• Neonatal Medicine
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• v.17 no.2
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• pp.181-192
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• 2010

Purpose: Current studies have demonstrated the neuroprotective effects of dizocilpine (MK-801) 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 dizocilpine can protect the developing rat brain from HI injury via anti-apoptosis. Methods: In an in vitro model, embryonic cortical neuronal cell culture of Sprague-Dawley (SD) rats at 18-day gestation was done. The cultured cells were divided into three groups: normoxia (N), hypoxia (H), and hypoxia treated with dizocilpine (HD). The N group was prepared in 5% $CO_2$ incubators and the other groups were placed in 1% $O_2$ incubators (94% N2, 5% $CO_2$) for 16 hours. In an in vivo model, left carotid artery ligation was done in 7-day-old SD rat pups. The animals were divided into six groups; hypoxia (N), hypoxia (H), hypoxia with sham-operation (HS), hypoxia with operation (HO), HO treated with vehicle (HV), and HO treated with dizocilpine (HD). Hypoxia was made by exposure to a 2 hour period of hypoxic incubator (92% N2, 8% $O_2$). Results: In the in vitvo and in vivo models, the expressions of Bcl-2 in the hypoxia groups were reduced compared to the normoxia group. whereas those in the dizocilpine-treated group were increased compared to the hypoxia group. However. the expressions of Bax and caspase-3 and the ratio of Bax/Bcl-2 were revealed reversely. Conclusion: Dizocilpine has neuroprotective property over perinatal HI brain injury via anti-apoptosis.

• The Korean Journal of Nuclear Medicine
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• v.37 no.2
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• pp.94-102
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• 2003

Purpose : Cerebral blood flow (CBF) reactivity to acetazolamide (ACZ) is useful to select patients with hemodynamic failure. However, it is still a matter of speculation that varying degrees of regional CBF increases after ACZ administration represent the severity or stage of regional hemodynamic failure as assessed by positron emission tomography (PET). We studied to elucidate whether ACZ challenge $^{123}I-IMP$ brain single photon emission tomography (SPECT) can accurately grade the seventy of regional hemodynamic failure. Materials and Methods: Eighteen patients (M: 16, F: 2, average age: 61 years) with unilateral occlusive disease of the internal carotid artery or the trunk of the middle cerebral artery (MCA). Patients undewent $^{123}I-IMP$ brain SPECT study with acetazolamide challenge and PET study was carried out within 2 weeks before and after SPECT study. Five healthy volunteers with a mean age of 48 years (range: 28-73 yr, M: 3, F: 2) underwent PET studies to determine normal values. In SPECT study, an asymmetry index (Al)-the percentage of radioactivity of region of interest (ROI) in the occlusive cerebrovascular lesion to the contralateral homologous ROI-was used for numerical evaluation of relative $^{123}I-IMP$ distribution. In PET study, regional CBF, oxygen extraction fraction (OEF), cerebral metabolic rate of oxygen ($CMRO_2$) and cerebral blood volume (CBV) values were measured with $^{15}O-labeled$ gas inhalation method and the values were used for comparison with Al (Al during acetazolamide challenge-Al of basal study) on the SPECT study. ROls were classified by severity into three groups (normal, stage I and stage II). Results: Mean values of Al in areas with normal, stage I and stage II hemodynamic failure were $6.25{\pm}7.77%\;(n=107),\;-10.38{\pm}10.41%\:(n=117)\;and\;13.30{\pm}10.51%\;(n=140)$, respectively. Al significantly differed with each groups (p<0.05). Correlation between Al and CBF, OEF and CBV/CBF in hemisphere with occlusive cerebrovascular lesion was 0.20 (p<0.01), -0.28 (p<0.01) and -0.28 (p<0.01), respectively. Conclusion: We concluded that $^{123}I-IMP$ brain SPECT with acetazolamide challenge could determine the severity ad stage of regional hemodynamic failure as assessed by PET.

