• The Korean Journal of Pharmacology
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• v.30 no.3
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• pp.273-289
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• 1994

Reversible brain ischemia was produced by occluding both common carotid arteries for 5 min, and the effects of aminoguanidine (AG), $DL-{\alpha}-difluoromethylornithine$ (DFMO), MK-801, and nimodipine (NM) on the ischemia induced changes of the polyamine, glutamate and acetylcholine levels in the hippocampus CA1 subfield and the specific $[^3H]\;MK-801$ binding to the hippocampus synaptosomal membranes were studied with a histological reference of the cresyl violet stained hippocampus. The basal putrescine level $(PT:\;74.4{\pm}8.8\;nM)$ showed a rapid increase (up to 1.7 fold) for 5 min of ischemia, remained significantly increased for 6 h, and then resumed the further increase to amount gradually up to about 3 fold 96 h after recirculation. However, the level of spermidine was little changed, and the spermine level showed a transient increase during ischemia followed by a sustained decrease to about 40% of the preischemic level after recirculation. The increase of PT level induced by brain ischemia was enhanced with AG or MK-801, but it was reduced by DFMO or NM. The basal glutamate level $(GT:\;0.90{\pm}0.l4\;{\mu}M)$ rapidly increased to a peak level of $8.19{\pm}1.14\;{\mu}M$ within 5 min after onset of the ischemia and then decreased to the preischemic level in about 25 min after recirculation. And NM reduced the ischemia induced increase of GT level by about 25%, but AG, DFMO and MK-801 did not affect the GT increase. The basal acetylcholine level $(ACh:\;118.0{\pm}10.5\;{\mu}M)$ did little change during/after brain ischemia and was little affected by AG or NM. But DFMO and MK-801, respectively, produced the moderate decrease of ACh level. The specific $[^3H]\;MK-801$ binding to the hippocampus synaptosomal membrane was little affected by brain ischemia for 5 min. The control value (78.9 fmole/mg protein) was moderately decreased by AG and MK-801, respectively but was little changed by DFMO or NM. The microscopic findings of the brains extirpated on day 7 after ischemia showed severe neuronal damage of the hippocampus, particularly CA1 subfield. NM and AG moderately attenuated the delayed neuronal damage, and DFMO, on the contrary, aggravated the ischemia induced damage. However, MK-801 did not protect the hippocampus from ischemic damage. These results suggest that unlike to the mode of anti-ischemic action of NM, AG might protect the hippocampus from ischemic injury as being negatively regulatory on the N-methyl-D-aspartate (NMDA) receptor function in the hippocampus.

• Neonatal Medicine
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• v.15 no.1
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• pp.32-37
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• 2008

Purpose : Perinatal asphyxia is an important cause of neonatal mortality and subsequent lifelong neurodevelopmental handicaps. Although many treatment strategies have been tested, there is currently no clinically effective treatment to prevent or reduce the harmful effects of hypoxia and ischemia in humans. In the clinical setting, maternal hyperthermia induces adverse effects on the neonatal brain, but recent studies have shown that hyperthermic pretreatment (PT) plays some role in hypoxic-ischemic (HI) injuries of the developing brain. The present study investigated the effect of hyperthermic PT on HI brain injuries in newborn rats. Methods : HI was produced in 7-day-old neonatal rats by unilateral common carotid artery ligation, followed by hypoxia with 8% oxygen at $38^{\circ}C$ for 2 hours. Twenty-four hours before HI, one-half of the pups were exposed to a $40^{\circ}C$ environment for 2 hours. The severity of the brain injury was assessed 7 days after the HI. Results : Hyperthermic PT reduced the gross and histopathologic findings of brain injury from 64.7 to 31.2% (P<0.05). There were no differences in location and severity of injury between the pretreated and control brains. Conclusion : These findings indicate that hyperthermic PT provides neuroprotective benefits on HI in the developing brain. Also, these findings suggest maternal hyperthermia may have protective effect on perinatal HI brain injuries.

