• The Korean Journal of Physiology and Pharmacology
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• v.20 no.2
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• pp.185-192
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• 2016

Ampicillin, a ${\beta}$-lactam antibiotic, dose-dependently protects neurons against ischemic brain injury. The present study was performed to investigate the neuroprotective mechanism of ampicillin in a mouse model of transient global forebrain ischemia. Male C57BL/6 mice were anesthetized with halothane and subjected to bilateral common carotid artery occlusion for 40 min. Before transient forebrain ischemia, ampicillin (200 mg/kg, intraperitoneally [i.p.]) or penicillin G (6,000 U/kg or 20,000 U/kg, i.p.) was administered daily for 5 days. The pretreatment with ampicillin but not with penicillin G significantly attenuated neuronal damage in the hippocampal CA1 subfield. Mechanistically, the increased activity of matrix metalloproteinases (MMPs) following forebrain ischemia was also attenuated by ampicillin treatment. In addition, the ampicillin treatment reversed increased immunoreactivities to glial fibrillary acidic protein and isolectin B4, markers of astrocytes and microglia, respectively. Furthermore, the ampicillin treatment significantly increased the level of glutamate transporter-1, and dihydrokainic acid (DHK, 10 mg/kg, i.p.), an inhibitor of glutamate transporter-1 (GLT-1), reversed the neuroprotective effect of ampicillin. Taken together, these data indicate that ampicillin provides neuroprotection against ischemia-reperfusion brain injury, possibly through inducing the GLT-1 protein and inhibiting the activity of MMP in the mouse hippocampus.

• Journal of Sasang Constitutional Medicine
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• v.26 no.2
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• pp.165-179
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• 2014

Objectives To evaluate the neuroprotective effects of Hyangsayangwi-tang (HY), a Korean traditional medicinal prescription in a Parkinson's disease mouse model. Methods Four groups(each of 10 mouse per group) were used in this study. The neuroprotective effect of HY was examined in a Parkinson's disease mouse model. C57BL/6 mouse treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30mg/kg/day), intraperitoneal (i.p.) for 5 days. Slow behavioral responses and memory disorder is the major clinical symptoms of PD. In order to investigate the effect of HY on recovery of behavioral deficits and memory, we examined the motor function and memory by using Morris water maze and Forced swimming test. Ischemic mouse brain stained with TTC(2,3,5 triphenyl tetrazolium chloride) in the MPTP-induced Parkinson's disease to find out ischemia and tissue damage in mouse. The convenient, simple, and accurate high-performance liquid chromatography (HPLC) method was established for simultaneous determination of neurotransmitters in MPTP-HY group. To measure the amount of dopamine in mice brain, striatum-substantia nigra, was examined by Bradford assay. Immunohistochemistry was examined in the MPTP-induced Parkinson's disease (PD) mouse to evaluate the neuroprotective effects of Hyangsayangwi-tang on hippocampal lesion, ST and SNpc. Results and Conclusions Hyangsayangwi-tang (HY) prevents MPTP-induced loss of serotonin, hippocampus and TH-ir cell.

• The Journal of Korean Medicine
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• v.23 no.4
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• pp.140-150
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• 2002

Objectives: The water extract of Omija-tang (OMIT) has traditionally been used for treatment of ischemic heart and brain damage in oriental medicine. However, little is known about the mechanism by which the water extract of OMJT rescues cells from these damages. Therefore, this study was designed to investigate the protective mechanisms of OMJT on oxidative stress-induced toxicity in H9c2 cardiomyoblast cells. Methods: Treatments of $H_2O_2$, or $ZnC_{12}$ markedly induced death of H9c2 cardiomyoblast cells in a dose-dependent manner. The characteristics of oxidative stress-induced death of H9c2 showed apparent apoptotic features such as DNA fragmentation. OMJT significantly reduced both ${H_2O_2}-induced$ cell death and chromatin fragmentation. The decrease of B치-XL expression by $H_2O_2$ were inhibited by OMJT. In addition, the increase of Bcl-XS expression was also inhibited by OMJT. In particular, Fas expression, which is generally recognized as cell death-inducing signal by Fas/FasL interaction, was markedly increased by H2O2 in a time-dependent manner. Also, the expression profile of proteins in Chang cells were screened by using two-dimensional (2-D) gel electrophoresis. Among 300 spots resolved in 2-D gels; the comparison of control versus apoptotis cells revealed that signal intensity of 6 spots decreased and 11 spots increased. Results and Conclusions: Taken together, this study suggests that the protective effects of the water extract of OMJT against oxidative damages may be mediated by the modulation of Bcl-XL/S Fas expression.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.4
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• pp.891-897
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• 2007

