• Radiation Oncology Journal
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• v.16 no.2
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• pp.125-138
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• 1998

Purpose : To evaluate the late effect(3 and 6 months) of cis-diarnrninedichlo-roplatinum(II)(cisplatin) on the radiation brain damage when the cisplatin was intraperitoneally infused immediately after whole brain irradiation in the rats. Materials and Methods : The histolopathological findings of the brain were examined in rat brains at 3 and 6 months after the treatment. The rats were irradiated(20 or 22.5 Gy, RT) or cisplatin was injected intraperitoneally(2,4, or 8mg/kg, CT) and in combined treatment group, cisplatin(2mg/kg) was injected immediately after irradiation(20 or 22.5 Gr). Histopathological examination was done mostly in irradiation or cisplatin alone groups, because the rats in combined group died during experimental period except 2 rats. Results : The rats treated with cisplatin showed marked epithelial vacuolation with perivascular edema and vascular dilatation in choroid plexus at 3 months as well as multifocal necrosis involving fimbria and cerebellar hemispheres at 3 and 6 months. The changes were more prominent in rats with 2mg/kg injection compared to rats with 8mg/kg injection. The rats with RT and combined CT and RT showed characteristic delayed irradiation effects such as focal coagulation necrosis and vascular changes, which were more marked than previous reports Prominent perivascular and leptomenin-geal astrocytic Proliferation was well documented by anti-GFAP antibody. Cisplatin treatment did not enhance the effect of radiation-induced changes of blood vessels and astrocytic proliferation. Conclusion : The focal necrosis was the most consistently noted finding in this study, it suggested the possibility to use this as an evaluation factor for combined effects of RT and cisplatin.

• Journal of Pharmacopuncture
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• v.14 no.3
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• pp.5-17
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• 2011

Objectives : Gliosis becomes physical and mechanical barrier to axonal regeneration. Reactive gliosis induced by middle cerebral artery occlusion is involved with up-regulation of CD81 and GFAP (Glial fibrillary acidic protein). The current study is to examine the effect of the Angelica gigas Nakai(intravenous injection. 100 mg/kg twice in a day) on CD81 and GFAP of the rat in the brain after middle cerebral artery occlusion. Methods : Cerebral infarction was induced by middle cerebral artery occlusion. And after intravenous injection of water extract of Angelica gigas Nakai, the size of cerebral infarction was measured. Examination of optical microscope were also used to detect the expression of CD81 and GFAP in the brain of the rat. Results : The following results were obtained : We found that size of cerebral infarcion induced by MCAO (Middle Cerebral Artery Occlusion) in rats were decreased after intravenous injection of Angelica gigas Nakai. We injected the extract of Angelica gigas Nakai to the MCAO in rats, and the optical microscope study showed that Angelica gigas Nakai had effect on protecting the cells of hippocampus. We found that GFAP, CD81 and ERK of the brain in rats with cerebral infarction after MCAO were meaningfully decreased after intravenous injecting Angelica gigas Nakai. We found that c-Fos expression of the brain in rats with cerebral infarction after MCAO were significantly increased after intravenous injecting Angelica gigas Nakai. Conclusions : These results indicate that Angelica gigas Nakai could suppress the reactive gliosis, which disturbs the astrocyte regeneration in the brain of the rat with cerebral infarction after MCAO by controlling the expression of CD81 and GFAP. And the effect may be modulated by the up-regulation of c-Fos and ERK.

• The Journal of Korean Medicine
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• v.19 no.1
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• pp.392-409
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• 1998

The present experiment was designed to examine the effects of Jeongjihwan on carecholamines, serotonin, amino acids, lipid peroxide, free radical scavenging activity, malondialdehyde and superoxide dismutase activity in senile brain. It was performed by administering Jeongjihwan extracts of a variety of concentration to senile rats to experimentally determine effects of Jeongjihwan on biochemical changes in senile brain and examine protective effects against neurotoxin. To examine survival rate, the rat's spinal cord sensory ganglion cell pretreated in Jeongjihwan extracts was cultured in oxygen free radical. The results were summarized as follows: 1. Jeongjihwan significantly increased noradrenaline in the hippocampus and hypothalamus of the brain tissue of senile rats, and even though Jeongjihwan increased noradrenaline also in other brain tissue, there was no significance. 2. Jeongjihwan had no effects on dopamine changes in all brain tissue of senile rats. 3. Jeongjihwan significantly increased serotonin, but decreased in other brain tissue. 4. Jeongjihwan increased amino acid in the brain tissue of senile rats. 5. Jeongjihwan significantly decreased lipid peroxide and free radical in the brain tissue of senile rats. 6. Jeongjihwan significantly increased survival rate of nerve cell exposed to oxygen free radical. According to the above results, Jeongjihwan is assumed to improve brain function by reacting on biochemical changes of the senile brain and carries effects of protecting against neurocytotoxicity, and that Jeongjihwan can be used to treat regressive brain disease carrying symptoms of psychoactive disorders.

