• Physical Therapy Korea
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• v.12 no.3
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• pp.11-21
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• 2005

The present study was aimed at investigating the effect of swimming training on brain function after focal cerebral ischemia in rats. Therefore, this study was examined on neurogenesis in dentate gyrus of hippocampus using 5-bromo-2'-deoxyuridine (BrdU) to label proliferating cells and assessed the neurological response following focal cerebral ischemia in rats using neurological motor behavioral test. In an observer-blinded fashion, twenty male Sprague-Dawley (280~310 g, 7 weeks old) rats were divided into four groups: MCAO plus swimming group (ME, $n_1$=5), MCAO plus control group (MC, $n_2$=5), SHAM plus swimming group (SE, $n_3$=5), SHAM plus control group (SC, $n_4$=5). The results of this study were as follows: 1) The limb placing time before and after swimming in the ME group were significantly longer than the MC group (p<.05), the SE group were significantly longer than the SC group (p<.01). 2) The balance beam scores before and after swimming in the ME group was higher than the SE group, the MC group was higher than the SC group but was not significantly different (p>.001). 3) The foot fault index before and after swimming training in ME group was significantly lower (i.e., improved) than the MC group (p<.001) and the SE group (p<.001), the SE group was significantly lower (i.e., improved) than the SC group (p<.001). 4) The mean number of BrdU-positive cells in the dentate gyrus in the ME group was significantly higher than the MC group (p<.001) and the SE group (p<.01). The MC group and the SE group was significantly higher than the SC group (p<.001). 5) There was significantly correlation between limb placing time and number of BrdU-positive cells on swimming training, there was positive correlation (r=.807, p<.0001) and between foot fault index and BrdU-positive cells number, there was negative correlation (r=-.503, p<.05). However, between balance beam scores and BrdU-positive cells number, there was no correlation. In conclusion, the present study demonstrates that the role of swimming training improves behavioral motor function probably by enhancing cell proliferation in that hippocampus. This study provides a model for investigating the stroke rehabilitation that underlies neurogenesis and functional ability.

• Korean Journal of Food Science and Technology
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• v.52 no.1
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• pp.60-66
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• 2020

This study examined the antioxidant activity and neuroprotective effects of ethanol extracts obtained from Diospyros kaki core (DCE). The total polyphenol and flavonoid contents in DCE was 786.47±15.27 and 31.14±0.82 mg/g, respectively. In addition, DCE exhibited a dose-dependent induction of radical scavenging activity, determined by 1,1-diphenyl-picrylhydrazyl (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonicacid) (ABTS), ferric reducing antioxidant power (FRAP), and reducing power assays. The viability of HT22 hippocampal cells was examined to investigate the neuroprotective effect of DCE. DCE treatment did not induce cytotoxicity at concentrations below 1,000 ㎍/mL. Additionally, DCE treatment in the background of H₂O₂ induce oxidative stress revealed a significant increase in the survival rat, indicated by increased SOD activity and decreased levels of MDA, a lipid peroxidation product. Therefore, the results suggest that DCE can be used as a source of natural antioxidants source and a therapeutic agent for the treatment of brain disorders induced by oxidative stress and neuronal damage.

• Biomolecules & Therapeutics
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• v.22 no.1
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• pp.17-26
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• 2014

${\alpha}$-Asarone exhibits a number of pharmacological actions including neuroprotective, anti-oxidative, anticonvulsive, and cognitive enhancing action. The present study investigated the effects of ${\alpha}$-asarone on pro-inflammatory cytokines mRNA, microglial activation, and neuronal damage in the hippocampus and on learning and memory deficits in systemic lipopolysaccharide (LPS)-treated C57BL/6 mice. Varying doses of ${\alpha}$-asarone was orally administered (7.5, 15, or 30 mg/kg) once a day for 3 days before the LPS (3 mg/kg) injection. ${\alpha}$-Asarone significantly reduced TNF-${\alpha}$ and IL-$1{\beta}$ mRNA at 4 and 24 hours after the LPS injection at dose of 30 mg/kg. At 24 hours after the LPS injection, the loss of CA1 neurons, the increase of TUNEL-labeled cells, and the up-regulation of BACE1 expression in the hippocampus were attenuated by 30 mg/kg of ${\alpha}$-asarone treatment. ${\alpha}$-Asarone significantly reduced Iba1 protein expression in the hippocampal tissue at a dose of 30 mg/kg. ${\alpha}$-Asarone did not reduce the number of Iba1-expressing microglia on immunohistochemistry but the average cell size and percentage areas of Iba1-expressing microglia in the hippocampus were significantly decreased by 30 mg/kg of ${\alpha}$-asarone treatment. In the Morris water maze test, ${\alpha}$-asarone significantly prolonged the swimming time spent in the target and peri-target zones. ${\alpha}$-Asarone also significantly increased the number of target heading and memory score in the Morris water maze. The results suggest that inhibition of pro-inflammatory cytokines and microglial activation in the hippocampus by ${\alpha}$-asarone may be one of the mechanisms for the ${\alpha}$-asarone-mediated ameliorating effect on memory deficits.

