凝血酶与神经细胞凋亡的实验观察

目的 观察凝血酶与脑细胞凋亡的关系及使用凝血酶抑制剂(如水蛭素)及钙离子拮抗剂(尼莫地平),能否减轻凝血酶对脑细胞的毒性损伤、存在治疗的有效时间。方法 分别以不同剂量的凝血酶注入SD大鼠尾状核,建立SD大鼠模型,在普通光镜(采用HE染色,TUNEL法)及电镜下观察脑细胞凋亡。SD大鼠随机分为6组。1组:生理盐水组;2组:小剂量凝血酶组;3组:大剂量凝血酶组;4组:小剂量凝血酶与小剂量水蛭素同时注入组;5组:大剂量凝血酶与大剂量水蛭素同时注入组;6组:尼莫地平组。每组每时相(4h、24h、48h、3d、7d)各5只SD大鼠)。结果 建立动物模型后各时相点大剂量凝血酶组凋亡细胞数与其余各组比PO.05。结论 大剂量凝血酶可导致神经细胞凋亡.早期(4h)即出现,其高峰时间在24～48h,可持续1周以上,水蛭素能特异性抑制凝血酶的作用,而钙离子拮抗剂可减少或延迟凋亡细胞的出现。脑出血后血肿释放的凝血酶是早期诱导细胞凋亡的重要因素,如能尽早抗凝血酶治疗或抗凋亡治疗(本实验提示最好在48h内),将为脑出血治疗提供新的途径。     

大鼠脑出血后血肿周围凝血酶与脑细胞凋亡和脑水肿的关系

目的 研究大鼠脑出血后血肿周围脑组织中凝血酶的变化及其与脑细胞凋亡和脑水肿的关系.方法 105只成年雄性SD大鼠随机均分为脑出血组、生理盐水组和正常对照组.每组再随机均分为7个时相,分别为6 h、12 h、24 h、48 h、3 d、5 d、7 d;用立体定向脑内注射法制备脑出血模型;用ELISA法检测脑组织中凝血酶-抗凝血酶复合物的含量;用流式细胞仪检测脑细胞的凋亡率;用干-湿重法检测脑组织的含水量;用透射电镜观察脑组织的形态学变化.结果 制备动物模型后,脑出血组各时相血肿周围脑组织中凝血酶含量、脑细胞凋亡率、脑组织含水量均明显高于生理盐水组和正常对照组;血肿周围脑组织中凝血酶-抗凝血酶复合物的含量与脑细胞凋亡率和脑组织含水量之间均呈正相关;电镜下,在脑出血组各时相脑组织切片中均可见大量的脑细胞凋亡和毛细血管周围大片组织间隙水肿,以及神经纤维脱髓鞘改变.结论 脑出血后,血肿周围脑组织中凝血酶含量明显升高,可导致脑细胞凋亡和脑水肿,凝血酶的含量与脑细胞凋亡率和脑组织含水量呈正相关;尽早清除血肿有望改善凝血酶引起的继发性脑损伤.     

大鼠脑出血后血肿周围凝血酶与脑细胞凋亡和脑水肿的关系

目的 研究大鼠脑出血后血肿周围脑组织中凝血酶的变化及其与脑细胞凋亡和脑水肿的关系.方法 105只成年雄性SD大鼠随机均分为脑出血组、生理盐水组和正常对照组.每组再随机均分为7个时相,分别为6 h、12 h、24 h、48 h、3 d、5 d、7 d;用立体定向脑内注射法制备脑出血模型;用ELISA法检测脑组织中凝血酶-抗凝血酶复合物的含量;用流式细胞仪检测脑细胞的凋亡率;用干-湿重法检测脑组织的含水量;用透射电镜观察脑组织的形态学变化.结果 制备动物模型后,脑出血组各时相血肿周围脑组织中凝血酶含量、脑细胞凋亡率、脑组织含水量均明显高于生理盐水组和正常对照组;血肿周围脑组织中凝血酶-抗凝血酶复合物的含量与脑细胞凋亡率和脑组织含水量之间均呈正相关;电镜下,在脑出血组各时相脑组织切片中均可见大量的脑细胞凋亡和毛细血管周围大片组织间隙水肿,以及神经纤维脱髓鞘改变.结论 脑出血后,血肿周围脑组织中凝血酶含量明显升高,可导致脑细胞凋亡和脑水肿,凝血酶的含量与脑细胞凋亡率和脑组织含水量呈正相关;尽早清除血肿有望改善凝血酶引起的继发性脑损伤.     