• Journal of Korean Neurosurgical Society
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• v.38 no.4
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• pp.287-292
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• 2005

Objective : Kainic acid[KA] enhances the expression of nitric oxide synthase, increases nitric oxide[NO], and thus evokes epileptic convulsion, which results in neuronal damage in the rat brain. NO may stimulate cyclooxygenase type-2 [COX-2] activity, thus producing seizure and neuronal injury, but it has also been reported that KA-induced seizure and neurodegeneration are aggravated on decreasing the COX-2 level. This study was undertaken to investigate whether the suppression of NO using the NOS inhibitor, N-nitro-L-arginine methyl ester[L-NAME], suppresses or enhances the activity of COX-2. Methods : Silver impregnation and COX-2 immunohistochemical staining were used to localize related pathophysiological processes in the rat forebrain following KA-induced epileptic convulsion and L-NAME pretreatment. Post-injection survival of the rat was 1, 2, 3days and 2months, respectively. Results : After the systemic administration of KA in rats, neurodegeneration increased with time in the cornu ammonis [CA] 3, CA 1 and amygdala, as confirmed by silver impregnation. On pretreating L-NAME, KA-induced neuronal degeneration decreased. COX-2 enzyme activities increased after KA injection in the dentate gyrus, CA 3, CA 1, amygdala and pyriform cortex, as determined by COX-2 staining. L-NAME pretreatment prior to KA-injection, caused COX-2 activities to increase compared with KA- injection only group by 1day and 2days survival time point. Conclusion : These results suggest that L-NAME has a neuroprotective effect on KA-induced neuronal damage, especially during the early stage of neurodegeneration.

• Journal of Ginseng Research
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• v.31 no.1
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• pp.44-50
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• 2007

Ginseng powerfully tonifies the original Qi. Ginseng used for insomnia, palpitations with anxiety, restlessness from deficient Qi and blood and mental disorientation. In order to investigate whether Ginseng cerebral ischemia-induced neuronal and cognitive impairments, we examined the effect of Ginseng on ischemia-induced cell death in the hippocampus, and on the impaired learning and memory in the Morris water maze and passive avoidance in rats. Ginseng when administered to rat at a dose of 200 mg/kg i.p. water extracts to 0 minutes and 90 minutes after 4-VO, significantly neuroprotective effects by 86.4% in the hippocampus of treated rats. For behavior test, rats were administered Ginseng (200mg/kg p.o.) daily for two weeks, followed by their training to the tasks. Treatment with Ginseng produced a marked improvement in escape latency to find the platform in the Morris water maze. Ginseng reduced the ischemia-induced learning disability in the passive avoidance. Consistent with behavioral data, treatments with Ginseng reduced jschemia-induced cell death in the hippocampal CA1 area. Oxidative stress is a causal factor in the neuropathogenesis of ischemic-reperfusion injury. Oxidative stress was examined in a rat model of global brain ischemia. The effects of Ginseng on lipid peroxidation (inhibition of the production of malondialdehyde, MDA) in different regions of the rat brain were studied. Ferrous sulfate and ascorbic acid (FeAs) were used to induce lipid peroxidation. The antiperoxidative effect showed 48-72% protection from tissue damage as compared with untreated animals. These results showed that Ginseng have a protective effect against ischemia-induced neuronal loss and learning and memory damage.

• Molecules and Cells
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• v.20 no.2
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• pp.189-195
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• 2005

Ethanol has long been implicated in triggering apoptotic neurodegeneration. We examined the effects of ethanol on the rat brain during synaptogenesis when a spurt in brain growth occurs. This period corresponds to the first 2 postnatal weeks in rats and is very sensitive to ethanol exposure. Ethanol was administered subcutaneously to 7-day- postnatal rat pups by a dosing regimen of 3 g/kg at 0 h and again at 2 h. Blood ethanol levels peaked ($677{\pm}16.4mg/dl$) at 4 h after the first ethanol administration. The cerebral cortexes of the ethanol-treated group showed several typical symptoms of apoptosis such as chromosome condensation and disintegration of cell bodies. Activated caspase-3 positive cells were found in the cortex within 2 h of the first injection, and reached a peak at 12 h. In addition, TUNEL staining revealed DNA fragmentation in the same regions. These results demonstrate that acute ethanol administration causes neuronal cell death via a caspase-3-dependent pathway within 24 h, suggesting that activation of caspase-3 is a marker of the developmental neurotoxicity of ethanol.