• Journal of Life Science
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• v.29 no.11
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• pp.1258-1266
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• 2019

Yangkyuksanhwa-Tang (YKSH), consisting of nine different herbs, is commonly used in Soyangin-type individuals with stroke, based on the Sasang Constitution Theory in Korea. However, no evidence has yet confirmed a beneficial effect of YKSH in ischemic stroke treatment. In this study, we investigated the effects of YKSH on ischemic brain injury in a mouse model of cerebral ischemia. Focal cerebral ischemia in mice was induced by photothrombosis, and behavioral recovery was evaluated. Infarct volume, inflammation, and newly generated cells were evaluated by histology and immunochemistry. YKSH treatment resulted in a significant recovery from the motor impairments induced by focal cerebral ischemia, as determined with wire grip and rotarod tests. YKSH treatment also decreased the infarct volume and the number of cells positive for tumor necrosis factor-${\alpha}$ and myeloperoxidase when compared with a vehicle-treated control group. By contrast, YKSH treatment considerably increased the number of cells positive for glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1, as well as the number of cells doubly positive for Ki67/doublecortin when compared with the vehicle-treated group. These results suggest that YKSH treatment attenuated the infarct size by anti-inflammatory action, astrocyte and microglia activation, and neuronal proliferation, thereby facilitating neurofunctional recovery from a cerebral ischemic assault. YKSH could therefore be a potential treatment for neurofunctional restoration of the injured brains of patients with stroke.

• Investigative Magnetic Resonance Imaging
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• v.6 no.1
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• pp.55-63
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• 2002

Purpose : We investigated the predictive values of relative CBV measured with perfusion MR imaging, and relative CBF measured with SPECT for tissue outcome in acute ischemic stroke. Material and Methods : Thirteen patients, who had acute unilateral middle cerebral artery occlusion, underwent perfusion MR imaging, and $^{99m}Tc-HMPAO$ SPECT within 6 hours after the onset of symptoms. Lesion-to-contralateral ratios of perfusion parameters were measured, and best cut-off values of both parameter ratios with their accuracy to discriminate between regions with and without evolving infarction were calculated. Results : Mean relative CBV ratios in regions with evolving infarction and without evolving infarction were $0.58{\pm}0.27$ and $0.9{\pm}0.17$ (p < 0.001), and mean relative CBF ratios in those regions were $0.41{\pm}0.22$ and $0.71{\pm}0.14$ (p < 0.001). The best cutoff values to discriminate between regions with and without evolving infarction were estimated to be 0.80 for relative CBV ratio and 0.56 for relative CBF ratio. The sensitivity, specificity and efficiency of each cutoff value were 80.6, 87.5, 82.7% for relative CBV ratio, and 72.2, 75.0, 73.0% for relative CBF ratio (p > 0.05 between two parameters). Conclusion Measurement of relative CBV and relative CBE may be useful in predicting tissue outcome in acute ischemic stroke.

• Clinical and Experimental Pediatrics
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• v.49 no.2
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• pp.198-202
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• 2006

Purpose : Fas is a cell surface receptor that transduces apoptotic death signals. Interaction of extracelluar domain of Fas with Fas ligand(FasL) triggers the apoptotic process in many diseases. We investigated the expression of Fas and FasL in the hippocampus of 7-day-old newborn rat brains following hypoxia-ischemia injury. Methods : The 7-days-old newborn rats were exposed to 8 percent oxygen for two hours after the ligation of right common carotid arteries. The newborn rats were killed and their brains were removed at 12, 14 and 48 hours after hypoxic-ischemic injury. The expressions of Fas and FasL of the right hippocampus were observed by western blotting and immunofluorescent staining. Results : Fas and FasL were strongly expressed in the right hippocampus ipsilateral to the ligation of the common carotid artery by western blotting at 12 hours following hypoxic-ischemic injury, and then slowly decreased. The immunofluorescent expressions of Fas and FasL strongly increased in the CA1 area of the right hippocampus at 12 and 24 hours following hypoxic-ischemic injury. The immunofluorescent expression of Fas decreased at 48 hours, but the expression of FasL persisted strongly at 48 hours following hypoxic-ischemic injury. Conclusion : The interaction of Fas with FasL on the cell surface may be involved in neuronal injury following hypoxic-ischemic injury in the developing brain.

• Clinical and Experimental Pediatrics
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• v.46 no.10
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• pp.989-995
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• 2003

Purpose : Dexamethasone is frequently administered to prevent or treat chronic lung disease in human neonates who are also prone to hypoxic-ischemic(HI) insults. Recently, meta-analysis of the follow-up studies reveals a significantly increased odd ratio for the occurrence of cerebral palsy or an abnormal neurologic outcome, and there is conflicting evidence regarding the impact of dexamethasone exposure on HI brain injury. This study was conducted to explore the effect of post-HI dexamethasone administration on neuronal injury in neonatal rats. Methods : HI was produced in seven-day-old rats by right carotid artery ligation followed by two hours of 8% oxygen exposure. At the end of HI, the animals were injected intraperitoneally either with dexamethasone(0.5 mg/kg) or saline. Neuronal injury was assessed seven days after the HI by the area of infarction, TUNEL reactivity, Bcl-2 and Bax expression in brain. Results : Post-insult dexamethasone administration resulted in reduction of weight gain and a higher mortality rate during seven days after HI. Dexamethasone treatment revealed no effect on the size of brain infarction induced by HI. Bax protein expression increased in dexamethasone treated brain but Bcl-2 protein expression and TUNEL reactivity revealed no significant differences between dexamethasone treated and non treated brain. Increased Bax protein expression suggest upregulation of the apoptosis by dexamethasone. Conclusion : The result suggests the adverse role of Post-HI administration of dexamethasone in neonatal HI.

