepatic injury in otherwise I/R resistant Stat4 KOs. In conclusion, Stat4 signaling is required for, whereas Stat4 disruption protects against, warm hepatic I/R injury in mice. The cytoprotection rendered by Stat4 disruption remains HO-1,dependent. [source] The membrane attack complex (C5b-9) in liver cold ischemia and reperfusion injuryLIVER TRANSPLANTATION, Issue 8 2008Constantino Fondevila Activation of the complement cascade represents an important event during ischemia/reperfusion injury (IRI). This work was designed to investigate the role of the membrane attack complex (MAC; C5b-9) in the pathogenesis of hepatic IRI. Livers from B&W/Stahl/rC6(+) and C6(,) rats were harvested, stored for 24 hours at 4°C, and then transplanted [orthotopic liver transplantation (OLT)] to syngeneic recipients. There were 4 experimental groups: (1) C6(+),C6(+), (2) C6(+),C6(,), (3) C6(,),C6(+), and (4) C6(,),C6(,). At day +1, C6(,) OLTs showed decreased vascular congestion/necrosis, contrasting with extensive necrosis in C6(+) livers, that was independent of the recipient C6 status (Suzuki score: 7.2 ± 0.9, 7.3 ± 1.3, 4.5 ± 0.6, and 4.8 ± 0.4 for groups 1-4, respectively, P < 0.05). The liver function improved in recipients of C6(,) grafts (serum glutamic oxaloacetic transaminase: 2573 ± 488, 1808 ± 302, 1170 ± 111, and 1188 ± 184 in groups 1-4, respectively, P < 0.05). Intragraft macrophage infiltration (ED-1 immunostaining) and neutrophil infiltration (myeloperoxidase activity) were reduced in C6(,) grafts versus C6(+) grafts (P = 0.001); these data were confirmed by esterase staining (naphthol). The expression of proinflammatory interferon-,, interleukin-1,, and tumor necrosis factor messenger RNA/protein was also reduced in C6(,) OLTs in comparison with C6(+) OLTs. Western blot,assisted expression of proapoptotic caspase-3 was decreased in C6(,) OLTs versus C6(+) OLTs (P = 0.006), whereas antiapoptotic Bcl-2/Bag-1 was enhanced in C6(,) OLTs compared with C6(+) OLTs (P = 0.001). Terminal deoxynucleotidyl transferase,mediated dUTP nick end-labeling staining of apoptotic cells was enhanced (P < 0.05) in C6(+) OLTs compared with C6(,) OLTs. Thus, the terminal products of the complement system are essential in the mechanism of hepatic IRI. This is the first report using a clinically relevant liver cold ischemia model to show that local MAC inhibition attenuates IRI cascade in OLT recipients. Liver Transpl 14:1133,1141, 2008. © 2008 AASLD. [source] Dynamic contrast-enhanced MRI of muscle perfusion combined with MR angiography of collateral artery growth in a femoral artery ligation modelNMR IN BIOMEDICINE, Issue 8 2007Quido G. de Lussanet Abstract To assess the use of MRI for evaluating changes in muscle blood flow and number of collateral arteries, serial dynamic contrast-enhanced MRI (DCE-MRI) was combined with high-spatial-resolution contrast-enhanced MR angiography (MRA) in a peripheral ischemia model. The combined MRI (DCE-MRI and MRA) protocol was performed serially in 15 male rabbits at 2,h (day 0+), 7 days, and 21 days after femoral artery ligation. In the anterior tibial and soleus muscle, changes in resting muscle blood flow determined as the endothelial transfer coefficient (Ktrans) and arterial inflow delay from DCE-MRI and changes in the number of sub-millimeter sized collateral arteries as scored with MRA were measured. Directly after ligation, Ktrans in the anterior tibial muscle was reduced to 23% of that in the control limb, then recovered to 81% on day 7, and to 85 % on day 21. Ktrans in the soleus muscle recovered from a reduction to 63% on day 0+, to 85% on day 7, and to 90% on day 21. The number of collaterals around the ligated femoral artery increased from 1.1 on day 0+ to 