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

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 0, 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.