水蛭素和重组链激酶联合应用于脑出血血肿腔中的实验研究

目的研究水蛭素和重组链激酶联合应用于脑内出血(ICH)血肿腔中对血肿周围脑组织的影响.方法 72只SD雄性大鼠制成ICH模型,随机分为对照组、重组链激酶组、水蛭素 重组链激酶组(联合组),各组分别在ICH后8 h、16 h、24 h、48 h向血肿腔中注入生理盐水、重组链激酶、或重组链激酶加水蛭素.ICH后72 h处死大鼠,观察脑组织中的含水量、Na 、K 以及血脑屏障通透性的变化.结果在ICH后8 h、16 h、24 h、48 h应用重组链激酶,可引起脑组织含水量增加以及Na 、K 的变化(P<0.05),在ICH后8 h重组链激酶组,脑组织中伊文思蓝(Evans blue,EB)含量明显升高(P<0.05).联合组与重组链激酶组比较脑组织的含水量在8 h、16 h、24 h、48 h明显降低(P<0.05),脑组织中EB含量在8 h、16 h、24 h、48 h也明显降低(P<0.05).结论 ICH血肿腔内单独应用重组链激酶可加重ICH血肿周围脑组织的损伤,联合应用水蛭素不但可防治重组链激酶溶化血块时对脑组织的损伤,而且还可降低血肿本身所释放的毒性物质所引起的脑水肿及血脑屏障的破坏.     

脑出血大鼠脑组织IGF-1的表达及其对细胞凋亡的影响

目的研究胰岛素样生长因子-1（IGF-1）在实验性大鼠脑出血（ICH）后脑组织中的表达及其对细胞凋亡的影响。方法应用立体定向技术，将自体未抗凝血注入大鼠基底节区以制备ICH模型；将动物分为正常对照组、ICH组及干预组，分别在不同时间断头取脑以制作标本，连续切片分别作IGF-1免疫组化染色及TUNEL染色。结果ICH后2h血肿周围脑组织表达IGF-1，24h达表达高峰，7d时恢复正常；TUNEL染色阳性细胞于ICH后8h开始出现，3d时达高峰，7d时仍有表达；给予外源性IGF-1后，凋亡细胞显著减少，与同时点ICH组相比差别有显著性。结论ICH后IGF-1可抑制细胞凋亡的发生，从而减轻ICH后继发性脑损伤。     

大鼠脑出血后血肿周围凝血酶与脑细胞凋亡和脑水肿的关系

目的 研究大鼠脑出血后血肿周围脑组织中凝血酶的变化及其与脑细胞凋亡和脑水肿的关系.方法 105只成年雄性SD大鼠随机均分为脑出血组、生理盐水组和正常对照组.每组再随机均分为7个时相,分别为6 h、12 h、24 h、48 h、3 d、5 d、7 d;用立体定向脑内注射法制备脑出血模型;用ELISA法检测脑组织中凝血酶-抗凝血酶复合物的含量;用流式细胞仪检测脑细胞的凋亡率;用干-湿重法检测脑组织的含水量;用透射电镜观察脑组织的形态学变化.结果 制备动物模型后,脑出血组各时相血肿周围脑组织中凝血酶含量、脑细胞凋亡率、脑组织含水量均明显高于生理盐水组和正常对照组;血肿周围脑组织中凝血酶-抗凝血酶复合物的含量与脑细胞凋亡率和脑组织含水量之间均呈正相关;电镜下,在脑出血组各时相脑组织切片中均可见大量的脑细胞凋亡和毛细血管周围大片组织间隙水肿,以及神经纤维脱髓鞘改变.结论 脑出血后,血肿周围脑组织中凝血酶含量明显升高,可导致脑细胞凋亡和脑水肿,凝血酶的含量与脑细胞凋亡率和脑组织含水量呈正相关;尽早清除血肿有望改善凝血酶引起的继发性脑损伤.     

