• Biomolecules & Therapeutics
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• v.30 no.1
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• pp.55-63
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• 2022

Oleanolic acid (OA), a natural pentacyclic triterpenoid, has been reported to exert protective effects against several neurological diseases through its anti-oxidative and anti-inflammatory activities. The goal of the present study was to evaluate the therapeutic potential of OA against acute and chronic brain injuries after ischemic stroke using a mouse model of transient middle cerebral artery occlusion (tMCAO, MCAO/reperfusion). OA administration immediately after reperfusion significantly attenuated acute brain injuries including brain infarction, functional neurological deficits, and neuronal apoptosis. Moreover, delayed administration of OA (at 3 h after reperfusion) attenuated brain infarction and improved functional neurological deficits during the acute phase. Such neuroprotective effects were associated with attenuation of microglial activation and lipid peroxidation in the injured brain after the tMCAO challenge. OA also attenuated NLRP3 inflammasome activation in activated microglia during the acute phase. In addition, daily administration of OA for 7 days starting from either immediately after reperfusion or 1 day after reperfusion significantly improved functional neurological deficits and attenuated brain tissue loss up to 21 days after the tMCAO challenge; these findings supported therapeutic effects of OA against ischemic stroke-induced chronic brain injury. Together, these findings showed that OA exerted neuroprotective effects against both acute and chronic brain injuries after tMCAO challenge, suggesting that OA is a potential therapeutic agent to treat ischemic stroke.

• Biomolecules & Therapeutics
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• v.10 no.1
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• pp.37-42
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• 2002

Brain drug targeting through the blood-brain barrier (BBB) in vivo is possible with peptidornirnetic monoclonal antibodies that undergo receptor-mediated transcytosis through the BBB. Monoclonal antibody to the rat transferrin receptor, such as the OX26 was studied in rats as a transport vector through BBB on the transferrin receptor. But, OX26 is not an effective brain delivery vector in mouse. In the present studies, rat monoclonal antibody, 8D3 to the mouse transferrin receptor were evaluated for brain drug targeting vector intransgenic mouse model. Pharrnacokinetic parameters in plasma and organ uptakes were determined at varioustimes after i.v. bolus injection of [$^{}125}I$] 8D3 in Balb/c mice. Brain uptake of [$^{}125}I$] 8D3 was also studied with an internal carotid artery perfusioncapillary depletion method. After i.v. injection of [$^{}125}I$] 8D3, plasma concentrations declined biexponentially with elimination half lift of approximately 2.2 hours. Brain uptake of [$^{}125}I$] 8D3 was $0.50{\pm}0.09$ persent of injected dose per g brain after 2 hours i.v. injection. After perfusion 5 min the apparent volume of distibution of [$^{}125}I$] 8D3 in brain was $22.3 {\mu}l/g,$ which was 4.8 fold higher than the intravascular volume. These studies indicate rat monoclonal antibody to the mouse transferrin receptor, 8D3 may be used for brain drug targeting vector in mice.

• Proceedings of the Korean Society of Toxicology Conference
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• 2006.11a
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• pp.55-64
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• 2006

The fetal central nervous system (CNS) is sensitive to diverse environmental factors, such as alcohol, heavy metals, irradiation, mycotoxins, neurotransmitters, and DNA damage, because a large number of processes occur during an extended period of development. Fetal neural damage is an important issue affecting the completion of normal CNS development. As many concepts about the brain development have been recently revealed, it is necessary to compare the mechanism of developmental abnormalities induced by extrinsic factors with the normal brain development. To clarify the mechanism of fetal CNS damage, we used one experimental model in which 5-azacytidine (5AZC), a DNA damaging and demethylating agent, was injected to the dams of rodents to damage the fetal brain. 5AzC induced cell death (apoptosis)and cell cycle arrest in the fetal brain, and it lead to microencephaly in the neonatal brain. We investigated the mechanism of apoptosis and cell cycle arrest in the neural progenitor cells in detail, and demonstrated that various cell cycle regulators were changed in response to DNA damage. p53, the guardian of genome, played a main role in these processes. Further, using DNA microarray analysis, tile signal cascades of cell cycle regulation were clearly shown. Our results indicate that neural progenitor cells have the potential to repair the DNA damages via cell cyclearrest and to exclude highly affected cells through the apoptotic process. If the stimulus and subsequent DNA damage are high, brain development proceeds abnormally and results in malformation in the neonatal brain. Although the mechanisms of fetal brain injury and features of brain malformation afterbirth have been well studied, the process between those stages is largely unknown. We hypothesized that the fetal CNS has the ability to repair itself post-injuring, and investigated the repair process after 5AZC-induced damage. Wefound that the damages were repaired by 60 h after the treatment and developmental processes continued. During the repair process, amoeboid microglial cells infiltrated in the brain tissue, some of which ingested apoptotic cells. The expressions of genes categorized to glial cells, inflammation, extracellular matrix, glycolysis, and neurogenesis were upregulated in the DNA microarray analysis. We show here that the developing brain has a capacity to repair the damage induced by the extrinsic stresses, including changing the expression of numerous genes and the induction of microglia to aid the repair process.

