Experimental Study on the Genesis of Cerebral Vasospasm

Abstract

Experimental Study on the Genesis of Cerebral Vasospasm• The cerebral vasospasm produced by blood, fractions of blood, and blood-borne agents administered intracisternally was studied arteriographically to attain a better understanding of the genesis of vasospasm. The results indicate this phenomenon is multifarious in origin, involving a number of spasmogens. Whole blood, platelets, platelet extracts, some isolated components of platelets, plasma, thrombin, histamine, serotonin and prostaglandins Fi o , E2 and F 2a produced a significant incidence and duration of spasm. Norepinephrine and prostaglandin Ei were inactive. Spasm produced by arachidonic acid and red blood cells was of questionable significance.Compared to whole blood, thrombin usually produced spasm which was more delayed in onset while most other active substances produced a shorter-lived spasm. However, among the pure substances tested, serotonin, prostaglandin E2 and prostaglandin F 2o induced spasm in small doses which most nearly resembled that observed with whole blood.The hypothesis that the course of spasm depends upon synthesis of spasmogens by brain and blood is advanced. Prostaglandin synthesis plays a major role in this concept.

Basic and Translational Research on Proteinase-Activated Receptors: The Role of Thrombin Receptor in Cerebral Vasospasm in Subarachnoid Hemorrhage

“…In 1975, White et al demonstrated that thrombin induced contraction in the canine basilar artery (35). Later, a link between thrombin and cerebral vasospasm in SAH was suggested by both clinical studies with SAH patients and experimental studies with animal models of SAH, as mentioned above (10 -12, 36).…”

“…Clot removal, by either surgery (13) or intrathecal application of fibrinolytic agents such as urokinase or tissue plasminogen activator (16 -18), has (10,12,35), plasmin (36), fibrin degradation products (55,56) Platelet-derived substances: serotonin (57,58), thromboxane A2 (25, 59), platelet-derived growth factor (60) Prostaglandins: PGF2α (61, 62), PGE2 (63) Reactive oxygen species and related materials: lipid hydroperoxide (6) Lipid mediators: sphingosine 1-phosphate (64), arachidonic acid (65) Vasoactive substances: endothelin-1 (66,67), angiotensin II (57,58) Increased vascular responsiveness Endothelial damage and dysfunction (3) Increased contractile responsiveness of smooth muscle Increased receptor function: PAR1 (42,43), PDGFR (68) Alteration of signaling proteins: increased activity of Rho kinase (7, 8) Table 2. Current therapeutic strategies for the treatment of cerebral vasospasm…”

The Novel 5-Lipoxygenase Inhibitor ABT-761 Attenuates Cerebral Vasospasm in a Rabbit Model of Subarachnoid Hemorrhage

“…Several putative spasmogens have been shown to be active in the development of cerebral vasospasm (7,15,18,53). It has been established that an inflammatory reaction occurs after SAH (13,57).…”

“…erebral vasospasm is the most important cause of morbidity and mortality in patients surviving subarachnoid hemorrhage (SAH), as it can compromise cerebral hemodynamics and lead to the development of delayed ischemic neurological deficits (7,18,53). The mechanism of cerebral vasospasm is still unclear, but is likely to involve a complex chain of events involving inflammatory processes taking place in the arterial wall (6,7,15,18,51).…”

Effects of cervical sympathectomy on vasospasm induced by meningeal haemorrhage in rabbits

“…Penfield, in 1932, (quoted by White et al 3 ), showed sensitive aff e rent and eff e re n t motor nerves in the adventitia and in the space between the adventitia and the muscle layer of all cerebral large and small arteries, and vein walls 3 . I n n e rvation of the human carotid vessels is supplied by the sympathetic system, originating mainly f rom the superior cervical ganglion, but also fro m the inferior 4 .…”