经腹腔应用阿加曲班对脑出血后凝血酶神经毒性的抑制作用

目的:探讨经腹腔应用阿加曲班治疗脑出血（ICH）后凝血酶神经毒性损伤的可能性。方法:①研究阿加曲班对ICH及凝血酶注入后脑水肿、细胞损伤的影响。Wistar大鼠60只,随机分为假手术对照组（只进针不注血）;ICH组（50μL自体尾血注入右尾状核）;ICH+阿加曲班干预组(50μL自体尾血注入大鼠右侧尾状核,分别于术后3和12h经腹腔给予阿加曲班0.9mg·kg^-1,总量0.6mL);凝血酶组(10U·2μL^-1凝血酶注入大鼠右侧尾状核);凝血酶+阿加曲班干预组(10U·2μL^-1凝血酶注入大鼠右侧尾状核,分别于术后3和12h经腹腔给予阿加曲班0.9mg·kg^-1,总量为0.6mL)。各组均n=12,术后24h处死各组大鼠,每组中6只用于检测脑组织水含量,6只检测caspase-3免疫反应细胞及TUNEL阳性细胞数。②经腹腔注射阿加曲班对血肿容积的影响:建立胶原酶ICH大鼠模型组:注入Ⅰ型胶原酶+肝素;阿加曲班组:胶原酶ICH模型成功后3及12h分别经腹腔注入阿加曲班溶液0.9mg·kg^-1,每次注入液体量为0.6mL,测定两组大鼠脑组织血肿血红蛋白的含量(测定血红蛋白A₅₅₀值)以评价阿加曲班对血肿容量的影响。结果:自体血ICH及凝血酶模型大鼠在阿加曲班干预后,ICH组及凝血酶组的TUNEL阳性细胞数、caspase-3阳性细胞数明显下降（P<0.01或P<0.05）,脑组织水肿含量百分比明显降低（P<0.05）。胶原酶ICH血红蛋白A值为（0.45±0.12）,阿加曲班干预组为（0.46±0.09）,差异无统计学意义（P>0.05）。结论:ICH后3～12h经腹腔注入阿加曲班可减轻ICH后的脑水肿及细胞凋亡性损伤,且没有血肿增大的不良反应。     

脑出血后脑组织内凝血酶受体1(PAR1)的表达及其病理意义

目的　探讨脑出血后脑组织内凝血酶受体 1(PAR1)的表达规律及其意义。方法　成年大鼠分为 3组 ,分别向大脑基底节区注入全血、全血加水蛭素、或生理盐水。于注射后 6 h、2 4 h、72 h和 7d,取脑组织 ,检测脑内PAR1表达 (免疫组织化学法 )。同时 ,观察神经细胞的凋亡情况 (Tunel法 )和脑组织水含量 (干燥法 )。结果　与生理盐水对照组比较 ,脑出血后血肿周围脑组织内 PAR1免疫阳性细胞数明显升高 (P<0 .0 5 )。同时 ,脑组织内凋亡细胞数和脑组织水含量也明显增加。时效学研究显示 ,PAR1表达上调开始于脑出血后 6 h,72 h达高峰 ,7d后下降。加用凝血酶抑制剂 -水蛭素者 ,出血周围组织内 PAR1表达明显抑制 ,同时脑组织水肿和神经凋亡显著减轻。结论　脑出血后脑组织 PAR1表达增加。 PAR1高表达可能介导了脑出血后神经损伤的过程。     

