Non-invasive assessment of blood–brain barrier (BBB) permeability using a gamma camera to detect 99technetium-gluceptate extravasation in rat brain

Esposito, Pamela; Jacobson, Stanley; Connolly, Raymond J.; Gheorghe, Daniela; Theoharides, Theoharis C.

doi:10.1016/s1385-299x(01)00104-0

Cited by 12 publications

(6 citation statements)

References 23 publications

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“…Moreover, it has been proposed that metastatic brain tumors can be promoted by stress (unavoidable in patients with cancer) [ 57 ] which activates brain MCs to disrupt the BBB via the CRH pathway [ 58 ]. This increases BBB permeability for primary cancer cells deriving from the periphery, which can subsequently infiltrate brain parenchyma and metastasize as was shown for rat mammary adenocarcinoma [ 59 ].…”

Section: Resultsmentioning

confidence: 99%

Mast cells in meningiomas and brain inflammation

Polyzoidis

Κoletsa

Panagiotidou

et al. 2015

J Neuroinflammation

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BackgroundResearch focus in neuro-oncology has shifted in the last decades towards the exploration of tumor infiltration by a variety of immune cells and their products. T cells, macrophages, B cells, and mast cells (MCs) have been identified.MethodsA systematic review of the literature was conducted by searching PubMed, EMBASE, Google Scholar, and Turning Research into Practice (TRIP) for the presence of MCs in meningiomas using the terms meningioma, inflammation and mast cells.ResultsMCs have been detected in various tumors of the central nervous system (CNS), such as gliomas, including glioblastoma multiforme, hemangioblastomas, and meningiomas as well as metastatic brain tumors. MCs were present in as many as 90 % of all high-grade meningiomas mainly found in the perivascular areas of the tumor. A correlation between peritumoral edema and MCs was found.InterpretationAccumulation of MCs in meningiomas could contribute to the aggressiveness of tumors and to brain inflammation that may be involved in the pathogenesis of additional disorders.

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Section: Resultsmentioning

confidence: 99%

Mast cells in meningiomas and brain inflammation

Polyzoidis

Κoletsa

Panagiotidou

et al. 2015

J Neuroinflammation

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“…Acute stress can activate mast cells and increase the permeability of BBB (Kempuraj et al, 2017a). However, deficiency of mast cells or inhibition of mast cell activation by mast cell stabilizer disodium cromoglycate (Cromolyn) show reduced BBB permeability indicating mast cells play an important role in stress-induced BBB disruption (Esposito et al, 2001a,b). Activated mast cells release TNF-α that can downregulate the expression of the tight junction proteins such as occludin, claudin-5, ZO-1 and adherens junction VE-cadherin (Rochfort and Cummins, 2015).…”

Section: Stress Associated Changes In the Bbb Neurovascular Unit Glmentioning

confidence: 99%

Mast Cells in Stress, Pain, Blood-Brain Barrier, Neuroinflammation and Alzheimer’s Disease

Kempuraj

Mentor

Thangavel

et al. 2019

Front. Cell. Neurosci.

109

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Mast cell activation plays an important role in stress-mediated disease pathogenesis. Chronic stress cause or exacerbate aging and age-dependent neurodegenerative diseases. The severity of inflammatory diseases is worsened by the stress. Mast cell activation-dependent inflammatory mediators augment stress associated pain and neuroinflammation. Stress is the second most common trigger of headache due to mast cell activation. Alzheimer's disease (AD) is a progressive irreversible neurodegenerative disease that affects more women than men and woman's increased susceptibility to chronic stress could increase the risk for AD. Modern life-related stress, social stress, isolation stress, restraint stress, early life stress are associated with an increased level of neurotoxic beta amyloid (Aβ) peptide. Stress increases cognitive dysfunction, generates amyloid precursor protein (APP), hyperphosphorylated tau, neurofibrillary tangles (NFTs), and amyloid plaques (APs) in the brain. Stress-induced Aβ persists for years and generates APs even several years after the stress exposure. Stress activates hypothalamic-pituitary adrenal (HPA) axis and releases corticotropin-releasing hormone (CRH) from hypothalamus and in peripheral system, which increases the formation of Aβ, tau hyperphosphorylation, and blood-brain barrier (BBB) disruption in the brain. Mast cells are implicated in nociception and pain. Mast cells are the source and target of CRH and other neuropeptides that mediate neuroinflammation. Microglia express receptor for CRH that mediate neurodegeneration in AD. However, the exact mechanisms of how stress-mediated mast cell activation contribute to the pathogenesis of AD remains elusive. This mini-review highlights the possible role of stress and mast cell activation in neuroinflammation, BBB, and tight junction disruption and AD pathogenesis.

