Function of Prostaglandin D Synthase in Cerebrospinal Fluid after Subarachnoid Hemorrhage / Application for the Treatment of Cerebral Vasospasm

为了验证脑脊液中的Lipocalin型前列腺素D合成酶(PGDS)可捕获或清除蛛网膜下腔出血后引起脑血管痉挛的物质，从而减少缺血性后遗症的假说，实验和临床研究结果表明：(1)SAH后第3天和第5天腰部脑脊液中的PGDS含量增加了约2倍。蛛网膜下腔出血后脑脊液中PGDS含量的一过性和延迟性升高是由于其诱导了蛛网膜下腔中的PGDS。(2)气相色谱-质谱法显示SAH患者脑脊液中与PGDS结合的物质是胆绿素。(3)人重组PGDS注射到犬蛛网膜下腔后迅速进入血液，并最终排入尿液。(4)蛛网膜下腔出血患者尿液中可见与胆绿素结合的PGDS。(5)胆绿素氧化物在体外是一种很强的血管收缩药。(6)鞘内注射PGDS有减轻SAH犬血管造影所估计的血管痉挛程度的趋势。

In order to test the hypothesis that lipocalin-type prostaglandin D synthase (PGDS) in cerebrospinal fluid (CSF) may trap or scavenge substances which cause cerevral vasospasm after subarachnoid (SAH) hemorrhage and reduce ischemic sequela, we performed experimental and clinical evaluations and obtained following results.(1) The PGDS level in lumbar CSF increased about 2-fold at day 3 and day 5. The transient and delayed increase in the PGDS level in CSF is due to its induction of PGDS in the arachnoid membrane after SAH.(2) The substance binding to PGDS in CSF of patients with SAH was shown to be biliverdin by GC mass spectroscopy.(3) Human recombinant PGDS injected into the subarachonoid space of dog was tranported to blood quickly and finall discharged into urine. PGDS injected into blood never went into CSF.(4) PGDS binding biliverdin was shown in urine of patients with SAH.(5) Biliverdin oxides was one of strong vasoconstrictors in vitro.(6) There was a tendency that intrathecal injection of PGDS might reduce the severity of vasospasm estimated by angiography using couble-injection SAH canine model.