• Nutrition Research and Practice
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• v.4 no.3
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• pp.196-202
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• 2010

To investigate the neuroprotective effects of bovine colostrums (BC), we evaluate the ability of consuming BC after focal brain ischemia/reperfusion injury rat model to reduce serum cytokine levels and infarct volume, and improve neurological outcome. Sprague-Dawley rats were randomly divided into 4 groups; one sham operation and three experimental groups. In the experimental groups, MCA occlusion (2 h) and subsequent reperfusion (O/R) were induced with regional cerebral blood flow monitoring. One hour after MCAO/R and once daily during the experiment, the experimental group received BC while the other groups received 0.9% saline or low fat milk (LFM) orally. Seven days later, serum pro-inflammatory cytokine (IL-$1{\beta}$, IL-6, and TNF-${\alpha}$) and anti-inflammatory cytokine (IL-10) levels were assessed. Also, the infarct volume was assessed by using a computerized image analysis system. Behavioral function was also assessed using a modified neurologic severity score and corner turn test during the experiment. Rats receiving BC after focal brain I/R showed a significant reduction (-26%/-22%) in infarct volume compared to LFM/saline rats, respectively (P < 0.05). Serum IL-$1{\beta}$, IL-6, and TNF-${\alpha}$ levels were decreased significantly in rats receiving BC compared to LFM/saline rats (P < 0.05). In behavioral tests, daily BC intake showed consistent and significant improvement of neurological deficits for 7 days after MCAO/R. BC ingestion after focal brain ischemia/reperfusion injury may prevent brain injury by reducing serum pro-inflammatory cytokine levels and brain infarct volume in a rat model.

• 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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.6
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• pp.1643-1651
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• 2004

This experimental study was designed to investigate the effects of SIEGESBECKIAE HERBA extract (SHE) on the change of cerebral hemodynamics 〔regional cerebral blood flow (rCBF) and mean arterial blood pressure(MABP)〕 in normal condition and cerebral ischemic rats, and to determine the mechanism of action of SHE. This study was designed to investigate whether or not SHE inhibit lactate dehydrogenase (LDH) activity in neuronal cells and cytokines production in serum of cerebral ischemic rats. The results were as follows SHE increased rCBF significantly in a dose-dependent manner, but MABP was not changed by SHE in normal rats. The SHE-induced increase in rCBF was significantly inhibited by pretreatment with indomethacin (IDN), an inhibitor of cyclooxygenase but was increased by methylene blue (MTB), an inhibitor of guanylate cyclase. SHE inhibited lactate dehydrogenase (LDH) activity significantly in neuronal cells. rCBF was increased significantly and stably by SHE(10㎎/㎏, i.p.) during the period of cerebral reperfusion, which contrasted with the findings of rapid and marked increase in control group in ischemic rats. In serum by drawing from femoral arterial blood after middle cerebral arterial occlusion(MCAO) for 1hr and reperfusion for 1hr, the sample group was decreased IL-1β production significantly compared to that of the control group. In serum by drawing from femoral arterial blood after MCAO 1hr and reperfusion 1hr, sample group decreased TNF-α production significantly compared to that of the control grolilp. In serum by drawing from femoral arterial blood after reperfusion 1hr, sample group increased TGF-β production significantly compared to that of the control group. In serum by drawing from femoral arterial blood after MCAO for 1hr and reperfusion for 1hr, IL-10 production of the sample group was similar to that of control group. These results suggested that SHE had inhibitive effect on the brain damage by inhibited LDH activity, IL-1β and TNF-α production, but accelerated TGF-β production.

• Korean Journal of Acupuncture
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• v.19 no.2
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• pp.63-78
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• 2002

Kupunggibodan(KU), Gamisamul-tang(GA) and Whangryunhaedok-tang(WH) are clinically the most popular prescriptions as an herbal medicine in the treatment of ischemia. In order to compare and evaluate their protective effects on the ischema-induced cognitive deficits by middle cerebral artery occlusion (MCAO), we examined its ability to improve ischemia-induced cell loss and impairements of learning and memory in the Morris water maze and eight-arm radial arm maze. Focal cerebral ischemia produced a marked cell loss, decrease in acetylcholinesterase(AchE) reactivity in the hippocampus, and learning and memory deficits in two behavioral tasks. Pretreatment with WH (100 mg/kg, p.o.) produced a substantial increase in acquisition in the Morris water maze. Pretreatment with KU increased the perfomance of the resention test in the Morris water maze. WH, KU and GA caused a significant improvement in choice accuracy in radial arm maze test. WH was superior to KU and GA in perfomance of the radial arm maze test. Consistent with behavioral data, staining with cresyl violet showed that pretreatments with WH, but not KU and GA significantly recovered the ischemia-induced cell loss in the hippcampal CA1 area. In addition, pretreatments with WH and KU recovered the ischemia-induced reduction of AchE reactivity in the hippocampal CA1 area. These results demonstrated that KU, GA and WH have protective effects against ischimea-induced learning and memory impairments and that the efficacy was the order of WH>KU>GA in tratment of ischemia induced memory deficits. The present studies provide an evidence of KU, GA and WH as putative treatment of vascular dementia. Supported by a fund from the Ministry of Health and Welfare(HMP-00-OO-04-0004), and the Brain Korea 21 Project from Korean Ministry of Education, Korea.

