Early hematoma enlargement and delayed clotlysis contribute to brain injury after intracerebral bemorrhage (ICH). We investigated hematoma growth, clotlysis, and brain edema formation in patients with spontaneous ICH. A total of 17 spontaneous ICH patients who received regular med-ication were ehosen for this study. All patients had their first CT scan within 5 hours of onset of symptoms (day 0). The patients then un-derwent second, third, and fourth CT scans at 1, 3, and 10 days later. measured Hematoma entargement was defined as a>33% increase in volurne. Relative brain edema volume=absoute brain edema volume/hematoma size Hematoma enlargermaent occurted in 4 of the 17 ICH paticets (24%) within the first 24 hours. The hematoma sizes However, both absolute and relative brain edema increased gradually with time (P<0.01). These Results suggest that delayed brain edema following ICH may Result From hematima lysis. This Study also shows tha carly hematoma cnlargement occurs in Cbinese patients with ICH Reduc-ing early hematoma growth and limiting clot lysis-induced brain toxicity could be potential therapies for ICH.

Our previous study demonstrated that the inhibition of interleukin-1β (IL-1β) reduces ischemic brain injury; how-ever, the molecular mechaism of the action of IL-1 in cerebralischemia is unclear. We are investigating cur-rently the role of NFkB during focal cerebral ischemia, usingmutant mice deficient in the interleukin-1 convert-ing enzyme gene (ICE KO) in a middle cerebral artery ocfclusion (MCAO) model. Adult male ICE KO and wild-type mice (n=120) undervent up to 24 hu of permanent MCAO. Cytoplasmic phospho-NFkB/p65 expression in ischemic brain was examined using Western Blot analy-sis and immunohistochemistry. NFkb DNA-binding ac-tivity was detected using electrophoretic mobility shift assay (EMSA). furthermore, ICAM-1 expression was ex-amined in both the ICE KO and wild-type mice (WT). Western blot analysis and immunostaining showed that the level of cytosolic phosphorylated NFkB/p65 in-creased after 2 and 4 hr of MCAO in WT mice; however, NFkB/p65 was significantly reduced after MCAO in the ICE KO mice (p<0.05). EMSA showed that NFkB DNA-binding activity increased after MCAO in WT mice;but this effect was reduced in the ICE KO mice. The number of ICAM-1-positive cessels in the ischemic hemiwphere was greatly attenuated in the ICE KO mice (p<0.05). which paralleled the results of immunohistochemistry. Our results demonstrate that NFkB phosphorylation is reduced in ICE KO mice, suggesting that ICE or IL-1 are involved in early NFkB phosphorylation. Because cere-bral ischemia induced infarction is significantly reduced in ICE KO mice, we conclude that early NFkB phosphorylation plays a disruptive role in the ischemic process.

Object The mechnisms involved in brain edema formation following intracerebral hemorrhage (ICH) have not been fully elueidated. The authous have found that red blood cell lysis plays an important role in edema develop-ment after ICH. In the present study, they soughy to detennine whether degradation produets of hemoglobin cause brain edema. Methods Hemoglobin, hemin, bilirubin, of FeCL2, were in fused with stereotactie guidance into the right basal gan-glia of Sprague-Dawley rats. The animals 24 hours later to determine brain water and ion contents. Wesern blot analysis and immunohistochemistry were applied for heme oxygenase-1 (HO-1) measurement. The effects of an HO inhibitor, tin-protoporphyrin (SnPP), and the iron chelator deferoxamine, on hemoglobin-induced brain edema were also examined. Intracerebral infusion of hemoglobin, hemin, bilirubin, or FeCl2 cansed an inerease in brain water content at 24 hours, The HO-1 was upregulated after hemoglobin infusion and HO inhibition by Snpp-attenuated hemoglobin in duced edema. Brain edema induced by hemoglobin was so attenuated by the intraperitoneal injection of 500mg/kg deferoxamine. Conchusions Hemoglobin causes brain edema. at least in part, through its degradation products. Limiting hemo-globin degradation coupled with the use o9f iron chelator may be a novel therapeutie approach to limit brain edema after ICH.

The present study is to determine the effect of mild hypothermia (MHT) on the release of glutamate and glycine in rats subjected to middle cerebral artery occlusion and reperfusion. The relationship between amino acid efflux and brain infarct volume was compared in different periods during MHT. Reversible middle cerebral artery occlusion was performed in Sprague-Dawley rats using a suture model. The rats were divided into four gruops including (1) MHT during ischemia (MHTi), (2) MHT during reperfusion (MHTr), (3) MHT during ischemia and reperfusion (MHTi+r), and (4) a normothermic group (NT). Extracellular concentrations of glutamate and glycine in the cortex and striatum were monitored using in vivo microdialysis and analyzed using high-performance liquid chromatography. Morphometric for infarct volume were performed using 2, 3.5-triphenyltetrazolium chloride staining. The increase of glutamate and glycine in the ischemic cortex of the MHTi and MHTi+r rats during ischemic and reperfusion periods was significantly less than of the NT rats (p<0.05). However, there was no statistical difference among these groups in the peak of glutamate and glycine release in the striatum. Infarct volume paralleled the release of glutamate and glyeine. The protective effect of MHTi+r reducing ischemia and reperfusion brain injury may be due to the attenuation of both glutamate and glycine release during ischemia and reperfusion.