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Povzetek: Breakdown of the blood–brain barrier (BBB) or inner blood–retinal barrier (BRB), induced by pathologically elevated levels of vascular endothelial growth factor (VEGF) or other mediators, can lead to vasogenic edema and significant clinical problems such as neuronal morbidity and mortality, or vision loss. Restoration of the barrier function with corticosteroids in the brain, or by blocking VEGF in the eye are currently the predominant treatment options for brain edema and diabetic macular edema, respectively. However, corticosteroids have side effects, and VEGF has important neuroprotective, vascular protective and wound healing functions, implying that long-term anti-VEGF therapy may also induce adverse effects. We postulate that targeting downstream effector proteins of VEGF and other mediators that are directly involved in the regulation of BBB and BRB integrity provide more attractive and safer treatment options for vasogenic cerebral edema and diabetic macular edema. The endothelial cell-specific protein plasmalemma vesicle-associated protein (PLVAP), a protein associated with trans-endothelial transport, emerges as candidate for this approach. PLVAP is expressed in a subset of endothelial cells throughout the body where it forms the diaphragms of caveolae, fenestrae and trans-endothelial channels. However, PLVAP expression in brain and eye barrier endothelia only occurs in pathological conditions associated with a compromised barrier function such as cancer, ischemic stroke and diabetic retinopathy. Here, we discuss the current understanding of PLVAP as a structural component of endothelial cells and regulator of vascular permeability in health and central nervous system disease. Besides providing a perspective on PLVAP identification, structure and function, and the regulatory processes involved, we also explore its potential as a novel therapeutic target for vasogenic cerebral edema and retinal macular edema.
Ključne besede: plasmalemma vesicle-associated protein, blood-brain barrier, blood-retinal barrier, cerebral edema, diabetic macular edema
Objavljeno v DiRROS: 06.08.2024; Ogledov: 34; Prenosov: 16
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Povzetek: Due to the diversity of underlying factors and the absence of a uniform treatment approach, diagnosis and management of patients with cerebral venous sinus thrombosis (CVST) remain a challenging task.1 CVST represents 0.5% to 1% of all strokes and affects approximately 5 patients per million every year, but has a higher frequency among younger patients. Typical acquired risk factors include recent surgery, trauma, pregnancy, postpartum state, antiphospholipid syndrome, cancer and use of oral contraceptives. Cases of inherited thrombophilia include Antithrombin III, Protein C and Protein S deficiency, factor V Leiden positivity, prothrombin gene mutation and hyperhomocisteinemia. Infection of parameningeal spaces (ears, paranasal sinuses, oral cavity, face and neck) is common cause of CVST in pediatric population but rare in adults. The symptoms of CVST are not specific. The most common complaint is headache which occurs in up to 90% of patients. Additionally, abnormal vision, any of the symptoms of stroke and seizures have been described. In the past D-dimer levels appeared to be of value as an initial screening test. A study in 2004 evaluated the sensitivity of D-dimer to be 97.1% and specificity 99.1%.8 However, later studies showed that up to 10% of patients with CVST have a normal D-dimer. As it is fast, affordable and widely available, non-contrast computed tomography (NCCT) is the most frequently performed imaging study for evaluation of patients with new headache, focal neurological abnormalities, seizure, or change in mental status. A typical imaging finding in patients with CVST is direct visualization of a hyperattenuating thrombus in the occluded sinus (dense sinus sign). Occasionally, NCCT may only show indirect signs of thrombosis, including diffuse brain edema and parenchymal hemorrhage. Sensitivity of NCCT in the diagnosis of CVST was previously considered rather poor. However, using modern multidetector row CT scanners, recent studies report higher sensitivity and specificity values. In addition, Buyck et al. suggest measurement of the venous sinus attenuation to increase the diagnostic yield of the examination. Therefore, the goal of the present study was to evaluate the diagnostic accuracy of NCCT in the diagnosis of CVST in the emergency setting
Ključne besede: cerebral venous sinus thrombosis, computed tomography, stroke, radiologija, računalniška tomografija, diagnostika, možganski venski sinusi
Objavljeno v DiRROS: 09.05.2024; Ogledov: 191; Prenosov: 167
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