亚低温抑制大鼠弥漫性脑损伤后细胞凋亡的研究

目的探讨大鼠不同程度弥漫性脑损伤后脑组织的凋亡变化过程及亚低温治疗对脑细胞凋亡的抑制作用.方法采用大鼠Marmarou颅脑创伤装置制作弥漫性脑损伤模型,然后将128只Wistar大鼠分为未损伤组(对照组)、重度损伤组、轻度损伤组和亚低温治疗组.通过电子显微镜、组织切片原位末端标记DNA片段(TUNEL染色)、琼脂糖凝胶电泳(DNA Ladder法)等方法,观察和比较不同程度脑损伤后,大鼠脑皮层及海马区凋亡细胞的形态、特点和数量.结果(1)损伤后24～48 h,皮层及海马区可见大量细胞皱缩、核碎裂、核不规则等细胞凋亡现象,48 h较24 h更为严重;亚低温治疗后24～48 h,电子显微镜观察皮层及海马区未见细胞皱缩、核碎裂等细胞凋亡现象.(2)TUNEL染色结果显示,随着损伤程度的加重凋亡明显加重,损伤后48 h达高峰,然后逐渐下降.轻度损伤组细胞凋亡主要限于海马CA2和CA3区;重度脑损伤组细胞凋亡涉及整个海马结构,同时还广泛累及额顶区皮质.损伤后第24、48、72 h,皮层及海马区的凋亡细胞数量较同期未治疗组明显减少.(3)重度损伤后48 h,海马和皮层区细胞琼脂糖电泳可见典型的DNA梯状带,其他时间未见梯状带.亚低温治疗组、轻度脑损伤组及未损伤组亦未见梯状带.结论轻度弥漫性脑损伤后,脑细胞凋亡多发生于海马CA2和CA3区;重度脑损伤后皮层及海马区细胞可发生广泛凋亡.细胞凋亡随着损伤程度的加重而加重,高峰位于伤后第2 d.亚低温治疗可有效地抑制大鼠弥漫性脑损伤后的细胞凋亡.     

脑出血后血肿腔内应用纤溶酶原激活剂对血肿周围脑组织的影响

目的研究脑出血后血肿腔内应用重组组织型纤溶酶原激活剂(r-TAP)对血肿周围脑组织的影响。方法72只SD雄性大鼠制成ICH模型,随机分为对照组、r-TPA组、水蛭素组,各组分别在ICH后4 h、8 h、12 h、16 h于血肿腔中注入生理盐水、r-TPA、或r-TPA加水蛭素。ICH后24 h处死大鼠,观察脑组织中的含水量、Na~ 、K~ 以及血脑屏障通透性的变化。结果在ICH后4 h、8 h、12 h、16 h应用r-TPA,可引起脑组织含水量显著增加(P＜0．05),Na 、K~ 的明显变化(P＜0．05)以及脑组织中伊文氏蓝含量明显升高(P＜0．05)。如同时加用水蛭素则可明显减少上述变化(P＜0．05)。结论ICH后血肿腔中应用纤溶酶原激活剂可加重ICH后血肿周围脑组织的损伤,联合应用水蛭素不但可防治纤溶酶原激活剂溶化血块时对脑组织的损伤,而且还可降低血肿本身所释放的毒性物质所引起的脑水肿及血脑屏障的破坏。     