This experimental Study was designed to investigate the mechanism of Acanthopanacis Cortex Roots(ACR) 50% ethyl alcohol extract on the improvement of regional cerebral blood flow and cytokines production in cerebral ischemic rats. And was designed to investigate whether ACR inhibits lactate dehydrogenase(LDH) activity in neuronal cells The results were as follows; ACR significantly inhibited LDH activity in neuronal cells. These results suggest that ACR prevents the neuronal death. rCBF was significantly and stably increased by ACR(10 mg/kg, i.p.) during the period of cerebral reperfusion, which contrasted with the findings of rapid and marked increase in control group. In cytokine production of serum by drawing from femoral arterial blood at 1 hr after middle cerebral arterial occlusion, experimental group was significantly decreased $IL-1{\beta}$ and $TNF-{\alpha}$ production, and significantly increased IL-10 production compared with control group. In cytokine production of serum by drawing from femoral arterial blood at 1 hr after reperfusion, experimental group was significantly decreased $IL-1{\beta}$ and $TNF-{\alpha}$ production, and significantly increased IL-10 production compared with control group. According to above results, the author suggest that ACR had an anti-ischemic effect through the improvement of cerebral hemodynamics, and inhibitive effect on the brain damage by inhibited $IL-1{\beta}$ and $TNF-{\alpha}$ production, and accelerated IL-10 production.

• Journal of Korean Neurosurgical Society
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• v.29 no.10
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• pp.1289-1295
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• 2000

Purpose : Recent evidence suggests a possible role for leukocytes in brain injury following ischemia and reperfusion. This study examined the temporal profile of ischemic tissue damage and leukocyte response after transient middle cerebral artery occlusion(MCAO) with reperfusion in the mouse. Methods : Focal cerebral ischemia was made by temporary occluding of the stem of the proximal MCA. Two groups of the mouse were investigated : (1) sham operation(n＝10), and (2)those having the arterial occlusion released after 90 minute(n＝20). By 4 hours(n＝10) and 24 hours(n＝10) after the onset of ischemia-reperfusion, fluorescein videoimages were under-taken in the pial venules of the mouse using a closed cranial window technique. Rhodamine 6G was administered as a $80-100{\mu}l/min$ i.v. loading dose and a $30-40{\mu}l/min$ i.v. maintenance dose in saline to selectively label circulating leukocytes. Neuropathologic evaluation for brain injury was accomplished using the histochemical stain 2,3,5-triphen-yltetrazolium chloride(TTC) and hematoxylin and eosin(H & E) stain. Results : The mean number of adherent leukocytes to cerebral venules in the 90 minutes MCAO and 24 hours reperfusion group were $306{\pm}24$ compared with $72{\pm}8$ in the sham operation group. In the TTC staining method, the cortical infarct affecting 34.8% of hemispheric volume were created in all of animals (n＝10) undergoing 90 minute MCAO with 24 hours reperfusion, but the infarcted area were not found in the other(sham operation and 90 minute MCAO with 4 hours reperfusion)groups. In the H & E stain, the brain tissue following 90 minute MCAO with 4 hours reperfusion revealed only a pyknosis of the nuclei with shrunken cytoplasm, but infiltrated leukocytes were not observed. After 24 hours of reperfusion, a many leukocytes were infiltrated within parenchyma and blood vessles. Conclusions : These findings demonstrate the feasiblity of continous in vivo monitoring of leukocyte adherence in cerebral venules and suggest that reperfusion induced leukocyte adherence to venular endothelium may contribute to tissue injury following focal cerebral ischemia.

