Pericyte Degeneration and Thickening of Basement Membranes of Cerebral Microvessels in Complex Partial Seizures: Electron Microscopic Study of Surgically Removed Tissue

Abstract

Abstract Complex partial seizures are associated with alterations in regional cerebral blood flow in abnormally spiking foci, as shown by positron emission tomography and single photon emission computed tomography, with an increase in flow ictally and a decrease interictally. Alterations of vasoregulation during ictal periods have also been described in animal seizure models. An electron microscopic study on human brain tissue from seven patients undergoing resections for the treatment of intractable complex partial seizures was performed to examine ultrastructural changes of the microvasculature and their locations within the microvessel wall. Biopsies were obtained intraoperatively from temporal lobe regions with electrocorticographically detected abnormal spiking and from regions without abnormality on electrocorticograms (control samples) removed as part of the therapeutic resection. A total of 539 microvessels from three regions were evaluated: spiking mesial temporal lobe, spiking lateral temporal cortex, and nonspiking (control) cortex. Evidence of pericyte degeneration (aggregates of cellular debris within the basement membrane) was noted in the majority of spiking area microvessels (76.7% in spiking mesial temporal cortex; 69.8% in spiking lateral temporal cortex) as compared with 37.8% of control microvessels (P< 0.0005). Morphometric studies revealed a significant increase in total wall thickness, pericyte-basement membrane unit thickness, pericyte cytoplasmic density, basement membrane density, and basement membrane thickness in microvessels from spiking (mesial and lateral temporal cortex), as compared to control areas (P< 0.01). No statistically significant difference was noted in pericyte coverage or pericyte or endothelial mitochondrial densities between microvessels in spiking and control regions. This study shows degeneration of pericytes, cells thought to play an essential role in microvascular hemodynamics, and thickening of microvessel walls in abnormally spiking brain regions in patients with intractable complex partial seizures. The pericyte degeneration and basement membrane thickening in abnormally spiking areas may explain alterations in vasoregulation, by a decrease in the microvascular compliance and in cross-capillary diffusion.