CYTOTOXIC EFFECTS OF BLOODY CEREBROSPINAL-FLUID ON CEREBRAL ENDOTHELIAL-CELLS IN CULTURE

The release of intracellular products from lysed blood cells is believ ed to play a critical role in the etiology of vascular pathology follo wing intracerebral hemorrhage. The present studies investigated the ef fects of a mixture of blood and cerebrospinal fluid (CSF) on bovine in tracranial endothelial cells maintained in culture. The incorporation of H-3-leucine into endothelial cells was used as an index of cellular viability. Cerebrospinal fluid alone did not alter the incorporation of H-3-leucine into the cells. In contrast, CSF preincubated with bloo d for 3 days or longer prior to treatment elicited significant reducti ons in leucine incorporation. Treatment with CSF preincubated with blo od for 5 to 7 days resulted in the rapid deterioration of the culture, with large numbers of cells detaching almost immediately. Concentrati ons of hemoglobin were elevated profoundly in mixtures of blood and CS F preincubated for periods longer than 3 days. The increases in hemogl obin concentration were related temporally to increases in the cytotox ic impact of the bloody CSF. These findings suggest that factors relea sed during the breakdown of blood exert a deleterious effect on intrac ranial endothelial cells. The time course of this effect is closely re lated to the development of vasospasm in humans following subarachnoid hemorrhage. Taken together, these observations are consistent with th e hypothesis that intracellular blood products, particularly hemoglobi n, contribute to vasospasm by directly compromising endothelial functi on.