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“…A modification of this method used 99technetium-gluceptate with a γ camera instead of a fluorescent tracer. 29 An advantage of assessing BBB disruption by fluorescence microscopy is that pharmaceutical agents can be given systemically or topically, and their effect on the BBB can be measured in real time. This method can be combined with measurement of evoked neuronal responses permitting correlation of BBB disruption with neuronal activity.…”

Section: Strokementioning

confidence: 99%

Assessment of Blood–Brain Barrier Disruption in Stroke

Kassner

Merali

2015

Stroke

126

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T he disease burden of acute ischemic stroke (AIS) is rising in the United States and Canada. It is estimated that in the United States 795 000 people have a stroke each year, which amounts to $34 billion in medical expenses and lost productivity.1 Recent trials have shown the potential benefit of procedural thrombectomy in the management of AIS. 2 However, despite substantial research expenditures over the past 2 decades, there have been no new pharmacological agents for the initial treatment of AIS since the approval of recombinant tissue-type plasminogen activator in 1996. Recently, the role of the blood-brain barrier (BBB) in the pathogenesis of AIS has emerged as a focus for new therapeutic strategies. After the onset of AIS, the BBB is rapidly disrupted and this disruption persists for days through the acute and early subacute phases of AIS. The disruption of the BBB can be quantified as an increase in the permeability of the BBB (Figure 1). 4 In the setting of AIS, disruption of the BBB is thought to be a precursor to serious clinical consequences such as hemorrhagic transformation (HT), 5-7 which refers to the development of a hemorrhage within the ischemic brain tissue. Current research is attempting to elucidate the mechanisms of BBB disruption after AIS and develop therapeutic strategies to mitigate the clinical consequences of BBB disruption.Given these developments, a greater number of preclinical and clinical studies are incorporating assessment of BBB disruption into their study designs. Although assessment of BBB disruption may once have been technically difficult, a plethora of methods now exist to assess BBB disruption with relative ease in animal models and humans. When taken together, these methods cover a wide range of temporal and spatial resolutions and permit simultaneous assessment of cell morphology, protein expression and localization, cell electrophysiology, and gross neurological function. An awareness of the specifications and limitations of the methods of assessing BBB disruption is necessary to design effective studies and evaluate the literature.In the present review, we summarize the available methods of assessing BBB permeability in animal models and humans. We strive to highlight the relative strengths and weaknesses of these methods and provide suggestions for study design in stroke research. Finally, we discuss recent translational developments in assessing BBB disruption for the treatment of AIS. Ex Vivo Assessment of BBB DisruptionThe pioneering experiments of Max Lewandowsky first defined the BBB as a dynamic barrier separating the intravascular and extravascular compartments. This laid the groundwork for current methods of assessing BBB disruption in AIS animal models and human trials.8 All methods of assessing BBB disruption are common in their use of tracers, which can be either endogenous if they are naturally found in the blood or exogenous if introduced into the circulation by the experimenter. Table I in the online-only Data Supplement summarizes methods of ass...

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Non-invasive assessment of blood–brain barrier (BBB) permeability using a gamma camera to detect 99technetium-gluceptate extravasation in rat brain

Cited by 12 publications

References 23 publications

Mast cells in meningiomas and brain inflammation

Mast cells in meningiomas and brain inflammation

Mast Cells in Stress, Pain, Blood-Brain Barrier, Neuroinflammation and Alzheimer’s Disease

Assessment of Blood–Brain Barrier Disruption in Stroke

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