Thrombomodulin in the central nervous system

Thrombomodulin (TM), a thrombin receptor, present on the endothelial surface of blood vessels is a major anticoagulant proteoglycan. In this work the presence of TM antigen in the human brain and in the whole central nervous system of calves was investigated by immunocytochemistry using specific antibodies against human and bovine TM. When TM antigen was well preserved by immediate fixation on frozen tissues, TM was found present in the brain vessels of all human surgical specimens examined as well as in the whole vasculature of the calf central nervous system (CNS), from the medulla to the cortex. Moreover, even without immediate fixation, TM antigen was always found on the surface of the cerebrospinal fluid (CSF) cavity: on the arachnoid and on the inner aspect of the dura mater in humans and in calves. This suggests that the proteolytic enzymes responsible for the cleavage of TM from the endothelium are not present in the CSF and in the meningeal cells. The results reported here emphasize the importance of TM in the CNS as protecting, by its antithrombogenicity, a free circulation of blood and CSF in normal and even more, in pathological situations in which the permeability of the meningeal barrier increases.