ヒトくも膜下出血後攣縮血管での炎症反応の役割 : iNOS,NF-kappaB,IKKの発現について : 脳血管障害の最先端  [in Japanese] Role of Inflammation in Cerebral Vasospasm after Subarachnoid Hemorrhage: Expression of iNOS, NF-kappaB, IKK in the Major Cerebral Arteries and CSF Samples in Humans  [in Japanese]

くも膜下出血後の脳血管攣縮に対し, 多くの治療法が試みられており, いくつかの成果がすでに発表されているが, いまだに満足の得られる治療法が確立されたとはいいがたい. その理由は, 脳血管攣縮機序解明の研究が動物実験主体で進んでおり, 倫理面などの問題からヒトにおける研究が, ここ20年盛んではなかったことに起因すると思われる. 今回, われわれは, ヒト剖検例で脳血管攣縮をきたした血管を用いて, 炎症反応関連因子における組織学的, 分子生物学的検討を加えることのできた症例を経験したので, 他のくも膜下出血患者の脳脊髄液のデータも併せて, 炎症関連因子のヒト脳血管攣縮への関与について検討した. 症例と方法 症例は74歳, 男性, 突然の頭痛にて発症し, 即日当科に緊急搬入された. 来院時, 意識レベルはJapan coma scaleで200点, 瞳孔不同を認めた. Hunt & Kosnik gradeは4, 頭部CTではFisher group3のくも膜下出血(SAH)を認めた. 即日脳血管撮影を施行し, 前交通動脈瘤破裂によるSAHと診断するとともに, grade4であることから, 同時に血管内手術によるコイル塞栓術を行った.

We had an autopsy case who had suffered from severe subarachnoid hemorrhage (SAH). The case was a 74 year-old man who was in Fisher Group 3 and Hunt &Kosnik Grade 3 on admission. He was treated by intraarterial coil embolization to the anterior communicating artery aneurysm on Day O, but the aneurysm reruptured on Day 8. Angiograms on Day 8 showed mild to moderate vasospasm in the right, anterior and middle cerebral arteries. Although recoiling to the resting neck was performed immediately, the patient died on Day 11. We were able to harvest the major cerebral arteries just 2 hours after death. RNA was extracted from each artery and then reverse transcription-polymerase chain reaction (RT-PCR) was carried out using human inducible nitric oxide synthase (iNOS) primers. Histological and immunocytochemical examination was done for iNOS, NF-kappaB, and I-kappaB kinase (IKK). Enzyme-Linked Immunosorbent Assay (ELISA) was performed using the cerebrospinal fluid of SAH patients who suffered from vasospasm for detecting iNOS protein. iNOS messenger RNA was up-regulated in the vasospastic arteries compared to the non-spastic one. Hematoxylin-eosin staining revealed that there were many white blood cells in both sides of the vascular wall. iNOS has been detected in some patients who suffered from SAH and was remarkably higher than that in patients showing no vasospasm but has not, been detected in normal cerebrospinal fluid. On Day 5, iNOS protein in the CSF was highest during the course after SAH. These results suggest that inflammation, especially, vascular injury by iNOS, may be important to understand the pathogenesis of cerebral vasospasm.