• Journal of Korean Neurosurgical Society
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• v.50 no.4
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• pp.370-376
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• 2011

Objective : Posttraumatic cerebral infarction (PTCI), an infarction in well-defined arterial distributions after head trauma, is a known complication in patients with severe head trauma. The primary aims of this study were to evaluate the clinical and radiographic characteristics of PTCI, and to assess the effect on outcome of decompressive hemicraniectomy (DHC) in patients with PTCI. Methods : We present a retrospective analysis of 20 patients with PTCI who were treated between January 2003 and August 2005. Twelve patients among them showed malignant PTCI, which is defined as PTCI including the territory of Middle Cerebral Artery (MCA). Medical records and radiologic imaging studies of patients were reviewed. Results : Infarction of posterior cerebral artery distribution was the most common site of PTCI. Fourteen patients underwent DHC an average of 16 hours after trauma. The overall mortality rate was 75%. Glasgow outcome scale (GOS) of survivors showed that one patient was remained in a persistent vegetative state, two patients were severely disabled and only two patients were moderately disabled at the time of discharge. Despite aggressive treatments, all patients with malignant PTCI had died. Malignant PTCI was the indicator of poor clinical outcome. Furthermore, Glasgow coma scale (GCS) at the admission was the most valuable prognostic factor. Significant correlation was observed between a GCS less than 5 on admission and high mortality (p<0.05). Conclusion : In patients who developed non-malignant PTCI and GCS higher than 5 after head injury, early DHC and duroplasty should be considered, before occurrence of irreversible ischemic brain damage. High mortality rate was observed in patients with malignant PTCI or PTCI with a GCS of 3-5 at the admission. A large prospective randomized controlled study will be required to justify for aggressive treatments including DHC and medical treatment in these patients.

• Journal of Chest Surgery
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• v.26 no.7
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• pp.513-520
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• 1993

Surgical treatment of aneurysm or dissection involving the ascending aorta and aortic arch still poses one of the most complicated technical and tactical challenges in surgery. The use of total circulatory arrest[TCA] with profound hypothermia in the surgical treatment of aneurysmal dissection involving the ascending aorta and aortic arch has been reported as popular surgical methods. However, the safe period of prolonged circulatory arrest with hypothermia remains controversial and ischemic damage to the central nervous system and uncontrollable perioperative bleeding have been the major problem. We have found profound hypothermic circulatory arrest with retrograde cerebral perfusion via the superior vena cava to achieve cerebral protection. We experiment the aortic anastomosis in 7 adult mongrel dogs, using profound hypothermic circulatory arrest with continuous retrograde cerebral perfusion[RGCP] via superior vena cava. We also studied the extent of cerebral protection using above surgical methods, by gas analysis of retrograde cerebral perfusion blood and returned blood of aortic arch, preoperative, intraoperative and postoperative electroencephalography and microscopic findings of brain tissue. The results were as follows: 1. The cooling time ranged from 15 minutes to 24 minutes[19.71$\pm$ 3.20 minutes] ; Aorta cross clamp time ranged from 70 minutes to 89 minutes[79.86 $\pm$ 7.54 minutes] ; Rewarming time ranged from 35 minutes to 47 minutes[42.86$\pm$ 4.30 minutes] ; The extracorporeal circulation time ranged from 118 minutes to 140 minutes[128.43$\pm$ 8.98 minutes] [Table 2]. 2. The oxygen content in the oxygenated blood after RGCP was 12.66$\pm$ 1.25 ml/dl. At 5 minutes after the initiation of RGCP, the oxygen content of returnedlood was 7.58$\pm$ 0.21 ml/dl, and at 15 minutes 7.35$\pm$ 0.17 ml/dl, at 30 minutes 7.20$\pm$ 0.19 ml/dl, at 60 minutes 6.63$\pm$ 0.14 ml/dl [Table 3]. 3. Intraoperative electroencephalographic finding revealed low amplitude potential during hypothermia, and no electrical impulse throughout the period of circulatory arrest and RGCP. Electrical activity appeared after reperfusion, and the electroencephalographic reading also recovered rapidly as body temperature returned to normal [Fig. 2]. 4. The microscopic finding of brain tissue showed widening of the interfibrillar spaces. But there was no evidence of tissue necrosis or hemorrhage [Fig. 3]. We concluded the retrograde cerebral perfusion during hypothermic circulatory arrest is a simplified technique that may have a excellent brain protection.