脑出血后脑水肿经时变化机制的探讨

目的 研究脑出血(mtracerebral hemorrhage，ICH)后血肿周围脑水肿与血脑屏障(blood-brain barrier，BBB)随时间变化的机制，从而为预防脑水肿提供依据。方法90只大耳白兔随机分为3组。1组：在立体定向仪下将300μl生理盐水注入兔左侧基底节；2组：注入200μl自身动脉血与100μl生理盐水；3组：注入200μl自身动脉血与100μl水蛭素。每组每时相(6h、12h、24h、48h、72h)各6只兔。脑组织含水量采用干湿重法测量，血脑屏障的通透性测定采用伊文思兰法。结果动脉血组及水蛭素干预组血肿周围脑组织含水量均在48h达到高峰．此后逐步降低。动脉血组伊文思兰(EB)于24h到达高峰，水蛭素干预组伊文思兰(EB)于48h达高峰。结论脑出血后脑水肿是多种因素综合作用的结果。早期可能和血块凝缩、流体静力压有关；至中期时凝血酶是主导因素；后期则主要由于红细胞裂解物的损害。     

弥漫性脑损伤神经细胞凋亡及神经生长因子干预的实验研究

目的探讨弥漫性脑损伤后神经细胞凋亡及脑组织水肿情况及神经生长因子对此的干预作用。方法采用Marmarou脑损伤模型。将Spraque—Dawley鼠40只随机分成脑损伤组,神经生长因子治疗组和生理盐水对照组。治疗组分别于致伤后10min和60rain腹腔内注射神经生长因子（30mg／kg）,对照组注射等量生理盐水,于伤后24h、48h、72h和96h断头取脑,采用原位末端标记法检测凋亡细胞,对比各时段脑水肿和神经细胞的凋亡情况。结果神经细胞从伤后24h出现细胞凋亡,48～72h达高峰,治疗组与损伤组在24h,48h,72h和96h时脑组织含水量有显著性差异（P〈0．05）,对照组与损伤组含水量无显著性差异（P〉0．05）。结论神经生长因子对脑损伤性脑水肿及神经细胞凋亡有治疗作用。     

Changes in brain polyamine levels following head injury.

The changes in polyamines levels in the brain after closed head injury were studied in rats. At 1 and 15 min, 24 and 48 h after closed head injury cortical tissue from the site of injury, from the contralateral region, and from remote areas were taken. The levels of the diamine putrescine and the polyamines spermine and spermidine were assayed by thin layer liquid chromatography of their dansyl derivatives. Head injury induced a significant increase in putrescine at 48 h at the site of injury and in the frontal lobe of the injured hemisphere, respectively. In the contralateral hemisphere only minor changes in putrescine were found. Spermine and spermidine showed minor changes at that time course. We have previously shown that at 24-48 h after injury, severe edema is found at the site injury. In order to study the role of putrescine in edema formation in this model we treated the traumatized rats with alpha-difluoromethyl-ornithine (DFMO), an inhibitor of ornithine-decarboxylase, the rate limiting enzyme in putrescine biosynthesis. This drug did not affect the level of edema 4 or 48 h after injury although it abolished the increase in putrescine. The effect of DFMO on blood-brain barrier function was studied, using Evans blue extravasation, at the early post-traumatic period (15 min-4 h), where a massive amount of dye is taken up by traumatized brain. No changes in the amount of dye extracted was found after DFMO treatment. On the other hand, DFMO had a beneficial effect on the neurological outcome, as evaluated by a set of clinical criteria.(ABSTRACT TRUNCATED AT 250 WORDS)     

微创清除血肿和重组水蛭素治疗脑出血后脑水肿的实验研究

目的探讨微创清除血肿和局部应用重组水蛭素对大鼠出血性脑水肿的治疗作用。方法成年雄性SD大鼠随机分为生理盐水组、脑出血组、微创组、水蛭素组、微创 水蛭素组,治疗时间点统一为出血后3h,以自体血注入大鼠尾状核方法建立脑出血模型,应用干-湿重法观察脑水肿变化,HE染色观察水肿细胞形态。每组每时相点(12h、24h、48h、72h、7d)6只大鼠。结果脑出血组和各治疗组脑含水量与生理盐水组在12h、24h、48h比,P<0.05;7d时各组间无明显差异(P>0.05);微创组与脑出血组组间比较,P>0.05;微创 水蛭素组与脑出血组组间比较,P<0.05。结论脑出血后早期(<3h)分别予以微创清除血肿、局部应用水蛭素及二者联合治疗可显著改善脑水肿,尤其微创与凝血酶抑制剂联合应用为脑出血治疗开辟新途径。     

Attenuation of thrombin-induced brain edema by cerebral thrombin preconditioning.

