• Journal of Interdisciplinary Genomics
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• v.2 no.2
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• pp.20-25
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• 2020

Mucopolysaccharidosis type III (MPS III or Sanfilippo syndrome) is a multisystem lysosomal storage disease that is inherited in an autosomal recessive manner. It consists of four subtypes (MPS IIIA, B, C, and D), each characterized by the deficiency of different enzymes that catalyze the metabolism of the glycosaminoglycan heparan sulfate at the lysosomal level. The typical clinical manifestation of MPS III includes progressive central nervous system (CNS) degeneration with accompanying systemic manifestations. Disease onset is typically before the age of ten years and death usually occurs in the second or third decade due to neurological regression or respiratory tract infections. However, there is currently no treatment for CNS symptoms in patients with MPS III. Invasive and non-invasive techniques that allow drugs to pass through the blood brain barrier and reach the CNS are being tested and have proven effective. In addition, the application of genistein treatment as a substrate reduction therapy is in progress.

• Interdisciplinary Bio Central
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• v.2 no.4
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• pp.9.1-9.5
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• 2010

Many neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, are devastating disorders that affect millions of people worldwide. However, the number of therapeutic options remains severely limited with only symptomatic management therapies available. With the better understanding of the pathogenesis of neurodegenerative diseases, discovery efforts for disease-modifying drugs have increased dramatically in recent years. However, the process of translating basic science discovery into novel therapies is still lagging behind for various reasons. The task of finding new effective drugs targeting central nervous system (CNS) has unique challenges due to blood-brain barrier (BBB). Furthermore, the relatively slow progress of neurodegenerative disorders create another level of difficulty, as clinical trials must be carried out for an extended period of time. This review is intended to provide molecular and cell biologists with working knowledge and resources on CNS drug discovery and development.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.2
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• pp.277-277
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• 2017

• Proceedings of the PSK Conference
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• 2002.04a
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• pp.178.2-179
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• 2002

• Journal of Preventive Medicine and Public Health
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• v.45 no.6
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• pp.344-352
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• 2012

Mercury is a toxic and non-essential metal in the human body. Mercury is ubiquitously distributed in the environment, present in natural products, and exists extensively in items encountered in daily life. There are three forms of mercury, i.e., elemental (or metallic) mercury, inorganic mercury compounds, and organic mercury compounds. This review examines the toxicity of elemental mercury and inorganic mercury compounds. Inorganic mercury compounds are water soluble with a bioavailability of 7% to 15% after ingestion; they are also irritants and cause gastrointestinal symptoms. Upon entering the body, inorganic mercury compounds are accumulated mainly in the kidneys and produce kidney damage. In contrast, human exposure to elemental mercury is mainly by inhalation, followed by rapid absorption and distribution in all major organs. Elemental mercury from ingestion is poorly absorbed with a bioavailability of less than 0.01%. The primary target organs of elemental mercury are the brain and kidney. Elemental mercury is lipid soluble and can cross the blood-brain barrier, while inorganic mercury compounds are not lipid soluble, rendering them unable to cross the blood-brain barrier. Elemental mercury may also enter the brain from the nasal cavity through the olfactory pathway. The blood mercury is a useful biomarker after short-term and high-level exposure, whereas the urine mercury is the ideal biomarker for long-term exposure to both elemental and inorganic mercury, and also as a good indicator of body burden. This review discusses the common sources of mercury exposure, skin lightening products containing mercury and mercury release from dental amalgam filling, two issues that happen in daily life, bear significant public health importance, and yet undergo extensive debate on their safety.

• Biomolecules & Therapeutics
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• v.8 no.2
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• pp.194-198
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• 2000

Taurine, 2-aminoethanesulfonic acid is widely distributed in animal tissues and has a variety of bio-logical activities. A recent worldwide study demonstrated beneficial effects of taurine on aging and age-associated disorders. In general, taurine levels in the brain decease when an animal is subjected to pathologic conditions such as ischemia-anoxia and seizure. But the taurine levles tend to increase in the brain in hypertensive state. In the present study, the blood-brain barrier (BBB) transport of [$^3$H]taurine was compared between spontaneously hypertensive rats (SHR) and normotensive Sprague-Dawley rats (SD) using intravenous injection technique in vivo. We also obtained pharmacokinetic parameters of plasma volume maker, [$^{14}$ C] sucrose and [$^3$H]taurine after inject to rats simulatenously. BBB permeability surface area product (PS) value of [$^3$H]taurine in SHR (16$\pm$2.9$\times$10$^{-3}$ ml/min/g) was significantly higher than that in SD (7.4$\pm$0.8$\times$10$^{-3}$ ml/min/g). There is also significant difference for brain uptake of [$^3$H]taurine between SHR (0.195$\pm$0.031%ID/g) and SD (0.058$\pm$0.003% ID/g). This is due to difference of area under the plasma concentration-time curve (AUC) and that of total clearance (Class) between SHR and SD. No significant difference was indicated from other organ uptakes such as lung, heart, liver SHR and SD. But also kidney uptake was much higher in SHR. In conclusion, [$^3$H]taurine in plasma was slowly eliminated in SHR than in SD and uptake of [$^3$H]taurine in SHR is much higher than that of SD. This results suggest increased taurine level in the brain in hypertension state have an any effect on the brain uptake of taurine.