• Journal of Chest Surgery
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• v.42 no.5
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• pp.588-596
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• 2009

Background: To clarify the effect of hypoxia on vascular contractility, we tried to show whether hypoxia induced the release of endothelium-derived relaxing factor (EDRF) and the nature of the underlying mechanism for this release. Material and Method: Isometric contractions were observed in rabbit aorta, and the released EDRF from the rabbit aorta was bioassayed by using rabbit denuded carotid artery. The intracellular $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) in the cultured rabbit aortic endothelial cells was recorded by a microfluorimeter with using Fura-2/AM. Hypoxia was evoked to the blood vessels or endothelial cells by eliminating the $O_2$ in the aerating gases in the external solution. Chemical hypoxia was evoked by applying deoxyglucose or $CN^-$. Result: Hypoxia relaxed the precontracted rabbit thoracic aorta that had its endothelium, and the magnitude of the relaxation was gradually increased by repetitive bouts of hypoxia. In contrast, hypoxia-induced relaxation was not evoked in the aorta that was denuded of endothelium. In a bioassay experiment, hypoxia released endothelium-derived relaxing factor (EDRF) and the release was inhibited by L-NAME or the $K^+$ channel blocker tetraethylammonium (TEA). In the cultured endothelial cells, hypoxia augmented the ATP-induced increase of the intracellular $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) and this increase was inhibited by TEA. Furthermore, chemical hypoxia also increased the $Ca^{2+}$ influx. Conclusion: From these results, it can be concluded that hypoxia might induce the release of NO from rabbit aortic endothelial cells by increasing $[[Ca^{2+}]_i$.

• International Journal of Vascular Biomedical Engineering
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• v.4 no.2
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• pp.19-24
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• 2006

Background: Pulse wave velocity (PWV), which is inversely related to the distensibility of an arterial wall, offers a simple and potentially useful approach for an evaluation of cardiovascular diseases. In spite of the clinical importance and widespread use of PWV, there exist no standard either for pulse sensors or for system requirements for accurate pulse wave measurement. Objective of this study was to assess the reproducibility of PWV values using a newly developed PWV measurement system in healthy subjects prior to a large-scale clinical study. Methods: System used for the study was the PP-1000 (Hanbyul Meditech Co., Korea), which provides regional PWV values based on the measurements of electrocardiography (ECG), phonocardiography (PCG), and pulse waves from four different sites of arteries (carotid, femoral, radial, and dorsalis pedis) simultaneously. Seventeen healthy male subjects with a mean age of 33 years (ranges 22 to 52 years) without any cardiovascular disease were participated for the experiment. Two observers (observer A and B) performed two consecutive measurements from the same subject in a random order. For an evaluation of system reproducibility, two analyses (within-observer and between-observer) were performed, and expressed in terms of mean difference ${\pm}2SD$, as described by Bland and Altman plots. Results: Mean and SD of PWVs for aorta, arm, and leg were $7.07{\pm}1.48m/sec,\;8.43{\pm}1.14m/sec,\;and\;8.09{\pm}0.98m/sec$ measured from observer A and $6.76{\pm}1.00m/sec,\;7.97{\pm}0.80m/sec,\;and\;\7.97{\pm}0.72m/sec$ from observer B, respectively. Between-observer differences ($mean{\pm}2SD$) for aorta, arm, and leg were $0.14{\pm\}0.62m/sec,\;0.18{\pm\}0.84m/sec,\;and\;0.07{\pm}0.86m/sec$, and the correlation coefficients were high especially 0.93 for aortic PWV. Within-observer differences ($mean{\pm}2SD$) for aorta, arm, and leg were $0.01{\pm}0.26m/sec,\;0.02{\pm}0.26m/sec,\;and\;0.08{\pm}0.32m/sec$ from observer A and $0.01{\pm}0.24m/sec,\;0.04{\pm}0.28m/sec,\;and\;0.01{\pm}0.20m/sec$ from observer B, respectively. All the measurements showed significantly high correlation coefficients ranges from 0.94 to 0.99. Conclusion: PWV measurement system used for the study offers comfortable and simple operation and provides accurate analysis results with high reproducibility. Since the reproducibility of the measurement is critical for the diagnosis in clinical use, it is necessary to provide an accurate algorithm for the detection of additional features such as flow wave, reflection wave, and dicrotic notch from a pulse waveform. This study will be extended for the comparison of PWV values from patients with various vascular risks for clinical application. Data acquired from the study could be used for the determination of the appropriate sample size for further studies relating various types of arteriosclerosis-related vascular disease.