BACKGROUND AND PURPOSE: Edema formation after intracerebral hemorrhage has been linked to thrombin toxicity induced by the clot. However, thrombin at low concentrations actually protects neurons and astrocytes in culture from hypoglycemic and ischemic cell death. It is also known that a brief episode of brain ischemia increases neuronal tolerance to a subsequent severe ischemic episode. The objective of this study was to investigate whether pretreatment of the brain with low-dose thrombin induces tolerance to a subsequent large dose of thrombin injected into brain parenchyma. METHODS: The rat brain was preconditioned with 1 U thrombin by direct infusion into the right caudate nucleus. After thrombin pretreatment, the effects of a large dose (5 U) of thrombin on brain edema formation were studied at different intervals. We examined whether heat-shock protein (HSP) 27, HSP32, and HSP70 were induced by Western blot analysis, immunocytochemistry, and immunofluorescent double staining. RESULTS: Thrombin pretreatment significantly attenuated the brain edema that normally follows the infusion of a large dose of thrombin (79.2+/-0.4 versus 84.0+/-0.3; P<0.01). This effect was abolished by the thrombin inhibitor hirudin. Time course studies showed that the maximal effect of thrombin preconditioning (TPC) on brain edema formation was 7 days after pretreatment. This time course corresponded to marked upregulation of HSP27 in the ipsilateral brain. TPC also induced HSP32, but this effect occurred earlier than the effect on edema formation. TPC had no effect on HSP70. Immunocytochemistry and immunofluorescent double labeling showed that HSP27 and HSP32 were expressed in astrocytes after TPC. CONCLUSIONS: OFF phenomenon of thrombin-induced tolerance of the brain to edema formation may be related to HSP27 induction.     

Induction of apoptosis by thrombin in the cultured neurons of dorsal motor nucleus of the vagus

Background A previous study demonstrated the presence of protease‐activated receptor (PAR) 1 and 2 in the dorsal motor nucleus of vagus (DMV). The aim of this study is to characterize the effect of thrombin on the apoptosis of DMV neurons. Methods The dorsal motor nucleus of vagus neurons were isolated from neonatal rat brainstems using micro‐dissection and enzymatic digestion and cultured. Apoptosis of DMV neurons were examined in cultured neurons. Apoptotic neuron was examined by TUNEL and ELISA. Data were analyzed using anova and Student’s t‐test. Key Results Exposure of cultured DMV neurons to thrombin (0.1 to 10 U mL^?1) for 24 h significantly increased apoptosis. Pretreatment of DMV neurons with hirudin attenuated the apoptotic effect of thrombin. Similar induction of apoptosis was observed for the PAR1 receptor agonist SFLLR, but not for the PAR3 agonist TFRGAP, nor for the PAR4 agonist YAPGKF. Protease‐activated receptors 1 receptor antagonist Mpr(Cha) abolished the apoptotic effect of thrombin, while YPGKF, a specific antagonist for PAR4, demonstrated no effect. After administration of thrombin, phosphorylation of JNK and P38 occurred as early as 15 min, and remained elevated for up to 45 min. Pretreatment of DMV neurons with SP600125, a specific inhibitor for JNK, or SB203580, a specific inhibitor for P38, significantly inhibited apoptosis induced by thrombin. Conclusions & Inferences Thrombin induces apoptosis in DMV neurons through a mechanism involving the JNK and P38 signaling pathways.     

