Shedding light on human cerebral lipofuscin: An explorative study on identification and quantification. Issue 3 (19th September 2020)

• Record Type: Journal Article
• Authors: Hakvoort, Karlijn; Otto, Louise; Haeren, Roel; Hoogland, Govert; Schijns, Olaf; Vink, Hans; Klein, Dionne; van Zandvoort, Marc; Rijkers, Kim
• Is Part Of: Journal of comparative neurology. Volume 529:Issue 3(2021)
• Page Start: 605
• Page End: 615
• Publication Date: 2020-09-19
• Subjects: biomarker -- epilepsy -- Imaris, RRID:SCR_007370 -- lipofuscin -- oxidative stress -- quantification; Comparative neurobiology -- Periodicals; Neurology -- Periodicals; 616
• DOI: 10.1002/cne.24971
• Languages: English
• ISSNs: 0021-9967

Abstract

Abstract: Increased oxidative stress has been associated with several neurodegenerative diseases such as Alzheimer's disease, but also with neurological diseases sharing pathophysiological pathways like epilepsy. Lipofuscin is a nondegradable end‐product of oxidative stress; its cerebral presence reflects the cumulative amount of oxidative stress the brain has endured. In this study, we have observed prominent autofluorescent particles in the pial arterial wall and in neocortical parenchyma of young, drug‐resistant epilepsy patients (18–28 years old) who underwent resective brain surgery ( n = 6), as well as in older control patients ( n = 3). With fluorescence spectroscopic imaging, brightfield microscopy, histochemistry and fluorescence lifetime imaging, these autofluorescent particles were identified as the age pigment lipofuscin. An evaluation of these lipofuscin particles using Imaris© software allowed robust quantification, while the 3D properties allowed visualization of the complex configuration. We elaborate on the usefulness of lipofuscin as a marker of cumulative oxidative stress in the brain. Furthermore, we speculate on the observed differences in particle size and density that we found between young patients and older controls, which could imply a role for lipofuscin in the pathophysiology of epilepsy and possibly other neurological diseases. Abstract : The authors identified and quantified the age pigment lipofuscin within pial arterial walls and neocortical parenchyma of young drug‐resistant epilepsy patients. Lipofuscin functions as a marker of cumulative oxidative stress, and could provide insight in the pathophysiology of epilepsy.