• 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.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.6
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• pp.293-301
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• 2006

Purpose: The aim of the study was to evaluate the hemodynamic changes after successful bypass surgery in patients with atherosclerotic stenosis in ICA using $^{99m}Tc-ECD$ SPECT. Materials and Methods: Fourteen patients (M:F=8:6, mean age; $60{\pm}9$ years) who underwent STA-MCA anastomosis for unilateral atherosclerotic cerebrovascular disease were enrolled. $^{99m}Tc-ECD$ basal/acetazolamide perfusion SPECT studies were performed before, 10 days and 6 months after bypass surgery. Perfusion reserve was defined as the % changes after acetazolamide over rest image. Regional cerebral blood flow and perfusion reserve were compared preoperative, early-postoperative and late-postoperative scans. Results: The mean resting perfusion and decrease in perfusion reserve in affected ICA territory on preoperative scan was $52.4{\pm}3.5\;and\;-7.9{\pm}4.7%$, respectively. The resting perfusion was significantly improved after surgery on early-postoperative scan (mean $53.7{\pm}2.7$) and late-postoperative scan (mean $53.3{\pm}2.5$) compared with preoperative images (p<0.05, respectively). Resting perfusion did not showed further improvement on late-postoperative scan compared with early-postoperative scan. The perfusion reserve was $-3.7{\pm}2.6%$ on early-postoperative scan, and $-1.6{\pm}2.3%$ on late-postoperative scan, which was significantly improved after surgery. Additionally, further improvement of perfusion reserved as observed on late-postoperative scan (p<0.05). While, in the unaffected ICA territory, no significant changes in the resting perfusion and perfusion reserve was observed. Conclusion: The improvement of resting perfusion and perfusion reserve in early-postoperative scan reflects the immediate restoration of the cerebral blood flow by bypass surgery. In contrasts, further improvement of perfusion reserve showing on late-postoperative scan may indicate a good collateral development after surgery, which may indicate good surgical outcome after surgery.

• 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.

• Journal of Korean Neurosurgical Society
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• v.30 no.9
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• pp.1079-1085
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• 2001

Objective : We analysed various surgical approaches and surgical results of 28 middle cranial base tumors for the purpose of selecting optimal surgical approach to the middle cranial base tumor. Methods : In this retrospective review, 28 patients, including 16 meningioma, 6 trigeminal neurinoma, 2 pituitary adenoma, 2 craniopharyngioma, 1 facial neurinoma, and 1 metastatic tumor, underwent surgical treatment using skull base technique. Of theses, 16 tumors were mainly confined to middle cranial fossae, 5 tumors with extension into both anterior and middle fossa, and 7 tumors with extension into both middle and posterior fossa. Tumors that confined to the middle cranial fossa or extended into the anterior cranial fossa were operated with modified pterional, orbitozygomatic or Dolen'c approach, and tumors that extended into the posterior cranial fossa were operated with anterior, posterior or combined transpetrosal approach. Completeness of tumor resection, surgical outcome, postoperative complication, and follow up result were studied. Results : Total tumor removal was achieved in 9 tumors of 10 tumors that did not extended to the cavernous sinus, and was achieved in 7 tumors of 8 tumors that extended to the lateral wall of the cavernous sinus. Of 10 tumors that extended to the venous channel of the cavernous sinus, only 2 were removed totally. Surgical outcome was excellent in 14 patients, good in 10, fair in 2 and poor in 2. There were no death in this series. Dumbell type tumor which extended into both middle and posterior fossae showed tendency of poor prognosis as compared with tumors that confined middle cranial fossa and extended into both anterior and middle cranial fossa. Postoperative dysfunctions were trieminal hypesthesia in 3, oculomotor nerve palsy in 2, abducens nerve palsy in 2, hemiparesis in 2, cerebellar sign in 1, facial palsy in 1 and hearing impairment in 1. Conclusion : Based on our findings and a review of the literature, we conclude that, when selecting the surgical approach to the middle cranial fossa tumors, the most important factors to be considered were exact location of the tumor mass and existence of the cavernous sinus invasion by tumor mass. We recommend modified pterional or orbitozygomatic approach in cases with tumors located anterior and middle cranial base, without cavernous sinus invasion. In cases with tumors invading into cavernous sinus, we recommend Dolen'c or orbitozygomatic approach. And in lateral wall mass and the cavernous sinus, it is preferred to approach the tumor extradurally. For the tumor involing with middle fossa and posterior fossa(dumbell type) a combined petrosal approach is necessary. In cases with cavernous sinus invasion and internal carotid artery encasement, we recommend subtotal resection of the tumor and radiation therapy to prevent permanent postoperative sequele.