• Biomolecules & Therapeutics
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• v.19 no.2
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• pp.224-230
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• 2011

In order to develop silk peptide (SP) preparations possessing cognition-enhancing effect, several candidates were screened through in vitro assays, and their effectiveness was investigated in facilitated brain aging model rats. Incubation of brain acetyl-cholinesterase with SP-PN (1-1,000 ${\mu}g/ml$) led to inhibition of the enzyme activity up to 35%, in contrast to a negligible effect of SP-NN. The expression of choline acetyltransferase (ChAT) mRNA of neural stem cells expressing ChAT gene (F3.ChAT) was increased by 24-hour treatment with 10 and 100 ${\mu}g/ml$ SP-NN (1.35 and 2.20 folds) and SP-PN (2.40 and 1.34 folds). Four-week subcutaneous injections with D-galactose (150 mg/kg) increased activated hippocampal astrocytes to 1.7 folds (a marker of brain injury and aging), decreased acetylcholine concentration in cerebrospinal fluid by 45-50%, and thereby impaired learning and memory function in passive avoidance and water-maze performances. Oral treatment with SP preparations (50 or 300 mg/kg) for 5 weeks from 1 week prior to D-galactose injection exerted recovering activities on acetylcholine depletion and brain injury/aging as well as cognitive deficit induced by D-galactose. The results indicate that SP preparations restore cognitive functions of facilitated brain aging model rats by increasing the release of acetylcholine, in addition to neuroprotective activity.

• Proceedings of the Korean Society for the Gifted Conference
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• 2003.05a
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• pp.137-138
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• 2003

Understanding how and why people differ is a fundamental, if distant, goal of research efforts to bridge psychological and biological levels of analysis. General fluid intelligence (gF) is a major dimension of individual differences and refers to reasoning and novel problemsolving ability. A conceptual integration of evidence from cognitive (behavioral) and anatomical studies suggeststhat gF should covary with both task performance and neural activity in specific brain systems when specific cognitive demands are present, with the neural activity mediating the relation between gF and performance. Direct investigation of this possibility will be a critical step toward a mechanistic model of human intelligence. In turn, a mechanistic model might suggest ways to enhance gF through targeted behavioral or neurobiological intervent ions, We formed two different groups as subjects based on their scholarly attainments. Each group consists of 20 volunteers(aged 16-17 years, right-handed males) from the National Gifted School and a local high school respectively. To test whether individual differences in general intelligence are mediated at a neural level, we first assessed intellectual characteristics in 40 subjects using standard intelligence tests (Raven's Advanced Progressive Matrices, Wechsler Adult Intelligence Scale, Torrance Tests of Creative Thinking) administered outside of the MR scanner. We then used functional magnetic resonance imaging (fMRl) to measure task-related brain activity as participants performed three different kinds of computerized reasoning tasks that were intended to activate the relevant neural systems. To examine the difference of neural activity according to discrepancy in general intelligence, we compared the brain activity of both extreme groups (each, n=10) of the participants based on the standard intelligence test scores. In contrast to the common expectation, there was no significant difference of brain region involved in high-g tasks between both groups. Random effect analysis exhibited that lateral prefrontal, anterior cingulate and parietal cortex are associated with gF. Despite very different task contents in the three high-g-low-g contrasts, recruitment of multiple regions is markedly similar in each case, However, on the task with high 9F correlations, the Prodigy group, (intelligence rank: >99%) showed higher task-related neural activity in several brain regions. These results suggest that the relationship between gF and brain activity should be stronger under high-g conditions than low-g conditions.

• Journal of The Korean Association For Science Education
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• v.29 no.8
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• pp.990-1010
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• 2009

