• 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 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.

• Annals of Clinical Neurophysiology
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• v.4 no.1
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• pp.38-43
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• 2002

Background & Purpose : Dynamic susceptibility contrast MR imaging, one method of perfusion MRI, was developed to define cerebral hemodynamic status with good anatomical resolution. The authors investigated hemodynamic parameters using this imaging method, in an effort to identify hemodynamic changes on the remote crossed cerebellum of patients with a supratentorial infarct. Methods : Dynamic susceptibility contrast MR imaging was performed in 15 patients with only unilateral supratentorial infarcts. Imaging was obtained at the anatomic level of the cerebellum. rCBF, rCBV, MTT and TP were determined over both cerebellar hemispheres of interest. Results : The rCBF and rCBV values of the contralateral cerebellar hemisphere were significantly more decreased than those of the ipsilateral cerebellar hemisphere in 12 patients(p=0.028, 0.033). MTT and TP values of the contralateral and ipsilateral cerebellar hemispheres didn't reveal any differences(p=0.130, 0.121). Conclusions : The results of this work suggest that the region which are remote from the ischemic brain lesion shows no changes of MTT or TP but show decrease of rCBF and rCBV, mean to diaschisis, it also demonstrates that perfusion MRI is an easily available method to evaluate the hemodynamic status of the brain.

• Journal of Korean Neurosurgical Society
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• v.39 no.2
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• pp.130-135
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• 2006

Objective : After ischemic stroke, partial recovery of function frequently occurs and may depend on the plasticity of axonal connections. Here, we examine whether blockade of the Nogo/NogoReceptor[NgR] pathway might enhance axonal sprouting and thereby recovery after focal brain infarction. Methods : Adult male Sprague Dawley rats weighing $250{\sim}350g$ were used. Left middle cerebral artery occlusion[MCAO] was induced with a intraluminal filament. An osmotic mini pump [Alzet 2ML4, Alza Scientific Products, Palo Alto, CA] for the infusion of NgR-Ecto[310]-Fc to block Nogo/NgR pathway was implanted 1 week after cerebral ischemia. Prior to induction of ischemia, all animals received training in the staircase and rotarod test. Two weeks after biotin dextran amine injection, animals were perfused transcardially with PBS, followed by 4% paraformadehyde/PBS solution. Brain and cervical spinal cord were dissected. Eight coronal sections spaced at 1mm intervals throughout the forebrain of each animal with cresyl violet acetate for determination of infarction size. Images of each section were digitized and the infarct area per section was measured with image analysis software. Results : Histological examination at 11 weeks post-MCAO demonstrates reproducible stroke lesions and no significant difference in the size of the stroke between the NgR[310]Ecto-Fc protein treated group and the control group. Behavioral recovery is significantly better and more rapid in the NgR-Ecto[310]-Fe treated group. Blockade of NgR enhances axonal sprouting from the uninjured cerebral cortex and improves the return of motor task performance. Conclusion : Pharmacological interruption of NgR allows a greater degree of axonal plasticity in response this is associated with improved functional recovery of complicated motor tasks.

• Annals of Clinical Neurophysiology
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• v.14 no.2
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• pp.64-71
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• 2012

Background: It is generally accepted that upper motor neuron (UMN) lesion can alter lower motor neuron (LMN) function by the plasticity of neural circuit. However there have been only few researches regarding the axonal excitability of LMN after UMN injury especially during the acute stage. The aim of this study was to investigate the nerve excitability properties of the LMNs following an acute to subacute supratentorial corticospinal tract lesion. Methods: An automated nerve excitability test (NET) using the threshold tracking technique was utilized to measure multiple excitability indices in median motor axons of 15 stroke patients and 20 controls. Testing of both paretic and non-paretic side was repeated twice, during the acute stage and subacute stage. The protocols calculated the strength-duration time constant from the duration-charge curve, parameters of threshold electrotonus (TE), the current-threshold relationship from sequential sub-threshold current, and the recovery cycle from sequential supra-threshold stimulation. Results: On the paretic side, compared with the control group, significant decline of superexcitablity and increase in the relative refractory period were observed during the subacute stage of stroke. Additionally, despite the absence of statistical significance, a mildly collapsing in ('fanning in') of the TE was found. Conclusions: Our results suggest that supratentorial brain lesions can affect peripheral axonal excitability even during the early stage. The NET pattern probably suggests background membrane depolarization of LMNs. These features could be associated with trans-synaptic regulation of UMNs to LMNs as one of the "neural plasticity" mechanisms in acute brain injury.

• 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.

• Korean Journal of Acupuncture
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• v.35 no.4
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• pp.187-202
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• 2018

Objectives : Non-invasive transcranial electrical stimulation is one of therapeutic interventions to change in neural excitability of the cortex. Transcranial electro-acupuncture (TEA) can modulate brain functions through changes in cortical excitability as a model of non-invasive transcranial electrical stimulation. Some composites of fermented Scutellaria baicalenis (FSB) can activate intercellular signaling pathways for activation of brain-derived neurotrophic factor that is critical for formation of neural plasticity in stroke patients. This study was aimed at evaluation of combinatory treatment of TEA and FSB on behavior recovery and cortical neural excitability in rodent focal stroke model. Methods : Focal ischemic stroke was induced by photothrombotic injury to the motor cortex of adult rats. Application of TEA with 20 Hz and $200{\mu}A$ in combination with daily oral treatment of FBS was given to stroke animals for 3 weeks. Motor recovery was evaluated by rotating bean test and ladder working test. Electrical activity of cortical pyramidal neurons of stroke model was evaluated by using multi-channel extracellular recording technique and thallium autometallography. Results : Compared with control stroke group who did not receive any treatment, Combination of TEA and FSB treatment resulted in more rapid recovery of forelimb movement following focal stroke. This combination treatment also elicited increase in spontaneous firing rate of putative pyramidal neurons. Furthermore expression of metabolic marker for neural excitability was upregulated in peri-infract area under thallium autometallography. Conclusions : These results suggest that combination treatment of TEA and FSB can be a possible remedy for motor recovery in focal stroke.