• 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 Ginseng Research
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• v.45 no.5
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• pp.599-609
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• 2021

Ginseng has long been considered as an herbal medicine. Recent data suggest that ginseng has antiinflammatory properties and can improve learning- and memory-related function in the central nervous system (CNS) following the development of CNS neuroinflammatory diseases such as Alzheimer's disease, cerebral ischemia, and other neurological disorders. In this review, we discuss the role of ginseng in the neurovascular unit, which is composed of endothelial cells surrounded by astrocytes, pericytes, microglia, neural stem cells, oligodendrocytes, and neurons, especially their blood-brain barrier maintenance, anti-inflammatory effects and regenerative functions. In addition, cell-cell communication enhanced by ginseng may be attributed to regeneration via induction of neurogenesis and angiogenesis in CNS diseases. Thus, ginseng may have therapeutic potential to exert cognitive improvement in neuroinflammatory diseases such as stroke, traumatic brain injury, multiple sclerosis, Parkinson's disease, and Alzheimer's disease.

• Journal of Pharmaceutical Investigation
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• v.29 no.2
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• pp.87-92
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• 1999

Drug delivery to the brain may be achieved by producing chimeric peptide, attaching the drug to protein 'vectors' which are transported into the brain from the blood by a receptor-mediated transcytosis through the blood-brain barrier (BBB). Since the BBB expresses high concentrations of transferrin receptor, and it was reported that anti-transferrin receptor mouse monoclonal antibody (OX26) undergoes transcytosis through the BBB, it is logical to assume that a drug delivery system via transferrin receptor-mediated transcytosis is a promising strategy. In the present study, therefore, we tested feasibility of several OX26 based vectors for the brain delivery of a model drug. Avidin-based delivery vectors such as OX26-streptavidin (OX26-SA), OX26-neutralite avidin (OX26-NLA) were chemically synthesized vectors and OX26 immunoglobulin G 3 type $C_{H}3$ fusion avidin $(OX26\;IgG3C_H3-AV)$ was genetically engineered. To improve the efficiency of producing chimeric peptide, we used avidin-biotin technology. Pharmacokinetics of $[^3H]biotin$ bound to OX26-SA, OX26-NLA and $OX26\;IgG3C_H3-AV$ was determined by intravenous injection technique, and their stabilities in plasma were analyzed using HPLC. The brain delivery of $[^3H]biotin$ bound to OX26-SA, OX26-NLA and OX26\;$IgG3C_{H}3-AV$ (expressed as %ID/g brain) was $0.22{\pm}0.01$, $0.18{\pm}0.01$ and $0.25{\pm}0.09$, respectively. The areas under the plasma concentration versus time curve (AUC) for OX26-SA, OX26-NLA, $OX26\;IgG3C_H3-AV$ from time zero to 60 min were $209{\pm}10$, $195{\pm}9$, $134{\pm}29\;%ID\;min/ml$ respectively and their total clearances $(CL_{tot})$ were $1.00{\pm}0.09$, $1.08{\pm}0.07$ and $1.54{\pm}0.29\;ml/min/kg$, espectively. These results showed that these vectors possess preferable pharmaceutical (e.g., resonable stability) and pharmacokinetics (e.g., significant brain uptake and enhanced AUC) for brain delivery. Therefore, these vectors may be broadly useful in the brain delivery of drugs that are not transported into the brain to a significant extent.

• Biomolecules & Therapeutics
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• v.20 no.3
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• pp.293-298
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• 2012

The purpose of this study was to investigate the modification of expression and functionality of the drug transporter P-glycoprotein (P-gp) by tumor necrosis factor-alpha (TNF-${\alpha}$) and interferon-gamma (IFN-${\gamma}$) at the blood-brain barrier (BBB). We used immortalized human brain microvessel endothelial cells (iHBMEC) and primary human brain microvessel endothelial cells (pHBMEC) as in vitro BBB model. To investigate the change of p-gp expression, we carried out real time PCR analysis and Western blotting. To test the change of p-gp activity, we performed rhodamin123 (Rh123) accumulation study in the cells. In results of real time PCR analysis, the P-gp mRNA expression was increased by TNF-${\alpha}$ or IFN-${\gamma}$ treatment for 24 hr in both cell types. However, 48 hr treatment of TNF-${\alpha}$ or IFN-${\gamma}$ did not affect P-gp mRNA expression. In addition, co-treatment of TNF-${\alpha}$ and IFN-${\gamma}$ markedly increased the P-gp mRNA expression in both cells. TNF-${\alpha}$ or IFN-${\gamma}$ did not influence P-gp protein expression whatever the concentration of cytokines or duration of treatment in both cells. However, P-gp expression was increased after treatments of both cytokines together in iHBMEC cells only compared with untreated control. Furthermore, in both cell lines, TNF-${\alpha}$ or IFN-${\gamma}$ induced significant decrease of P-gp activity for 24 hr treatment. And, both cytokines combination treatment also decreased significantly P-gp activity. These results suggest that P-gp expression and function at the BBB is modulated by TNF-${\alpha}$ or/and IFN-${\gamma}$. Therefore, the distribution of P-gp depending drugs in the central nervous system can be modulated by neurological inflammatory diseases.