Blood-brain barrier alterations in ageing and dementia

Popescu, Bogdan Ovidiu; Toescu, Emil C.; Popescu, Laurențiu M.; Băjenaru, Ovidiu; Mureșanu, Dafin F.; Schultzberg, Marianne; Bogdanović, Nenad

doi:10.1016/j.jns.2009.02.321

Cited by 203 publications

(138 citation statements)

References 117 publications

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“…In our previous studies, F3 neural stem cells (NSCs) also showed lesion tropism in both kainic acidinduced hippocampal injury and AF64A-induced cholinergic nerve injury models (Park et al, 2012a,b). Notably, leakage and increased permeability of the blood-brain barrier with ageing have been confirmed in healthy animals and humans, which might be mediated by oxidative damage following microglial activation, iron accumulation in astrocytes, and declining estrogen levels (Popescu et al, 2009;Simpson et al, 2010). Accordingly, IV-injected ADMSCs migrated into the aged brain, as confirmed in the present study.…”

Section: Discussionsupporting

confidence: 83%

Human adipose tissue‐derived mesenchymal stem cells improve cognitive function and physical activity in ageing mice

Park

Yang

Bae

et al. 2013

J of Neuroscience Research

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Brain ageing leads to atrophy and degeneration of the cholinergic nervous system, resulting in profound neurobehavioral and cognitive dysfunction from decreased acetylcholine biosynthesis and reduced secretion of growth and neurotrophic factors. Human adipose tissue-derived mesenchymal stem cells (ADMSCs) were intravenously (1 3 10 6 cells) or intracerebroventricularly (4 3 10 5 cells) transplanted into the brains of 18-month-old mice once or four times at 2-week intervals. Transplantation of ADMSCs improved both locomotor activity and cognitive function in the aged animals, in parallel with recovery of acetylcholine levels in brain tissues. Transplanted cells differentiated into neurons and, in part, into astrocytes and produced choline acetyltransferase proteins. Transplantation of ADMSCs restored microtubule-associated protein 2 in brain tissue and enhanced Trk B expression and the concentrations of brain-derived neurotrophic factor and nerve growth factor. These results indicate that human ADMSCs differentiate into neural cells in the brain microenvironment and can restore physical and cognitive functions of aged mice not only by increasing acetylcholine synthesis but also by restoring neuronal integrity that may be mediated by growth/neurotrophic factors. V V C 2013 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 83%

Human adipose tissue‐derived mesenchymal stem cells improve cognitive function and physical activity in ageing mice

Park

Yang

Bae

et al. 2013

J of Neuroscience Research

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“…Despite this, infiltration of circulating cells has been shown to occur when BBB permeability is increased. Thus T cell infiltration has been found in CNS tissues of patients with Parkinson's disease (Stone et al, 2009) and Alzheimer's disease (Schindowski et al, 2007;Togo et al, 2002) and infiltration of cells has also been reported following ischemic insult and with age (Popescu et al, 2009) and bacterial and viral infections (Stamatovic et al, 2008). In this study, increased BBB permeability was associated with increased expression of IP-10 and MCP-1.…”

Section: Discussionsupporting

confidence: 60%

“…also permit infiltration of cells (Popescu et al, 2009), although this mainly occurs under the influence of chemotactic molecules. Here we show that expression of IP-10 and MCP-1 which play a significant role in chemotaxis of peripheral cells (Babcock et al, 2003) were increased in brain tissue prepared from aged, compared with young, rats (* p Ͻ 0.05; *** p Ͻ 0.001; Student t test for independent means; Fig.…”

Section: Resultsmentioning

confidence: 99%

The age-related deficit in LTP is associated with changes in perfusion and blood-brain barrier permeability

