Microvascular changes in estrogen-α sensitive brainstem structures of aging female hamsters

Gerrits, Peter O.; Weerd, Henk de; Want, J.J.L. van der; Kortekaas, Rudie; Luiten, P.G.M.; Veening, Jan G.

doi:10.1016/j.neures.2010.04.010

Cited by 10 publications

(14 citation statements)

References 28 publications

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“…In fact, cerebral microvessels from a small sample of pre and post-menopausal women also confirmed this reproductive age-related loss of junctional localization (Bake et al 2009). Disrupted tight junctions are also seen in aging female hamsters (Gerrits et al 2010), although this is uncoupled from reproductive senescence.…”

Section: Endothelial Cellsmentioning

confidence: 99%

“…In an in vitro BBB model, astrocytes and pericytes responded to hypoxia causing endothelial cell death but pericytes were able to maintain the barrier function better than astrocytes under prolonged oxygen deprivation (Al Ahmad et al 2011). In reproductive senescent female hamsters, vascular changes in endothelial cells and tight junctions were paralleled by pericyte degeneration and thickening of the basement membrane (Gerrits et al 2010). Age and hormone related changes in this cell type thus represent another important but understudied area that will impact stroke outcomes.…”

Section: Pericytesmentioning

confidence: 99%

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Age-related changes in brain support cells: Implications for stroke severity

Sohrabji

Bake

Lewis

2013

Neurochemistry International

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Stroke is one of the leading causes of adult disability and the fourth leading cause of mortality in the US. Stroke disproportionately occurs among the elderly, where the disease is more likely to be fatal or lead to long-term supportive care. Animal models, where the ischemic insult can be controlled more precisely, also confirm that aged animals sustain more severe strokes as compared to young animals. Furthermore, the neuroprotection usually seen in younger females when compared to young males is not observed in older females. The preclinical literature thus provides a valuable resource for understanding why the aging brain is more susceptible to severe infarction. In this review, we discuss the hypothesis that stroke severity in the aging brain may be associated with reduced functional capacity of critical support cells. Specifically, we focus on astrocytes, that are critical for detoxification of the brain microenvironment and endothelial cells, which play a crucial role in maintaining the blood brain barrier. In view of the sex difference in stroke severity, this review also discusses studies of middle-aged acyclic females as well as the effects of the estrogen on astrocytes and endothelial cells

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Section: Endothelial Cellsmentioning

confidence: 99%

Section: Pericytesmentioning

confidence: 99%

Age-related changes in brain support cells: Implications for stroke severity

Sohrabji

Bake

Lewis

2013

Neurochemistry International

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“…For that reason, we decided to focus our attention on the effects of aging on microvascular integrity and condition in the PAG. Apart from microvascular age-associated changes we unexpectedly discovered capillaries with a new kind of vascular aberration, hitherto not previously reported (Gerrits et al, 2010(Gerrits et al, , 2012bVeening et al, 2012). Because of the 'foamy' electron lucent character of this particular aberration, we have termed these structures as 'spumiform basement membrane degeneration', (sbmd).…”

Section: Introductionmentioning

confidence: 46%

Spumiform basement membrane aberrations in the microvasculature of the midbrain periaqueductal gray region in hamster: Rostro-caudal pathogenesis?

et al. 2013

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“…Exploring the neural substrate serving reproduction, we recently demonstrated a prominent columnar organization of nuclear estrogen receptor alpha (ER-a) immunoreactive neurons in the PAG projecting to the caudal brainstem of the female golden hamster, including nucleus retroambiguus, nucleus pararetroambiguus (NPRA) and commissural nucleus of the solitary tract (NTScom) (Gerrits et al, 2009b). The NPRA and the NTScom are part of a brainstem circuit comprising several interrelated nuclei that are subject to functional and structural plasticity and are intimately involved in the regulation of steroid hormone-dependent behaviors and their associated autonomic adaptations (Gerrits et al, 2008a(Gerrits et al, ,b, 2009b(Gerrits et al, , 2010(Gerrits et al, , 2012b.…”

Section: Introductionmentioning

confidence: 99%

“…No differences were observed between the microvascular changes occurring in the estrogen-receptive versus the estrogen-nonreceptive caudal brain stem areas of the female hamster brain. Despite commonly reported aging-associated neural and cerebrovascular degenerative changes including bloodebrain barrier (BBB) impairment (Gerrits et al, 2010(Gerrits et al, , 2012a, the animals displayed a reproductive behavioral repertoire comparable with young animals (Gerrits et al, 2009a;Veening et al, 2009). Furthermore, it was noticed that vascular degenerative aberrations like perivascular fibrosis which are commonly reported in the hippocampus of aging rats and other vertebrate species (De Jong et al, 1990; were not seen in the brainstem of the aging hamster (Veening et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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

Gerrits

Kortekaas

Weerd

et al. 2013

Neurobiology of Aging

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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.

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Microvascular changes in estrogen-α sensitive brainstem structures of aging female hamsters

Cited by 10 publications

References 28 publications

Age-related changes in brain support cells: Implications for stroke severity

Age-related changes in brain support cells: Implications for stroke severity

Spumiform basement membrane aberrations in the microvasculature of the midbrain periaqueductal gray region in hamster: Rostro-caudal pathogenesis?

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

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