Prostaglandin D2 monitoring in human CSF after subarachnoid hemorrhage: the possible role of prostaglandin D2 in the genesis of cerebral vasospasm

Abstract

Experimental and clinical studies indicate that cerebral vasospasm following subarachnoid hemorrhage (SAH) may be caused by changed biochemical properties of the endothelium and vascular smooth muscle cell exposed to vasoactive substances synthetized by cerebral arteries and released in clotted blood. Many compounds have been identified in CSF from SAH patients: Thromboxanes A2 and B2, Prostaglandins F2 alpha, E2 and D2 are the major prostanoids incriminated in the causation of cerebral arterial spasm. We have monitored the CSF PGD2 concentrations with serial lumbar punctures at different intervals from the hemorrhage in 16 patients admitted for SAH: PGD2 was measured with radioimmunoassay as its 9-methoxy derivative. The lumbar CSF PGD2 concentration ranges from 0.11 to 1.53 ng/ml. In 7 cases vasospasm was angiographically demonstrated. 9 patients presented no clinical or radiological evidence of vasospasm. In 5 cases cisternal CSF samples were available at the operation by cisternal punctures. There was no correlation between CSF PGD2 concentration and clinical course. In the 7 cases with evidence of vasospasm a significant increase of CSF PGD2 corresponded to neurological deterioration. In all 9 cases without evidence of vasospasm CSF PGD2 concentration trend was in a steady-state. The cisternal CSF PGD2 concentration was higher than lumbar CSF concentration in cases with arterial spasm. This suggests the importance of the clotting phenomenon in vasospasm onset after SAH. PGD2 is one of the most important spasmogens in clotted blood. Although its role in the genesis of vasospasm onset remains to be defined, its vasospastic action, in addition to that of other analogous compounds, seems to be relevant.

Glibenclamide Inhibits the Contractile Responses of Canine Middle Cerebral Artery to Eicosanoids and Oxyhemoglobin

“…Both Toda [32] and Lang and Maron [33] suggested that a variety of cyclooxygenase inhibitors could interfere with the effects of oxyhemoglobin or whole blood, al though these agents are ineffective in clinical vasospasm in man. Cerebrospinal fluid from patients with cerebro vascular spasm apparently contains elevated levels of prostaglandins, particularly prostaglandin D2 [17] and prostaglandin F 2a [ 15].…”

“…It has been suggested that since eicosanoids may be formed in cerebral vessels as well as brain parenchyma [ 13] and can also be released from platelets and by stimulation of the brain cortex [14], these substances should be considered as factors involved in the regulation of cerebral blood flow and in the patho genesis of vasospasm. Eicosanoids, such as prostaglandin F 2a [15], prostaglandin E2 [16], prostaglandin D2 [17] and thromboxane A2 [18], were increased and prostaglandin I2 [19] was decreased during the development of vaso spasm.…”

Analysis of how the production and activity of PGD2 affects glioma cell lines.

“…In addition to this, at such concentrations PGD 2 concentrations the natural response of T lymphocytes via the DP1 receptor is to inhibit interferon gamma (IFN-y) production; IFN-y possesses anti-tumor properties (Sandig et al, 2007;Schroder et al, 2004). Considering that human cerebral spinal fluid (CSF) contains between 0.4nM to 5.3nM PGD 2 and PGD 2 has a strong affinity for DP2, an argument could be made that PGD 2 's endogenous presence in the CSF could support GBM survival (Gaetani et al, 1986). Even though our results showed that micromolar PGD 2 had no effect on cell viability, there was a very significant increase in cell count.…”