Blau¹,

Cowley²,

O'Sullivan³

et al. 2012

Neurobiology of Aging

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In view of the increase in the aging population and the unavoidable parallel increase in the incidence of age-related neurodegenerative diseases, a key challenge in neuroscience is the identification of clinical signatures which change with age and impact on neuronal and cognitive function. Early diagnosis offers the possibility of early therapeutic intervention, thus magnetic resonance imaging (MRI) is potentially a powerful diagnostic tool. We evaluated age-related changes in relaxometry, blood flow, and blood-brain barrier (BBB) permeability in the rat by magnetic resonance imaging and assessed these changes in the context of the age-related decrease in synaptic plasticity. We report that T2 relaxation time was decreased with age; this was coupled with a decrease in gray matter perfusion, suggesting that the observed microglial activation, as identified by increased expression of CD11b, MHCII, and CD68 by immunohistochemistry, flow cytometry, or polymerase chain reaction (PCR), might be a downstream consequence of these changes. Increased permeability of the blood-brain barrier was observed in the perivascular area and the hippocampus of aged, compared with young, rats. Similarly there was an age-related increase in CD45-positive cells by flow cytometry, which are most likely infiltrating macrophages, with a parallel increase in the messenger mRNA expression of chemokines IP-10 and MCP-1. These combined changes may contribute to the deficit in long-term potentiation (LTP) in perforant path-granule cell synapses of aged animals.

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“…At the cellular level, non-pathological age-related brain changes include metabolic disarrangements, excessive production of ROS and other morphological and functional alterations in neuronal and glial cells, inducing basal glial reactivity and decreased BBB permeability [19][20][21][22]. However, although it is assumed that these characteristics influence the response to brain injury, currently most studies still use young adult animals for the analysis of post-injury inflammatory processes.…”

Section: Introductionmentioning

confidence: 99%

Decreased myeloperoxidase expressing cells in the aged rat brain after excitotoxic damage

Campuzano¹,

Castillo-Ruiz²,

Acarín³

et al. 2011

Experimental Gerontology

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Brain aging is associated to several morphological and functional alterations that influence the evolution and outcome of CNS damage. Acute brain injury such as an excitotoxic insult induces initial tissue damage followed by associated inflammation and oxidative stress, partly attributed to neutrophil recruitment and the expression of oxidative enzymes such as myeloperoxidase (MPO), among others. However, to date, very few studies have focused on how age can influence neutrophil infiltration after acute brain damage. Therefore, to evaluate the age-dependent pattern of neutrophil cell infiltration following an excitotoxic injury, intrastriatal injection of Nmethyl-D-aspartate was performed in young and aged male Wistar rats. Animals were sacrificed at different times between 12 hours post-lesion (hpl) to 14 days post-lesion (dpl). Cryostat sections were processed for myeloperoxidase (MPO) immunohistochemistry, and double labeling for either neuronal cells (NeuN), astrocytes (GFAP), perivascular macrophages (ED-2), or microglia/macrophages (tomato lectin histochemistry). Our observations showed that MPO+ cells were observed in the injured striatum from 12 hpl (when maximum values were found) until 7 dpl, when cell density was strongly diminished. However, at all survival times analyzed, the overall density of MPO+ cells was lower in the aged versus the adult injured striatum. MPO+ cells were mainly identified as neutrophils (especially at 12 hpl and 1 dpl), but it should be noted that MPO+ neurons and microglia/macrophages were also found. MPO+ neurons were most commonly observed at 12 hpl and reduced in the aged. MPO+ microglia/macrophages were the main population expressing MPO from 3 dpl, when density was also reduced in aged subjects.These results point to neutrophil infiltration as another important factor contributing to the different response of the adult and aged brain to damage, highlighting the need of using aged animals for the study of acute agerelated brain insults.

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Blood-brain barrier alterations in ageing and dementia

Cited by 203 publications

References 117 publications

Human adipose tissue‐derived mesenchymal stem cells improve cognitive function and physical activity in ageing mice

Human adipose tissue‐derived mesenchymal stem cells improve cognitive function and physical activity in ageing mice

The age-related deficit in LTP is associated with changes in perfusion and blood-brain barrier permeability

Decreased myeloperoxidase expressing cells in the aged rat brain after excitotoxic damage

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