• Journal of Preventive Medicine and Public Health
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• v.54 no.1
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• pp.55-62
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• 2021

Objectives: After heart disease, brain stroke (BS) is the second most common cause of death worldwide, underscoring the importance of understanding preventable and treatable risk factors for the outcomes of BS. This study aimed to model the survival of patients with BS in the presence of competing risks. Methods: This longitudinal study was conducted on 332 patients with a definitive diagnosis of BS. Demographic characteristics and risk factors were collected by a validated checklist. Patients' mortality status was investigated by telephone follow-up to identify deaths that may be have been caused by stroke or other factors (heart disease, diabetes, high cholesterol, etc.). Data were analyzed by the Lunn-McNeil approach at alpha=0.1. Results: Older age at diagnosis (59-68 years: adjusted hazard ratio [aHR], 2.19; 90% confidence interval [CI], 1.38 to 3.48; 69-75 years: aHR, 5.04; 90% CI, 3.25 to 7.80; ≥76 years: aHR, 5.30; 90% CI, 3.40 to 8.44), having heart disease (aHR, 1.65; 90% CI, 1.23 to 2.23), oral contraceptive pill use (women only) (aHR, 0.44; 90% CI, 0.24 to 0.78) and ischemic stroke (aHR, 0.52; 90% CI, 0.36 to 0.74) were directly related to death from BS. Older age at diagnosis (59-68 years: aHR, 21.42; 90% CI, 3.52 to 130.39; 75-69 years: aHR, 16.48; 90% CI, 2.75 to 98.69; ≥76 years: aHR, 26.03; 90% CI, 4.06 to 166.93) and rural residence (aHR, 2.30; 90% CI, 1.15 to 4.60) were directly related to death from other causes. Significant risk factors were found for both causes of death. Conclusions: BS-specific and non-BS-specific mortality had different risk factors. These findings could be utilized to prescribe optimal and specific treatment.

• The Korea Journal of Herbology
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• v.32 no.1
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• pp.25-31
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• 2017

Objectives : Mori Radicis Cortex (MRC), the root epidermis of Morus alba L., has been traditionally used to treat lung-related diseases in Korean Medicine. The common of MRC is Mulberry bark Morus bark, and it's pharmaceutical properties and taste are known as sweet and cold, and it promotes urination and reduce edema by reducing heat from the lungs and soothe asthma. In the present study, anti-apoptotic mechanism of MRC in middle cerebral artery occlusion (MCAO) model in mice. Methods : Two-hundred grams of MRC was extracted with methanol at room temperature for 5 days, and this was repeated one time. After filtration, the methanol was removed using vacuum evaporator, then stored at $-20^{\circ}C$ until use. C57BL/6 male mice were housed in an environment with controlled humidity, temperature, and light cycle. In order to determine beneficial effects of MRC on ischemia induced brain damage, infarct volume, neurological deficit scores, activities of several apoptosis-related proteins such as caspase-8, -9, Bcl-xL in MCAO-induced brains of mice were analyzed. Mice in MRC-treated groups were orally administered 30, 100, or 300 mg/kg of body weight for three consecutive days before commencing the MCAO procedure. Results : Pre-treatment of MRC significantly reduced infarct volume in MCAO subjected mice applied with 300 mg/kg of MRC methanol extract, and MRC effectively inhibited Bcl-xL reduction and caspase-9 activation caused by MCAO-induced brain damage. Conclusions : MRC showed neuro-protective effects by regulating apoptosis-related protein signals, and it can be a potential candidate for the therapy of ischemia-induced brain damage.

• Neonatal Medicine
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• v.18 no.1
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• pp.59-69
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• 2011

Purpose: Current studies have demonstrated the neuroprotective effects of 6-cyano-7-nitroquinoxalin-2,3-dione (CNQX) in many animal models of brain injury, including hypoxic-ischemic (HI) encephlopathy, trauma and excitotoxicity, but limited data are available for those during the neonatal periods. Here we investigated whether CNQX can protect the developing rat brain from HI injury via mediation of nitric oxide synthase. Methods: In an in vivo model, left carotid artery ligation was done in 7-day-old Sprague-Dawley (SD) rat pups. The animals were divided into six groups; normoxia (N), hypoxia (H), hypoxia with sham-operation (HS), hypoxia with operation (HO), HO treated with vehicle (HV), and HO treated with CNQX at a dose of 10 mg/kg (HC). Hypoxia was made by exposure to a 2 hr period in the hypoxic chamber (92% $N_2$, 8% $O_2$). In an in vitro model, embryonic cortical neuronal cell culture of SD rats at 18-day gestation was done. The cultured cells were divided into three groups: normoxia (N), hypoxia (H), and hypoxia treated with CNQX (HC). The N group was prepared in 5% $CO_2$ incubators and the other groups were placed in 1% $O_2$) incubators (94% $N_2$, 5% $CO_2$) for 16 hr. Results: In the in vitvo and in vivo models, the expressions of iNOS and eNOS were reduced in the hypoxia group when compared to the normoxia group, whereas they were increased in the CNQX-treated group compared to the hypoxia group. In contrast, the expression of nNOS was showed reversely. Conclusion: CNQX has neuroprotective property over perinatal HI brain injury via mediation of nitric oxide synthase.