Spumiform capillary basement membrane swelling: a new type of microvascular degeneration in senescent hamster.

P.O. Gerrits, R. Kortekaas, H. de Weerd, A. Veenstra-Algra, P.G. Luiten, J.J. van der Want, J.G. Veening

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Brain microvasculature plays a critical role in the regulation of homeostasis of neural tissues. The present study focuses on characteristic microvascular basement membrane (bm) aberrations in the midbrain periaqueductal gray matter (PAG) and their relation to aging. The PAG can be considered a caudal extension of the limbic system and is a key structure in the regulation of a myriad of autonomic and motor control functions. In an ultrastructural study, morphologic changes in mesencephalic PAG capillaries were assessed in aged and young hamster and compared with those in caudal brainstem areas. Bm aberrations were studied in 1200 capillaries (n = 600 young hamsters; n = 600 aged hamsters). A new, never reported variant of bm degeneration was found that presented itself as foamy-like structures accumulating within the lamina densa of notably PAG capillaries. We classified these foamy structures as 'spumiform basement membrane degenerations' (sbmd) in which we could distinguish 4 stages depending on the size and intramembranous localization, ranging from split bm (stage I), intermediate stages II and III, to extensive stage IV, affecting almost the complete capillary bm outline. In the PAG of senescent animals various stages of sbmd were observed in 92 +/- 3% of all capillaries. Stage II was most prominently present (59%), followed by stage III (20%), and stage IV (13%). These bm aberrations were clearly age-dependent because in young animals, only 5% of the PAG capillaries showed characteristics of sbmd. For comparison, in the pontine reticular formation at the PAG-level, 41% of the capillaries showed a form of sbmd, but these defects were significantly less severe (stages I-II, 98%), and caudal brainstem structures displayed no sbmd at all. In addition to sbmd, diffuse endothelial changes, disrupted tight junctions, thickening of the bm, pericyte degeneration, and gliosis were observed in PAG capillaries. It is hypothesized that selective bm permeability of PAG capillaries results in a sequence of bm damage events that start with split bm, gradually changing into more and more extensive sbmd accumulations that eventually almost completely surround the capillary. Progressive sbmd in PAG capillaries might lead to a loss of blood-brain barrier function and consequently to impairment of autonomic and motor control functions exerted by the PAG.
Original languageUndefined/Unknown
Pages (from-to)1277-86
Number of pages10
JournalNeurobiology of Aging
Issue number4
Publication statusPublished - 2013

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