CEREBROVASCULAR CHANGES FOLLOWING ADMINISTRATION OF GAMMA-GLOBULINS AGAINST SUBSTANCE-P OR CALCITONIN-GENE-RELATED PEPTIDE IN MONKEY WITH SUBARACHNOID HEMORRHAGE

Cerebrovascular changes after intrathecal (ith) administration of gamm aglobulins against substance P (SP) or calcitonin gene-related peptide (CGRP) were investigated before and following a simulated subarachnoi d haemorrhage (SAH) in the squirrel monkey. The SAH was produced by in jection of homologous blood into the interpeduncular fossa and the cis terna magna. The gammaglobulins were given both prior to the blood inj ections and daily in 5 days post-SAH. The effect of the gammaglobulins was examined by angiography pre-SAH and at 10 min and at 6 days post- SAH, i.e. the time points for maximal acute and late spasm in the pres ent model. Cerebral blood flow (CBF) was measured under general anesth esia at day 6 post-SAH with an autoradiographic technique. Five of nin e animals treated with CGRP antigammaglobulin died from respiratory fa ilure. Four animals received SP antiganimaglobulin and two control ani mals received normal globulin. SP antigammaglobulin per se had no effe ct on baseline arterial diameter, while CGRP antigammaglobulin signifi cantly reduced the diameter of the arteries. SP antigammaglobulin prev ented the occurrence of acute spasm and significantly reduced the degr ee of late spasm. Moreover, the reduction in CBF noted in the control SAH animals was significantly reduced. In contrast, CGRP antigammaglob ulin treatment had no effect on the degree of spasm and did not cause any change in CBF as compared to controls. The finding that CGRP but n ot SP antigammaglobulin significantly reduces the arterial diameter in conjunction with our previous demonstration that a post-, but not pre ganglionic trigeminal lesion reduces the baseline arterial diameter, i ndicates that CGRP could be the transmitter involved in a peripheral a xon reflex. The function of SP might be as a neurotransmitter conveyin g information to the brainstem. The transmitter role is supported by t he effect of SP antigammaglobulin impairing SP containing neurons and, in that way, mimicking a bilateral trigeminal rhizotomy.