Extravascular collagen in the human epileptic brain: a potential substrate for aberrant cell migration in cases of temporal lobe epilepsy.

Abstract

Several lines of evidence have demonstrated a number of cellular changes that occur within the hippocampus in patients with temporal lobe epilepsy (TLE). These include aberrant migration of granule cells and sprouting of mossy fibers, processes that have been linked to the hyperexcitability phenomenon observed in cases of TLE. In the present study the authors examined brain tissues obtained in patients undergoing temporal lobectomy surgery and in patients at autopsy (normal human control specimens), and compared the subcellular composition of regions of the hippocampus containing dispersed granule cells. Six human hippocampi were obtained in patients undergoing temporal lobectomies for intractable seizures. The patients ranged in age from 24 to 50 years. Two of the six patients had a history of head trauma and one had experienced a febrile seizure during childhood. Immediately following excision from the brain, the tissue was placed in an acrolein-paraformaldehyde fixative. The hippocampi were processed along with six human brain control specimens obtained at autopsy for light and electron microscopic evaluation. The tissues were then labeled for collagen types I through IV. Positive collagen labeling was identified, with the aid of both light and electron microscopy, in the parenchyma of all patients with TLE but not in the control tissues. The authors report the first localization of collagen outside of the vasculature and meninges in the brains of patients with TLE. Recent evidence of collagen's chemoattractant properties and its role in epileptogenesis in animal models suggests that collagen may play a role in cellular migration and seizure activity in a subset of patients. Further studies with a larger series of patients are warranted.