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.

Objective To compare the effects of mild hypothermia induced in different time courses on rats subjected to 3 hours (h) of ischemia followed by 3h or 72h of reperfusion. Methods Eighty male praue-Dawley rats were divided into three mild hypothermic (MHT, 32±0.2℃) groups, including intra-ischemia (MHTi), intra-reperfusion (MHTr), and intra-ischemia/reprefusion (MHTI+r) group, and one normothermic group (NT, 37±0.2℃) as the control. Reversible focal ischemia was carried out in rats with suture model. The cortical blood flow was measured during 3h of ischemia followed by 3h of reperfusion. The permeability of brain blood barrier (BBB) was estimated after 3h of reperfusion. The infarct volume was measured at 72h after reperfusion to determine the efects of MHT. Results The acute post-ischemic hyperperfusion and delayed hypoperfusion in ischemic perifocal region and sustained hypoperfusion in ischemic core were inhibited in MHTi+r and MHTi rats (P<0.05). MHTi+r protection on post-ischemic progressive hypoperfusion in the perifocal region was more effective than that MHTi (P<0.05). The BBB diruption and the infarct volume were significantly reduced in both MHTi and MHTi+r groups (P<0.05), especially in the MHTi+r rats. Conclusions This study demonstrates that MHTi+r has more substantial protective effects on reducing ischemia/reperfusion injury than MHTi. It may inhibit post-ischemic hyperperfusion and delayed or sustained hypoperfusion in ischemic perifocal regions, and reduce brain blood barrier disruption in the cortex region.

目的：观察Df-521巴曲酶对大鼠脑出血后脑水肿对血肿周边区脑组织ICAM-1表达的影响。方法：一侧基底节注射自体血制作大鼠脑出血模型，用干温重法，测定脑组织含水量；用免疫组化法检测血肿周边水肿带ICAM-1的表达情况。结果：大鼠脑出血后，血肿侧脑组织含水量上升，同时水肿区ICAM-1的表达量增多；给予Df-521巴曲酶制剂处理后，血肿侧脑水肿减轻，脑组织ICAM-1的表达有所下降。结论：Df-521巴曲酶能下调脑出血周边组织ICAM-1的表达并减轻脑水肿的程度。

目的：观察术前诱导并诗续至术后6-8小时亚低温（MHT）使用的安全性。方法：前瞻性对比研究53例脑动脉瘤手术病人，其中MHT组24例，常温（NT）组29例。MHT于术前麻醉时诱导，并持续至术后6-8小时。观察MHT诱导时血压、心律改变，诱导后凝血功能改变，术后复温时脑血流改变，及术后肺闻感染、上消化道出血、颅内血肿发生率。结果：①MHT诱导早期，病人血压升高，心率减慢，但均在正常生理范围内。②MHT对凝血功能无影响，且不增加肺部感染、上消化道出血、颅内出血发生率。③缓慢复温对脑血流无明显影响。结论：术前诱导并诗续6-8小时的MHT治疗是安全可靠的。

目的：研究缺血期、再灌注期、缺血持续至再灌注期亚低温对脑缺血再灌注损伤的作用。方法：32只雄性SD鼠采用线段阻塞大脑上动脉的可逆性局灶脑缺血模型，缺血3小时财灌注72小时后计算各组脑梗塞灶体积。结果：再灌注后诱导亚低温的治疗作用是有限的，缺血期，尤其是缺血期持续至再灌注期亚低温明显减轻脑缺血损伤。结论：脑缺血再灌注损伤是一个缓慢进展的过程，亚低温治疗不但要考虑到低温诱导的时间，其持续时间的长短也很重要。