4.2 on day 7, and 6.0 on day 21 in the ligated limb only. Combined DCE-MRI and MRA allows non-invasive serial monitoring of changes in muscle blood flow and growth of sub-millimeter sized collateral arteries in a rabbit femoral artery ligation model. Copyright © 2007 John Wiley & Sons, Ltd. [source] Neuroprotective effect of HT008-1, a prescription of traditional Korean medicine, on transient focal cerebral ischemia model in ratsPHYTOTHERAPY RESEARCH, Issue 8 2010Youngmin Bu Abstract HT008-1 is one of the prescriptions used in Traditional Korean Medicine for the treatment of mental and physical weakness. It is composed of Panax ginseng, Acanthopanax senticosus, Angelica sinensis and Scutellaria baicalensis, which have been reported to have various pharmacological effects on the central nervous system. The study investigated whether HT008-1 has neuroprotective effects in a focal cerebral ischemia rat model. Stroke was induced in rats by 2,h of middle cerebral artery occlusion (MCAo) followed by 22,h of reperfusion. HT008-1 (30, 100 and 300,mg/kg) and the component herbs (300,mg/kg) were administered orally twice at 0 and 2,h after ischemia. Oral administration of 300,mg/kg HT008-1 reduced brain infarction by 45.7%, prolonged the latency time by 24.8% in the rotarod test, and enhanced the score by 17.0% in the balance beam test. Only P. ginseng and S. baicalensis showed protective effects, and HT008-1 showed a greater effect than its component herbs. HT008-1 down-regulated the COX-2 and OX-42 expression in the penumbra region. In conclusion, the results show that HT008-1 may be effective in a rat stroke model by an antiinflammatory mechanism and may improve sensory-motor function by reducing damage in the cortex and caudoputamen. Copyright © 2010 John Wiley & Sons, Ltd. [source] Nitric oxide and cGMP protect the retina from ischemia and mediate somatostatin's neuroprotective effectsACTA OPHTHALMOLOGICA, Issue 2009K THERMOS Purpose The neuropeptide somatostatin has been shown to modulate retinal circuitry by activating its receptors (sst1-sst5) found in retinal neurons and to influence the levels of other neuroactive substances such as nitric oxide (NO) and cGMP. In addition, it displays neuroprotective properties against retinal chemical ischemia and excitotoxicity. In another paradigm, somatostatin was shown to protect cortical cultures against NMDA induced neuronal death via a cGMP mechanism. These findings led us to investigate whether NO and/or cGMP could protect the retina from ischemia, and possibly underlie somatostatin's neuroprotective actions. Methods A model of chemical ischemia was employed in rat retina in order to examine the neuroprotective effects of arginine, the substrate of nitric oxide synthase (NOS), and a number of NO donors. Subsequently, blockade of NOS and guanylyl cyclase in the presence of somatostatin receptor (sst2) agonists was attempted to investigate the role of NO/cGMP in somatostatin's protection of the retina in the chemical ischemia model and in a model of AMPA induced excitotoxicity. Results The NO donors SIN-1 and NONOate and 8-Br-cGMP protected the retina in a concentration-dependent manner, as shown by ChAT immunoreactivity and TUNEL staining. L-cysteine (the peroxynitrite scavenger) partially reduced the SIN-1 protective effect. NOS and guanyl cyclase inhibitors reversed the protective effect of sst2 agonists in the chemical ischemia and excitotoxicity model. Conclusion NO/peroxynitrite and cGMP appear to be important mediators in the protection of the retina from chemical ischemia. The NO/sGC/cGMP pathway is involved in the neuroprotective effects of the sst2 ligands in the same model and against AMPA excitotoxic insults. [source] | ||||||||||