Thrombomodulin and the brain

Abstract

In this issue of Neurology ®, Giwa et al.1 report robust expression of thrombomodulin (TM) in small vessel disease, i.e., in small brain arteries or arterioles that exhibit the typical hyalinized thickening characteristic of chronic hypertensive changes. Using immunohistochemistry of postmortem brain tissue, the authors demonstrate extensive presence of TM in these small arterial vessels, with substantial association between extent of extent of vessel sclerosis and TM expression. Not only was small vessel TM expression significantly less in age-matched controls, but younger subjects with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy also exhibited increased TM expression in small caliber arterial vessels. Enhanced expression of TM thus appears to be characteristic of cerebral small vessel disease, and the authors suggest that the TM in this setting may be both compensatory and protective. It would be an understatement to say that TM is not commonly discussed within neurologic circles. Within the field of vascular biology, however, TM remains an intense focus of attention, with a recent review article even referring to this molecule as the “protectorate God of the vasculature.”2 TM is an integral membrane protein routinely found in vascular endothelium of …