• Toxicological Research
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• v.6 no.2
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• pp.205-213
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• 1990

The regulation of neurotoxicants has usually been based upon setting reference doses by dividing a no observed adverse effect level (NOAEL) by uncertainty factors that theoretically account for interspecies and intraspecies extraploation of experimental results in animals to humans. Recently, we have proposed a four-step alternative procedure which provides quantitative estimates of risk as a function of dose. The first step is to establish a mathematical relationship between a biological effect or biomarker and the dose of chemical administered. The second step is to determine the distribution (variability) of individual measurements of biological effects or their biomarkers about the dose response curve. The third step is to define an adverse or abnormal level of a biological effect or biomarker in an untreated population. The fourth and final step is to combine the information from the first three steps to estimate the risk (proportion of individuals exceeding on adverse or abnormal level of a biological effect or biomarker) as a function of dose. The primary purpose of this report is to enhance the certainty of the first step of this procedure by improving our understanding of the relationship between a biomarker and dose of administered chemical. Several factors which need to be considered include: 1) the pharmacokinetics of the parent chemical, 2) the target tissue concentrations of the parent chemical or its bioactivated proximate toxicant, 3) the uptake kinetics of the parent chemical or metabolite into the target cell(s) and/or membrane interactions, and 4) the interaction of the chemical or metabolite with presumed receptor site(s). Because these theoretical factors each contain a saturable step due to definitive amounts of required enzyme, reuptake or receptor site(s), a nonlinear, saturable dose-response curve would be predicted. In order to exemplify this process, effects of the neurotoxicant, methlenedioxymethamphetamine (MDMA), were reviewed and analyzed. Our results and those of others indicate that: 1) peak concentrations of MDMA and metabolites are ochieved in rat brain by 30 min and are negligible by 24 hr, 2) a metabolite of MDMA is probably responsible for its neurotoxic effects, and 3) pretreatment with monoamine uptake blockers prevents MDMA neurotoxicity. When data generated from rats administerde MDMA were plotted as bilolgical effect (decreases in hippocampal serotonin concentrations) versus dose, a saturation curve best described the observed relationship. These results support the hypothesis that at least one saturable step is involved in MDMA neurotoxicity. We conclude that the mathematical relationship between biological effect and dose of MDMA, the first step of our quantitative neurotoxicity risk assessment procedure, should reflect this biological model information generated from the whole of the dose-response curve.

• Journal of Sasang Constitutional Medicine
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• v.27 no.2
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• pp.270-287
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• 2015

Objectives To evaluate the neuroprotective effects of modified Yuldahanso-tang (MYH) in a Parkinson's disease mouse model. Methods 1) Four groups (each of 8 rats per group) were used in this study. 2) The neuroprotective effect of MYH was examined in a Parkinson's disease mouse model. C57BL/6 mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg/day), intraperitoneal (i.p.) for 5 days. 3) The brains of 2 mice per group were removed and frozen at $-20^{\circ}C$, and the striatum-substantia nigra part was seperated. The protein volume was measured by Bradford method following Bio-Rad protein analyzing kit. Using mouse/Rat Dopamine ELISA Assay Kit. 4) The brains of 2 mice per group were separated and removed. TH-immunohistochemical was examined in the MPTP-induced Parkinson's disease mice to evaluate the neuroprotective effects of MYH on ST and SNpc. 5) Two mice out of each group were anesthetized and skulls were opened from occipital to frontal direction to take out the brains. The brains added TTC solution for 20 minutes for staining. 6) The water tank used for morris water maze test was filled with $28^{\circ}C$ water, and a round platform of 10cm in diameter was installed for mice to step on. The study was carried out once a day within 30 seconds, keep exercising to step on the platform in the pool. 7) The brains of two mice out of each group were fixed in 10% formaldehyde solution and paraphillin substance was infiltrated. They were fragmented by microtome, and observed under an optical microscope after Hematoxylin & Eosin staining. 8) A round acrylic cylinder with its upper side open was filled with clean water and depressive mouse models were forced to swim for 15 minutes. After 24 hours the animals were put in the same equipment for 5 minutes and were forced to swim. 9) The convenient, simple, and accurate high-performance liquid chromatography (HPLC) method was established for simultaneous determination of Neurotransmitters in MPTP-MYH group. Results 1) MYH possess Dopamine cell protective effect on MPTP-induced injury in striatum and substantia nigra pars compacta. 2) MYH inhibits the loss of tyrosine hydroxylase-immunoreacitive (TH-IR) cells in the striatum and substantia nigra pars compacta on MPTP-induced injury in C57BL/6 mice. 3) MYH possesses improvement effect on MPTP-induced memory deterioration in C57BL/6 mice through the reduction of prolongated Sort of lost time by MPTP injection using the Morris water maze test. 4) MYH possesses hippocampal neuron protective effect on MPTP-induced injury in C57BL/6 mice. 5) MYH possesses improvement effect on MPTP-induced motor behaviour deficits and depression in C57BL/6 mice through the reduction of prolongated losing motion by MPTP injection using the Forced swimming test. 6) MYH increases serotonin product amount on MPTP-induced injury in C57BL/6 mice. Conclusions This experiment suggests that the neuroprotective effect of MYH is mediated by the increase in Dopamin, TH-ir cell, Hippocampus and Serotonin. Furthermore, MYH essential oil may serve as a potential preventive or therapeutic agent regarding Parkinson's disease.