Using immunological studies, it was investigated whether any vasoactive substances were produced in the subarachnoid space and whether these substances effected delayed cerebral vasospasm after subarachnoid hemorrhage.
Cerebrospinal fluid (CSF) was aseptically mixed with autologous arterial whole blood or its fractions; red blood cells, serum, inactivated serum, platelet-rich lymphocytes, aggregated immunoglobulin G, or dried pepsin-treated human immunoglobulins G. Each mixture was incubated at 37°C for 7 days. Instead of CSF saline was used for controls. White sediments were observed in the mixtures of CSF plus serum and of CSF plus inactivated serum after two days of incubation. Immunoelectrophoresis showed that immunoglobulin G decreased in the supernate of these mixtures compared with the corresponding controls. Immunofluorescence microscopy of the sediments revealed marked granular deposits of immunoglobulin G and β
1C/1A globulin. These results suggested that the mixtures of CSF plus serum and CSF plus inactivated serum might contain C
1q binding immunoglobulin. C
1q solid-phase enzyme immunoassay was then performed to measure the C
1q binding immunoglobulin in the supernate and sediment of the CSF plus serum mixture. C
1q binding immunoglobulin was not demonstrated in either CSF alone or serum alone. In the CSF plus serum mixture, however, C
1q binding immunoglobulin was detected.
It was then investigated whether the sediments and supernates containing C
1q binding immunoglobulin were biologically active. Filter paper, soaked in the sediment and supernate of each mixture, was applied to the mesenteric artery of rats. Microscopic observations were made for vasoconstriction. The mesenteric artery was constricted by three mixtures only; CSF plus whole blood, CSF plus serum, and CSF plus inactivated serum. These findings suggest that C
1q binding immunoglobulin may be formed when CSF is contaminated by serum, and that this protein will activate the complement system. As a result, vasoconstrictive substances such as C
3a and C
5a (anaphylatoxin) may be produced, which constrict the cerebral artery in the subarachnoid space.
View full abstract