DNA fragmentation in central nervous system vascular malformations

Recent studies have shown that apoptosis plays an important role in vascular remodeling. We examined central nervous system vascular malformations for the presence of DNA fragmentation which is the evidence of apoptosis. We hypothesize that vascular remodeling through apoptosis may be responsible for recurrence or hemorrhage in these lesions. We examined the specimens of central nervous system vascular malformations by in situ end labeling (ISEL) of fragmented DNA. Moreover, we examined the expression of Caspase-3 which is apoptosis-related proteins in these lesions by immunohistochemistry. DNA fragmentation was observed in all 15 arteriovenous malformation (AVM) specimens. ISEL-positive cells were mainly distributed in the endothelium, media and perivascular tissue. In cavernous hemangioma (CH), DNA fragmentation was also observed in all 5 specimens. ISEL-positive cells were distributed in the endothelium, subendothelium and intercavernous matrix. Thirteen out of 15 AVM lesions stained positive for Caspase-3. Caspase-3 immunoreactivity was mainly distributed in the endothelium, media and perivascular tissue. This distribution was similar to that of ISEL positive cells. As for CHs, all 5 lesions stained positive for Caspase-3. Caspase-3 immunoreactivity was distributed in the endothelium, subendothelium and intercavernous matrix. Our findings indicate that apoptotic cell death and vascular remodeling play a role in the development and maintenance of vascular malformations.