To derive brain-based evolutionary educational principles, this study examined the studies on the structural and functional characteristics of human brain, the biological evolution occurring between- and within-organism, and the evolutionary attributes embedded in science itself and individual scientist's scientific activities. On the basis of the core characteristics of human brain and the framework of universal Darwinism or universal selectionism consisted of generation-test-retention (g-t-r) processes, a Model of Brain-based Evolutionary Scientific Teaching for Learning (BEST-L) was developed. The model consists of three components, three steps, and assessment part. The three components are the affective (A), behavioral (B), and cognitive (C) components. Each component consists of three steps of Diversifying $\rightarrow$ Emulating (Executing, Estimating, Evaluating) $\rightarrow$ Furthering (ABC-DEF). The model is 'brain-based' in the aspect of consecutive incorporation of the affective component which is based on limbic system of human brain associated with emotions, the behavioral component which is associated with the occipital lobes performing visual processing, temporal lobes performing functions of language generation and understanding, and parietal lobes, which receive and process sensory information and execute motor activities of the body, and the cognitive component which is based on the prefrontal lobes involved in thinking, planning, judging, and problem solving. On the other hand, the model is 'evolutionary' in the aspect of proceeding according to the processes of the diversifying step to generate variants in each component, the emulating step to test and select useful or valuable things among the variants, and the furthering step to extend or apply the selected things. For three components of ABC, to reflect the importance of emotional factors as a starting point in scientific activity as well as the dominant role of limbic system relative to cortex of brain, the model emphasizes the DARWIN (Driving Affective Realm for Whole Intellectual Network) approach.

• ETRI Journal
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• v.38 no.3
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• pp.487-493
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• 2016

Two new methods are proposed for an unsupervised adaptation of a language model (LM) with a single sentence for automatic transcription tasks. At the training phase, training documents are clustered by a method known as Latent Dirichlet allocation (LDA), and then a domain-specific LM is trained for each cluster. At the test phase, an adapted LM is presented as a linear mixture of the now trained domain-specific LMs. Unlike previous adaptation methods, the proposed methods fully utilize a trained LDA model for the estimation of weight values, which are then to be assigned to the now trained domain-specific LMs; therefore, the clustering and weight-estimation algorithms of the trained LDA model are reliable. For the continuous speech recognition benchmark tests, the proposed methods outperform other unsupervised LM adaptation methods based on latent semantic analysis, non-negative matrix factorization, and LDA with n-gram counting.

• The Journal of the Korea Contents Association
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• v.12 no.9
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• pp.270-279
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• 2012

This paper explores CT findings of a rabbit brain infection model injected with Escherichia coli and investigates the changes in Hounsfield unit (HU) of arterial blood over time. The brain infection model was produced by injecting E. coli $1{\times}10^7$ CFU/ml, 0.1 ml through the burr hole in the calvarium; 2~3 mm in depth from the dura mater, and contrast-enhanced CT, dynamic CT and arterial blood CT images were gained. It was found that various brain infections such as brain abscess, ventriculitis and meningitis. The CT image of brain abscess showed a typical pattern which the peripheral area was strongly contrast-enhanced while the center was weakly contrast-enhanced. The CT image of ventriculitis showed a strong contrast-enhancement along the lateral ventricle wall, and the CT image of meningitis showed a strong contrast-enhancement in the area between the telencephalon and the diencephalon. In dynamic CT images, the HU value of the infection core before injecting contrast medium was $31.01{\pm}3.55$. By 10 minutes after the injection, the value increased gradually to $40.36{\pm}3.76$. The HU value in the areas of the marginal rim where was hyper-enhanced showed $47.23{\pm}3.12$ before contrast injection, and it increased to $63.59{\pm}3.31$ about 45 seconds after the injection. In addition, the HU value of the normal brain tissue opposite to the E. coli. injected brain was $39.01{\pm}3.24$ before the injection, but after the contrast injection, the value increased to $49.01{\pm}4.29$ in about 30 seconds, and then it showed a gradual decline. In the arterial blood CT, the HU value before the contrast injection was $87.78{\pm}6.88$, and it increased dramatically between 10 to 30 seconds until it reached a maximum value of $749.13{\pm}98.48$. Then it fell sharply to $467.85{\pm}62.98$ between 30 seconds to 45 seconds and reached a plateau by 60 seconds. Later, the value showed a steady decrease and indicated $188.28{\pm}25.03$ at 20 minutes. Through this experiment, it was demonstrated that the brain infection model can be produced by injecting E. coli., and the characteristic of the infection model can be well observed with contrast-enhanced CT scan. The dynamic CT scan showed that the center of the infection was gradually contrast-enhanced, whereases the peripheral area was rapidly contrast-enhanced and then slowly decreased. As for arterial blood, it increased significantly between 10 seconds to 30 seconds after the contrast medium injection and decreased gradually after reaching a plateau.

• 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.

• Proceedings of the KOSOMBE Conference
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• v.1997 no.11
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• pp.213-217
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• 1997

In this study, three-dimensional inite element model was developed and analyzed or DAI using ABAQUS. To verify the developed FE model, simulated results were compared to experimental results of human cadaver by Nahum et. al. (1977). The effect of acceleration pattern and accelerating duration time or DAI was analyzed by means of maximum shear stress and pressure distribution. DAI was favored or angular acceleration rather than linear acceleration, and occured in brain stem, pons and midbrain easily as accelerating duration time was increased.