• The Journal of Korean Medicine
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• v.24 no.3
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• pp.51-64
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• 2003

Objective : This study investigated the alteration of neural activity and effect of Yanggyuksanhwa-tang (Lianggesanhuo-tang) on cerebral ischemia of rats. Methods : Considering age-related impact on cerebral ischemia, aged rats (18 months old) were used for this study. Ischemic damage was induced by the transient occlusion of bilateral common carotid arteries (BCAO) with hypotension. Yanggyuksanhwa-tang (Lianggesanhuo-tang) was administered twice a day orally. Then alterations of neural activities in the brain of aged BCAO rats were measured by the [$^{14}C$]2-deoxyglucose autoradiography method. Results : The BCAO in aged rats led to significant decrease of neural activity in the whole brain. Treatment with Yanggyuksanhwa-tang (Lianggesanhuo-tang) significantly attenuated the decrease of neural activity in the whole brain following BCAO ischemia. Treatment significantly attenuated the decrease of neural activity in the CA1, CA2, CA3, dentate gyrus of the hippocampus, activated barrel, barrel cortex, somatosensory cortex, cingulate cortex, caudate putamen, and medial septal nucleus following BCAO in aged rats. Treatment with Yanggyuksanhwa-tang (Lianggesanhuo-tang) also significantly attenuated the decrease of neural activity in the anteroventral thalamic nucleus, ventral anterior thalamic nucleus, arcuate nucleus, posterior hypothalamic area, medial mammillary nucleus, lateral periaqueductal gray, dorsal raphe nucleus, interpeduncular nucleus, median raphe nucleus, and medial pontine nucleus. Conclusion : It can be suggested that Yanggyuksanhwa-tang (Lianggesanhuo-tang) has a neuroprotecuve effect on cerebral ischemia through the control of glucose metabolic rate and cerebral blood flow.

• Clinical and Experimental Pediatrics
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• v.51 no.11
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• pp.1205-1210
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• 2008

Purpose : The development of the corpus callosum occupies the entire period of cerebral formation. The myelination pattern on magnetic resonance imaging (MRI) is very useful to evaluate neurologic development and to predict neurologic outcome in high risk infants. The thickness of the corpus callosum is believed to depend on the myelination process. It is possible to calculate the length and thickness of the corpus callosum on MRI. Thus, we can quantitatively evaluate the development of the corpus callosum. We investigated the clinical significance of measuring various portions of the corpus callosum in neonate with neurologic disorders such as hypoxic brain damage and seizure disorder. Methods : Forty-two neonates were evaluated by brain MRI. We measured the size of the genu, body, transitional zone, splenium, and length of the corpus callosum. Each measurement was divided by the total length of the corpus callosum to obtain its corrected size. The ratio of corpus callosal length and the anteroposterior diameter of the brain was also measured. Results : There was no statistical significance in the sample size of each part of the corpus callosum. However, the corrected size or the ratio of body of the corpus callosum correlated with periventricular leukomalacia and hypoxic ischemic encephalopathy. Conclusion : The abnormal size of the corpus callosum showed a good correlation with periventricular leukomalacia and hypoxic ischemic encephalopathy in neonates. We can predict clinical neurological problems by estimation of the corpus callosum in the neonatal period.

• The Journal of Internal Korean Medicine
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• v.23 no.2
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• pp.181-190
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• 2002

The water extract of Omija-tang(OMJT) has been traditionally used for treatment of ischemic heart and brain damage in oriental medicine. However, little is known about the mechanism by which the water extract of OMJT protects cells from such damage. Therefore, this study was conducted to investigate the protective mechanisms of OMJT on $H_2O_2$-induced toxicity in H9c2 cardiomyoblast cells. Treatment of $H_2O_2$ markedly induced death of H9c2 cardiomyoblast cells in a dose-dependent manner. The characteristics of $H_2O_2$-induced death of H9c2 showed apparent apoptotic features, such as DNA fragmentation. However, OMJT significantly reduced both $H_2O_2$-induced cell death and chromatin fragmentation. The decrease of Bcl-XL expression by $H_2O_2$ was inhibited by OMJT. In addition, the increase of Bcl-XS and Bax expression were also inhibited by OMJT. In particular, Fas expression, which is generally recognized as cell death inducing signal by Fas/FasL interaction, was markedly increased by $H_2O_2$ in a time-dependent manner, whereas this increase was completely prevented by OMJT. The combined treatment of OMJT and $H_2O_2$ in H9c2 cells also reduced activation of caspase-9 and caspase-3 like protease. Taken together, this study indicates that the protective effects of the water extract of OMJT against oxidative damage may be mediated by the modulation of BcI-XL/S and Bax expression by way of the regulation of mitochondrial membrane potential and caspase cascades.