• Journal of Ginseng Research
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• v.37 no.4
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• pp.401-412
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• 2013

Korean Red Ginseng (KRG) is an oriental herbal preparation obtained from Panax ginseng Meyer (Araliaceae). To expand our understanding of the action of KRG on central nervous system (CNS) function, we examined the effects of KRG on tissue plasminogen activator (tPA)/plasminogen activator inhibitor-1 (PAI-1) expression in rat primary astrocytes. KRG extract was treated in cultured rat primary astrocytes and neuron in a concentration range of 0.1 to 1.0 mg/mL and the expression of functional tPA/PAI-1 was examined by casein zymography, Western blot and reverse transcription-polymerase chain reaction. KRG extracts increased PAI-1 expression in rat primary astrocytes in a concentration dependent manner (0.1 to 1.0 mg/mL) without affecting the expression of tPA itself. Treatment of 1.0 mg/mL KRG increased PAI-1 protein expression in rat primary astrocytes to $319.3{\pm}65.9%$ as compared with control. The increased PAI-1 expression mediated the overall decrease in tPA activity in rat primary astrocytes. Due to the lack of PAI-1 expression in neuron, KRG did not affect tPA activity in neuron. KRG treatment induced a concentration dependent activation of PI3K, p38, ERK1/2, and JNK in rat primary astrocytes and treatment of PI3K or MAPK inhibitors such as LY294002, U0126, SB203580, and SP600125 (10 ${\mu}M$ each), significantly inhibited 1.0 mg/mL KRG-induced expression of PAI-1 and down-regulation of tPA activity in rat primary astrocytes. Furthermore, compound K but not other ginsenosides such as Rb1 and Rg1 induced PAI-1 expression. KRG-induced up-regulation of PAI-1 in astrocytes may play important role in the regulation of overall tPA activity in brain, which might underlie some of the beneficial effects of KRG on CNS such as neuroprotection in ischemia and brain damaging condition as well as prevention or recovery from addiction.

• Korean Journal of Biological Psychiatry
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• v.3 no.2
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• pp.181-190
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• 1996

To clarify the mechanism of action of electroconvulsive shack(ECS) in respect to molecular biology, and to detect the quantitative amount of change of c-fos gene expression after ECS in the rat's brain, the authors obtained brain specimens from the striatum, cerebral cortex, hippocampus, and cerebellum. Each brain was removed within 30min. after ECS(130V, 0.5sec) and ECS-sham. Then we performed RT-PCR. The results are 1) ECS was found to affect the expression of immediate early genes. 2) the cerebral cortex and hippocampus was more influenced by ECS thon in the cerebellum and striatum. From these results, we can suggest that ECS is related to the mechanism of cognition, mood, memory which is correlated to cerebral cortex and hippocampus.

• The Journal of Korean Medicine
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• v.29 no.2
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• pp.47-59
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• 2008

Object: Reactive gliosis that is induced by central nervous system (CNS) injury is involved with up-regulation of CD81 and GFAP. The present study was to examine the effect of the Salvia miltiorrhiza on CD81 and GFAP regulation following brain injury. Methods: Immunoblot and ELISA methods were used to define the level of CD81 and GFAP in the astrocyte cultured from rat brain. Then immunohistochemistry was used to detect CD81 and GFAP in the injured rat brain. Results: The following results were obtained. 1. We did western blot and ELISA to detect the protein isolated from the whole cell and they showed that CD81 and GFAP decreased. 2. We injected Salvia miltiorrhiza extract intravenously to brain-injured rats for 7 days and 30 days, and the immunohistochemistry analyses showed that CD81 and GFAP decreased significantly. Conclusion: These results indicate that Salvia miltiorrhiza could suppress the reactive gliosis, which disturbs the neural regeneration following CNS injury, by controlling the expression of CD81 and GFAP.

• Journal of Korean Neurosurgical Society
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• v.63 no.2
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• pp.163-170
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• 2020

Objective : Milk fat globule-epidermal growth factor VIII (MFG-E8) may play a key role in inflammatory responses and has the potential to function as a neuroprotective agent for ameliorating brain injury in cerebral infarction. This study aimed to determine the role of MFG-E8 in brain injury in the subacute phase of cerebral ischemia in a rat model. Methods : Focal cerebral ischemia was induced in rats by occluding the middle cerebral artery with the modified intraluminal filament technique. Twenty-four hours after ischemia induction, rats were randomly assigned to two groups and treated with either recombinant human MFG-E8 or saline. Functional outcomes were assessed using the modified Neurological Severity Score (mNSS), and infarct volumes were evaluated using histology. Anti-inflammation, angiogenesis, and neurogenesis were assessed using immunohistochemistry with antibodies against ionized calcium-binding adapter molecule 1 (Iba-1), rat endothelial cell antigen-1 (RECA-1), and bromodeoxyuridine (BrdU)/doublecortin (DCX), respectively. Results : Our results showed that intravenous MFG-E8 treatment did not reduce the infarct volume; however, the mNSS test revealed that neurobehavioral deficits were significantly improved in the MFG-E8-treated group than in the vehicle group. Immunofluorescence staining revealed a significantly lower number of Iba-1-positive cells and higher number of RECA-1 in the periinfarcted brain region, and significantly higher numbers of BrdU- and DCX-positive cells in the subventricular zone in the MFG-E8-treated group than in the vehicle group. Conclusion : Our findings suggest that MFG-E8 improves neurological function by suppressing inflammation and enhancing angiogenesis and neuronal proliferation in the subacute phase of cerebral infarction.