高血压脑出血早期血肿周围脑组织细胞凋亡与凝血酶表达相关性的研究

目的探讨高血压脑出血(HICH)早期血肿周围脑组织细胞凋亡与凝血酶表达的关系。方法取36例高血压脑出血患者血肿周围脑组织作为实验组,按发病至手术的时间分为5组:<6h(7例)、6~12h(11例)、12~24h(8例)、24~48h(6例)、48~72h(4例)。另将侧脑室肿瘤患者经皮层入路取得的正常脑组织作为对照组。采用脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)检测神经细胞凋亡率,免疫组织化学方法检测凝血酶表达。结果对照组脑组织基本无TUNEL阳性细胞(0.32±0.037);<6h组有轻微表达(7.19±2.53,P<0.05),发病6h后逐渐增高(15.11±3.69,P<0.01),12~24h增高显著(28.26±7.83,P<0.01),并于24~48h达高峰(53.79±6.35,P<0.01),48~72h组有所回落,但仍维持较高水平(38.23±3.29,P<0.01)。凝血酶表达变化与此一致。相关分析显示:细胞凋亡与凝血酶表达呈显著正相关(r=0.7451,P<0.05或P<0.01)。结论H ICH患者血肿周围脑组织中存在细胞凋亡,凝血酶表达是细胞凋亡过程中的一个关键事件     

非开颅蛛网膜下腔出血大鼠脑血流量和水、电解质含量研究

利用非开颅大鼠模型观察蛛网膜下腔出血（ＳＡＨ）后２４ｈ内脑血流量和水电解质含量的动态变化和尼莫地平对其影响。结果发现ＳＡＨ后脑血迅速降低，１ｈ了低值，２４ｈ内持于低水平状态。ＳＡＨ后１ｈ开始脑组织Ｃａ＾２＋答聚，６ｈ后出现脑水肿。尼莫地平对上述指标均有改善作用。提示脑血管痉挛及微循环异常所致脑血流减少在ＳＡＨ继发性的损害中起重要作用，尼莫地平可减轻上述病理改变。     

Brain edema after intracerebral hemorrhage in rats: the role of inflammation

BACKGROUND: Intracerebral hemorrhage (ICH) results in secondary brain edema and injury that may lead to death and disability. ICH also causes inflammation. It is unclear whether inflammation contributes to brain edema and neuron injury or functions in repairing the brain tissue. AIMS: To understand the effect of inflammation in ICH, we have carried out an investigation on the various aspects and the dynamic changes of inflammation. SETTINGS AND DESIGN: An ICH model was generated by injecting 50 microl autologous tail artery blood stereotactically into the right caudate nucleus of 30 rats, which were randomly divided into five ICH groups. Similarly, five Sham control groups were generated by inserting the needle to the right caudate nucleus of rats. MATERIALS AND METHODS: Rat behavior was evaluated over the time course (6 h, 24 h, 48 h, 72 h and 7 d) in each group. The rats were then killed by administering an overdose of pentobarbital. Following the euthanasia, the brain water content, neuronal loss, glia proliferation, inflammatory infiltration and brain morphology of the rats were measured. Additionally, the expression of TNF-alpha, IL-6, ICAM-1, VEGF, NF-kappaB, C3 and CR2 was analyzed by immunohistochemistry. STATISTICAL ANALYSIS: The data were analyzed by student's t test. RESULTS: Rat brain water content increased progressively over the time course and reached its peak at 48 h followed ICH. The maximum of inflammatory infiltrate (especially neutrophils) and immunopositive cells of TNF-alpha, IL-6 and NF-kappaB, were at 48 h. The expression of C3 and CR2 reached their peaks at 48-72 h, while the expression ICAM-1 and VEGF were at maximum at 72 h followed ICH. CONCLUSIONS: The results suggested that the inflammatory cytokines, complement system and VEGF may have a function in the development of the brain edema and neuron injury followed ICH.