• BMB Reports
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• v.52 no.2
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• pp.111-112
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• 2019

Although many studies have reported that the breakdown of the blood-brain barrier (BBB) represents one of the major pathological changes in aging, the mechanism underlying this process remains relatively unexplored. In this study, we described that acid sphingomyelinase (ASM) derived from endothelial cells plays a critical role in BBB disruption in aging. ASM levels were elevated in the brain endothelium and plasma of aged humans and mice, resulting in BBB leakage through an increase in caveolae-mediated transcytosis. Moreover, ASM caused damage to the caveolae-cytoskeleton via protein phosphatase 1-mediated ezrin/radixin/moesin dephosphorylation in primary mouse brain endothelial cells. Mice overexpressing brain endothelial cell-specific ASM exhibited acceleration of BBB impairment and neuronal dysfunction. However, genetic inhibition and endothelial specific knock-down of ASM in mice improved BBB disruption and neurocognitive impairment during aging. Results of this study revealed a novel role of ASM in the regulation of BBB integrity and neuronal function in aging, thus highlighting the potential of ASM as a new therapeutic target for anti-aging.

• Journal of Korean Neurosurgical Society
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• v.50 no.1
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• pp.45-47
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• 2011

Abnormal contrast enhancement on brain computed tomography (CT) scan after diagnostic or interventional angiography is not rare, and has known to be induced by temporary blood-brain barrier (BBB) disruption from contrast media. Furthermore, it has been regarded as clinically subtle, but reported to have no symptom or mild transient symptoms. However, we recently experienced two cases of serious BBB disruption during the acute period after coiling of an unruptured intracranial aneurysm. One patient presented with an unruptured paraclinoid internal carotid artery (ICA) aneurysm on the right and the other with an unruptured right supraclinoid ICA aneurysm. Both patients showed similar findings on immediate postembolization CT scan and clinical courses after coiling. Typical radiological, clinical characteristics of BBB disruption were described. In addition, the role of immediate postembolization CT scan are also discussed.

• Journal of Korean Neurosurgical Society
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• v.48 no.6
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• pp.524-527
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• 2010

Temporary disruption of the blood-brain barrier (BBB) after cerebral angiography is presumably caused by nonionic radiographic contrast medium (CM). We hereby report a case of 58-year-old woman who developed decreased mentality, global aphasia and aggravated right hemiparesis after cerebral angiography. Brain CT examination demonstrated gyriform enhancement throughout the left cerebral cortex and thalamus. MR diffusion did not reveal acute infarction. MR angiography did not show any stenosis, spasm or occlusion at the major cerebral vessels. Follow-up CT scan after 1 day did not show any gyriform enhancement. Worsened neurologic signs and symptoms were improved completely after 7 days. In the present study, disruption of the BBB with contrast medium after angiography seems to be the causative factor of transient neurologic deterioration.

• BMB Reports
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• v.41 no.5
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• pp.345-352
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• 2008

The cerebral microvessels possess barrier characteristics which are tightly sealed excluding many toxic substances and protecting neural tissues. The specialized blood-neural barriers as well as the cerebral microvascular barrier are recognized in the retina, inner ear, spinal cord, and cerebrospinal fluid. Microvascular endothelial cells in the brain closely interact with other components such as astrocytes, pericytes, perivascular microglia and neurons to form functional 'neurovascular unit'. Communication between endothelial cells and other surrounding cells enhances the barrier functions, consequently resulting in maintenance and elaboration of proper brain homeostasis. Furthermore, the disruption of the neurovascular unit is closely involved in cerebrovascular disorders. In this review, we focus on the location and function of these various blood-neural barriers, and the importance of the cell-to-cell communication for development and maintenance of the barrier integrity at the neurovascular unit. We also demonstrate the close relation between the alteration of the blood-neural barriers and cerebrovascular disorders.

• Science of Emotion and Sensibility
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• v.11 no.4
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• pp.565-574
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• 2008

Functions of human brain including sensibility and emotion may be affected by drugs mediated by the blood-brain barrier (BBB). The present study was performed to evaluate whether injection route, volume and concentration of mannitol could alter the degree of disruption of the BBB. Under urethane anesthesia, female Sprague-Dawley rats were infused with 20% mannitol into the right internal carotid artery (ICA). In the other group, intravenous injection of mannitol through the femoral vein was performed. Evans blue(EB) dye was used as a marker of BBB disruption. When mannitol was injected via the ICA, the content of EB dye in the ipsilateral hemisphere was markedly increased. However, the content of EB in the brain was not increased when mannitol was injected via the femoral vein, even though the volume or concentration of mannitol was increased. These results suggest that the BBB was disrupted only through ICA injection route and this may provide a useful strategy for transient opening of the BBB to control the functions of human brain.

• Archives of Pharmacal Research
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• v.29 no.4
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• pp.265-275
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• 2006

In the developing brain, capillaries are differentiated and matured into the blood-brain barrier (BBB), which is composed of cerebral endothelial cells, astrocyte end-feet, and pericytes. Since the BBB regulates the homeostasis of central nervous system (CNS), the maintenance of the BBB is important for CNS function. The disruption of the BBB may result in many brain disorders including brain tumors. However, the molecular mechanism of BBB formation and maintenance is poorly understood. Here, we summarize recent advances in the role of oxygen tension and growth factors on BBB development and maintenance, and in BBB dysfunction related with brain tumors.