• The Journal of Korean Medicine
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• v.30 no.3
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• pp.70-78
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• 2009

Objectives : This study was aimed at examining the effects of the application of EA (electroacupuncture) at GV20 and LI4 in the early cerebral ischemia on the size of cerebral infarction, COX-2 and IL-6. Methods : For this experiment, 21, six-week-old male S-D (Sprague - Dawley) rats weighting 160g to 200g were selected and randomly classified into 3 groups, seven rats in each group. Brain ischemia was simulated using a modified Koizumi method which was performed on each rat. In the GV20 group, the GV20 of the SD rats was stimulated for thirty minutes with acupunctural electrode low frequency stimulator five hours after inducement of ischemia. For the LI4 group, the LI4 was stimulated as above, while for the Ischemia group, no stimulation was applied. Twenty-four hours after the experiment, stained cerebral tissues were examined and an immuno-histological test was done to examine inflammatory reaction Results : Out of the three groups, the LI4 group showed the smallest size of cerebral infarction and the Ischemia group showed the highest COX-2 (cyclooxygenase-2) expression value in the cortex of the cerebrum. In addition, the LI4 group showed the lowest COX-2 expression value in unknown putamen out of the three groups. Conclusions : We infer that EA, applied at LI4 and GV20 in early ischemia, is effective in delaying the expression of IL-6 (interleukin-6) and COX-2, the inflammatory agents manifested from stroke. In addition, application at LI4, rather than GV20, can lower the expression value of the inflammatory agents. Further, EA can be an effective way to block early inflammatory reaction in stroke.

• Proceedings of the Korean Society of Embryo Transfer Conference
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• 2002.11a
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• pp.111-111
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• 2002

Stroke occurs when local thrombosis, embolic particle or the rupture of blood vessele interrupts the blood floe to the brain. $\beta$-estradiol 17-valerate has been reported to exert neuroprotective effects when administered before an ischemic insult. Recently, the pathophysiology of cerebral ischemia has been studied extensively in rat with various methods. In the present study, we investigates whether $\beta$-estrodiol 17-valerate can protect against brain injury. RNA sample were extracted from the hippocampus of female rat, reverse-transcription in the presence of [$\alpha$32p] dATP. Differential gene express-ion profiles were revealed (Bone morphogenetic protein type 1A receptor, Protein disulphide isomerase, Leukemia inhibitor factor receptor, cytochrome bc- 1 complex-x core P, thiol-specific antioxidant protein). RT-PCR was used to validate the relative expression pattern obtained by the cDNA array. The precise relationship between the early expression of recovery genes and stroke is a matter of luther investigation. This Study was supported by the Korea Science and Engineering Foundation(KOSEF) through the Biohealth Products Research Center(BPRC), Inje University, Korea.

• Journal of Korean Neurosurgical Society
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• v.48 no.5
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• pp.391-398
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• 2010

Objective : This study was designed to validate the cell trafficking efficiency of the in vivo bioluminescence image (BLI) study in the setting of transplantation of the luciferase expressing bone marrow-derived mesenchymal stem cells (BMSC), which were delivered at each different time after transient middle cerebral artery occlusion (MCAO) in a mouse model. Methods : Transplanting donor BMSC were prepared by primary cell culture from transgenic mouse expressing luciferase (LUC). Transient focal infarcts were induced in 4-6-week-old male nude mice. The experiment mice were divided into five groups by the time of MSC transplantation : 1) sham-operation group, 2) 2-h group, 3) 1-day group, 4) 3-day group, and 5) 1-week group. BLI for detection of spatial distribution of transplanted MSC was performed by detecting emitted photons. Migration of the transplanted cells to the infarcted area was confirmed by histological examinations. Differences between groups were evaluated by paired t-test. Results : A focal spot of bioluminescence was observed at the injection site on the next day after transplantation by Signal intensity of bioluminescence. After 4 weeks, the mean signal intensities of 2-h, 1-day, 3-day, and 1-week group were $2.6{\times}10^7{\pm}7.4{\times}10^6$. $6.1{\times}10^6{\pm}1.2{\times}10^6$, $1.7{\times}10^6{\pm}4.4{\times}10^5$, and $8.9{\times}10^6{\pm}9.5{\times}10^5$, respectively. The 2-h group showed significantly higher signal intensity (p<0.01). The engrafted BMSC showed around the infarct border zones on immunohistochemical examination. The counts of LUC-positive cells revealed the highest number in the 2-h group, in agreement with the results of BLI experiments (p<0.01). Conclusion : In this study, the results suggested that the transplanted BMSC migrated to the infarct border zone in BLI study and the higher signal intensity of LUC-positive cells seen in 2 hrs after MSC transplantation in MCAO mouse model. In addition, noninvasive imaging in real time is an ideal method for tracking stem cell transplantation. This method can be widely applied to various research fields of cell transplantation therapy.