• Journal of Industrial Convergence
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• v.17 no.4
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• pp.39-43
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• 2019

Mouse embryonic stem cell could show an substitutional materials of cells of neuron differentiation, positively increasing their effectiveness in the treatment of nervous symptom. We examined that mouse embryonic stem cells (mESCs) can be induced to undergo neuronal differentiation. After neuronal induction, the phenotype of mESCs changed towards neuronal morphology and mESCs were injected into the lateral ventricle of the experimental animal brain. Transplanted cells migrated to various parts of the brain and ischemic brain injury by middle cerebral artery occlusion (MCAO) increased their migration to the injured cortex. Intracerebral grafting of mESCs mostly improve sensory and motor nervous system of neurological injury in focal cerebral rats.

• 대한핵의학회:학술대회논문집
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• 1991.05a
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• pp.151.2-151.2
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• 1991

• The Journal of the Korea Contents Association
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• v.11 no.2
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• pp.341-352
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• 2011

The purpose of this study was carried out to investigate the effect of electroacupuncture on reactive gliosis expressing GFAP in rat with transient global cerebral ischemia. Subjects were randomly divided into two groups, a control group and a electroacupuncture group on ST36, LI11 and SP9 with 2 Hz and 1 mA. The rats were sacrificed on 1, 3 and 7 days after transient cerebral ischemia using ligation of left common carotid artery. After making brain slide sections, they were immunostained with GFAP antisera(1:2,500). The results were as follows: The numbers of astrocytes of electroacupuncture group were decreased than those of control group at every 1, 2 and 7 days. Especially, the numbers of astrocytes at 3 days(p<0.01) and 8 days(p<0.05) were different statistically. And astrocytes had resting, hypertrophic and moving types on cerebral cortex. The decrease of numbers of astrocytes expressing GFAP showed that electroacupuncture could localise and minimize the brain damage by transient cerebral ischemia and cause brain cell plasticity.

• Clinical and Experimental Pediatrics
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• v.52 no.5
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• pp.594-602
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• 2009

Purpose : Transforming growth factor (TGF)-${\beta}1$ reportedly increases neuronal survival by inhibiting the induction of inducible nitric oxide synthase (NOS) in astrocytes and protecting neurons after excitotoxic injury. However, the neuroprotective mechanism of $TGF-{\beta}1$ on hypoxic-ischemic (HI) brain injury in neonatal rats is not clear. The aim of this study was to determine whether $TGF-{\beta}1$ has neuroprotective effects via a NO-mediated mechanism and N-methyl-D-aspartate (NMDA) receptor modulation on perinatal HI brain injury. Methods : Cortical cells were cultured using 19-day-pregnant Sprague-Dawley (SD) rats treated with $TGF-{\beta}1$ (1, 5, or 10 ng/mL) and incubated in a 1% O2 incubator for hypoxia. Seven-day-old SD rat pups were subjected to left carotid occlusion followed by 2 h of hypoxic exposure (7.5% $O_2$). $TGF-{\beta}1$ (0.5 ng/kg) was administered intracerebrally to the rats 30 min before HI brain injury. The expressions of NOS and NMDA receptors were measured. Results : In the in vitro model, the expressions of endothelial NOS (eNOS) and neuronal NOS (nNOS) increased in the hypoxic group and decreased in the 1 ng/mL $TGF-{\beta}1-treated$ group. In the in vivo model, the expression of inducible NOS (iNOS) decreased in the hypoxia group and increased in the $TGF-{\beta}1$-treated group. The expressions of eNOS and nNOS were reversed compared with the expression of iNOS. The expressions of all NMDA receptor subunits decreased in hypoxia group and increased in the $TGF-{\beta}1$-treated group except NR2C. Conclusion : The administration of $TGF-{\beta}1$ could significantly protect against perinatal HI brain injury via some parts of the NO-mediated or excitotoxic mechanism.