• BMB Reports
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• v.49 no.5
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• pp.255-262
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• 2016

The disease known as cerebral cavernous malformations mostly occurs in the central nervous system, and their typical histological presentations are multiple lumen formation and vascular leakage at the brain capillary level, resulting in disruption of the blood-brain barrier. These abnormalities result in severe neurological symptoms such as seizures, focal neurological deficits and hemorrhagic strokes. CCM research has identified 'loss of function' mutations of three ccm genes responsible for the disease and also complex regulation of multiple signaling pathways including the WNT/β-catenin pathway, TGF-β and Notch signaling by the ccm genes. Although CCM research is a relatively new and small scientific field, as CCM research has the potential to regulate systemic blood vessel permeability and angiogenesis including that of the blood-brain barrier, this field is growing rapidly. In this review, I will provide a brief overview of CCM pathogenesis and function of ccm genes based on recent progress in CCM research.

• Biomolecules & Therapeutics
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• v.27 no.3
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• pp.290-301
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• 2019

Paeonol has neuroprotective function, which could be useful for improving central nervous system disorder. The purpose of this study was to characterize the functional mechanism involved in brain transport of paeonol through blood-brain barrier (BBB). Brain transport of paeonol was characterized by internal carotid artery perfusion (ICAP), carotid artery single injection technique (brain uptake index, BUI) and intravenous (IV) injection technique in vivo. The transport mechanism of paeonol was examined using conditionally immortalized rat brain capillary endothelial cell line (TR-BBB) as an in vitro model of BBB. Brain volume of distribution (VD) of [$^3H$]paeonol in rat brain was about 6-fold higher than that of [$^{14}C$]sucrose, the vascular space marker of BBB. The uptake of [$^3H$]paeonol was concentration-dependent. Brain volume of distribution of paeonol and BUI as in vivo and inhibition of analog as in vitro studies presented significant reduction effect in the presence of unlabeled lipophilic compounds such as paeonol, imperatorin, diphenhydramine, pyrilamine, tramadol and ALC during the uptake of [$^3H$]paeonol. In addition, the uptake significantly decreased and increased at the acidic and alkaline pH in both extracellular and intracellular study, respectively. In the presence of metabolic inhibitor, the uptake reduced significantly but not affected by sodium free or membrane potential disruption. Similarly, paeonol uptake was not affected on OCTN2 or rPMAT siRNA transfection BBB cells. Interestingly. Paeonol is actively transported from the blood to brain across the BBB by a carrier mediated transporter system.

• Korean Journal of Radiology
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• v.22 no.1
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• pp.118-130
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• 2021

Objective: This study aimed to investigate the blood-brain barrier (BBB) disruption in mild traumatic brain injury (mTBI) patients with post-concussion syndrome (PCS) using dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging and automatic whole brain segmentation. Materials and Methods: Forty-two consecutive mTBI patients with PCS who had undergone post-traumatic MR imaging, including DCE MR imaging, between October 2016 and April 2018, and 29 controls with DCE MR imaging were included in this retrospective study. After performing three-dimensional T1-based brain segmentation with FreeSurfer software (Laboratory for Computational Neuroimaging), the mean K^trans and v_p from DCE MR imaging (derived using the Patlak model and extended Tofts and Kermode model) were analyzed in the bilateral cerebral/cerebellar cortex, bilateral cerebral/cerebellar white matter (WM), and brainstem. K^trans values of the mTBI patients and controls were calculated using both models to identify the model that better reflected the increased permeability owing to mTBI (tendency toward higher K^trans values in mTBI patients than in controls). The Mann-Whitney U test and Spearman rank correlation test were performed to compare the mean K^trans and v_p between the two groups and correlate K^trans and v_p with neuropsychological tests for mTBI patients. Results: Increased permeability owing to mTBI was observed in the Patlak model but not in the extended Tofts and Kermode model. In the Patlak model, the mean K^trans in the bilateral cerebral cortex was significantly higher in mTBI patients than in controls (p = 0.042). The mean v_p values in the bilateral cerebellar WM and brainstem were significantly lower in mTBI patients than in controls (p = 0.009 and p = 0.011, respectively). The mean K^trans of the bilateral cerebral cortex was significantly higher in patients with atypical performance in the auditory continuous performance test (commission errors) than in average or good performers (p = 0.041). Conclusion: BBB disruption, as reflected by the increased K^trans and decreased v_p values from the Patlak model, was observed throughout the bilateral cerebral cortex, bilateral cerebellar WM, and brainstem in mTBI patients with PCS.

• Journal of Life Science
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• v.32 no.7
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• pp.550-566
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• 2022

Stroke is among the leading causes of death and long-term physical and cognitive disabilities worldwide, affecting an estimated 15 million people annually. The pathophysiological process of stroke is complicated by multiple and coordinated events. The breakdown of the blood-brain barrier (BBB) in people with stroke can significantly contribute to the development of ischemic brain injury. Therefore, BBB disruption is recognized as a hallmark of stroke; thus, it is important to develop novel therapeutic strategies that can protect against BBB dysfunction in ischemic stroke. Traditional medicines are composed of natural products, which represent a promising source of new ingredients for the development of conventional medicines. Indeed, several studies have shown the effectiveness of Korean medicine on stroke, highlighting the value of Korean medicinal treatment for ischemic stroke. This review summarizes the current information and underlying mechanisms regarding the ameliorating effects of the formula, decoction, herbs, and active components of traditional Korean medicine on cerebral ischemia-induced BBB disruption. These traditional medicines were shown to have protective effects on the BBB in many cellular and animal ischemia models of stroke, and experiments in various animal species, such as mice and rats. In addition, they showed brain-protective effects by protecting the BBB through the regulation of tight junction proteins and matrix metalloproteinase-9, reducing edema, neuroinflammation, and neuronal cell death. We hope that this review will help promote further investigation into the neuroprotective effects of traditional Korean medicines and stimulate the performance of clinical trials on Korean herbal medicine-derived drugs in patients with stroke.