• Biomolecules & Therapeutics
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• v.25 no.3
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• pp.272-278
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• 2017

Fucoidan has been reported to exhibit various beneficial activities ranging from to antivirus and anticancer properties. However, little information is available about the effects of fucoidan on cerebral ischemia-reperfusion injury (IRI). Our study aimed to explore the effects of fucoidan on cerebral IRI, as well as the underlying mechanisms. Sprague-Dawley (SD) rats were randomly subjected to four groups: Sham, IRI+saline (IRI+S), IRI+80 mg/kg fucoidan (IRI+F80), and IRI+160 mg/kg fucoidan (IRI+F160). Fucoidan (80 mg/kg or 160 mg/kg) was intraperitoneally injected from 7 days before the rats were induced to cerebral IRI model with middle cerebral artery occlusion (MCAO) method. At 24 h after reperfusion, neurological deficits and the total infarct volume were determined. The levels of inflammation-associated cytokines (interleukin (IL)-$1{\beta}$, IL-6, myeloperoxidase (MPO), and tumor necrosis factor (TNF)-${\alpha}$), oxidative stress-related proteins (malondialdehyde (MDA) and superoxide dismutase (SOD)) in the ischemic brain were measured by enzyme-linked immunosorbent assay (ELISA). Besides, the levels of apoptosis-related proteins (p-53, Bax, and B-cell lymphoma (Bcl)-2) and mitogen-activated protein kinase (MAPK) pathway (phosphorylation-extracellular signal-regulated kinase (p-ERK), p-c-Jun N-terminal kinase (JNK), and p-p38) were measured. Results showed that administration of fucoidan significantly reduced the neurological deficits and infarct volume compared to the IRI+S group in a dose-dependent manner. Also, fucoidan statistically decreased the levels of inflammation-associated cytokines, and oxidative stress-related proteins, inhibited apoptosis, and suppressed the MAPK pathway. So, Fucoidan plays a protective role in cerebral IRI might be by inhibition of MAPK pathway.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2003.10a
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• pp.69-69
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• 2003

Neuroprotective strategies have been appeared to be effective in a variety of stroke models. One of the major focuses has been related to the activities of estrogen. $17\beta$-estradiol valerate(EV) has been reported to exert neuroprotective effects when administered before an ischemic insult. The purpose of this study was to determine whether EV can protect against brain injury via estrogen receptor. Chronic and acute pretreatment can reduce the ischemic damage of focal cerebral ischemia in OVX rat, indicating that EV may be a new therapeutic class of drugs to prevent neuronal damage associated with cerebral ischemia. RNAs were extracted from the hippocampus of ovariectomized female rat with or without EV. Differential gene expression profiles were revealed(Bone morphogenetic protein type 1A receptor, Protein disulphide isomerase, cytochrome bc-1 complex core P, thiol-specific antioxidant protein). RT-PCR and in situ hybridization were used to validate the relative expression pattern obtained by the cDNA array. This Study was supported by the Korea Science and Engineering Foundation(KOSEF) through the Biohealth Products Research Center(BPRC), Inje University, Korea

• Annals of Clinical Neurophysiology
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• v.16 no.2
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• pp.62-69
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• 2014

Background: Neuromodulation therapy has been used to an adjunctive treatment promoting motor recovery in stroke patients. The objective of the study was to determine the effect of repetitive transcranial magnetic stimulation (rTMS) on neurobehavioral recovery and evoked potentials in rats with middle cerebral artery occlusion. Methods: Seventy Sprague-Daley rats were induced permanent middle cerebral artery occlusion (MCAO) stroke model and successful stroke rats (n=56) assigned to the rTMS (n=28) and sham (n=28) group. The 10 Hz, high frequency rTMS gave on ipsilesional forepaw motor cortex during 2 weeks in rTMS group. The somatosensory evoked potential (SSEP) and motor evoked potential (MEP) were used to evaluate the electrophysiological changes. Behavioral function of the stroke rat was evaluated by the Rota rod and Garcia test. Results: Forty rats ($N_{rTMS}=20;\;N_{sham}=20$) completed all experimental course. The rTMS group showed better performance than sham group in Rota rod test and Garcia test at day 11 (p<0.05) but not day 18 (p>0.05). The amplitude of MEP and SSEP in rTMS group was larger than sham group at day 18 (p<0.05). Conclusions: These data confirm that the high frequency rTMS on ipsilesional cerebral motor cortex can help the early recovery of motor performance in permanent middle cerebral artery stroke model and it may simultaneously associate with changes in neurophysiological activity in brain.