• Journal of Korean Neurosurgical Society
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• v.30 no.9
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• pp.1094-1102
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• 2001

Objective : During the trans-condylar or trans-jugular approach for the lesion of cranio-cervical junction(CCJ), its necessary to identify the accurate locations of vertebral artery(VA), internal jugular vein(IJV) and its related lower cranial nerves. These neurovascular structures can also be damaged during the operation for vascular tumor or traumatic aneurysm around extra-jugular foramen, because of their changed locations. To reduce the neurovascular injury at the operation for CCJ, morphometric relationship of its surrounding neurovascular structures based on the tip of the transverse process of atlas(C1 TP), were studied. Materials & Methods : Using 10 adult formalin fixed cadavers, tip of mastoid process(MT) and TPs of atlas and axis were exposed bilaterally after removal of occipital and posterior neck muscles. Using standard caliper, the distances were measured from the C1 TP to the following structures : 1) exit point of VA from C1 transverse foramen, 2) branching point of muscular artery from VA, 3) entry point of VA into posterior atlanto-occipital membrane(AOM), 4) branching point of C-1 nerve. In addition, the distances were measured from the mid-portion of the posterior arch of atlas to the entry point of the VA into AOM and to the exit point of the VA from C1 transverse foramen. After removal of the ventrolateral neck muscles, neurovascular structures were exposed in the extra-jugular foraminal region. Distances were then measured from the C1 TP to the following structures : 1) just extra-jugular foraminal IJV and lower cranial nerves, 2) MT and branching point of facial nerve in parotid gland. In addition, distance between MT and branching point of facial nerve was measured. Results : The VA was located at the mean distance of 12mm(range, 10.5-14mm) from the C1 transverse foramen and entered into the AOM at the mean distance of 24mm(range, 22.8-24.4mm) from the C1 TP. The mean distance from the mid portion of the C1 posterior arch was 20.6mm(range, 19.1-22.3mm) to the entry point of the VA into AOM and 38.4mm(range, 34-42.4mm) to the exit point of the VA from C1 transverse foramen. Muscular artery branched away from the posterior aspect of the transverse portion of VA below the occipital condyle at the mean distance of 22.3mm(range, 15.3-27.5mm) from the C1 TP. The C-1 nerve was identified in all specimens and ran downward through the ventroinferior surface of the transverse segment of VA and branched at the mean distance of 20mm(range, 17.7-20.3mm) from the C1 TP. The IJV was located at the mean distance of 6.7mm(range, 1-13.4mm) ventromedially from the lateral surface of the C1 TP. The XI cranial nerve ran downward on the lateral surface of the IJV at the mean distance of 5mm(range, 3-7.5mm) from the C1 TP. Both IX and X cranial nerves were located in the soft tissue between the medial aspect of the internal carotid artery(ICA) and the medial aspect of the IJV at the mean distance of 15.3mm(range, 13-24mm) and 13.7mm(range, 11-15.4mm) from the C1 TP, respectively. The IX cranial nerve ran downward ventroinferiorly crossing the lateral aspect of the ICA. The X cranial nerve ran downward posteroinferior to the IX cranial nerve and descended posterior to the ICA. The XII cranial nerve was located between the posteroinferior aspect of the IX cranial nerve and the posterior aspect of the ICA at the mean distance of 13.3mm(range, 9-15mm) ventromedially from the C1 TP. The distance between MT and C1 TP was 17.4mm(range, 12.5-23.9mm). The VII cranial nerve branched at the mean distance of 10.2mm(range, 6.8-15.3mm) ventromedially from the MT and at the mean distance of 17.3mm(range, 13-21mm) anterosuperiorly from the C1 TP. Conclusion : This study facilitates an understanding of the microsurgical anatomy of CCJ and may help to reduce the neurovascular injury at the surgery around CCJ.

• 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.