• Nuclear Medicine and Molecular Imaging
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• 제41권2호
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• pp.91-96
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• 2007

The measurement of pathologically low levels of tissue $pO_2$ is an important diagnostic goal for determining the prognosis of many clinically important diseases including cardiovascular insufficiency, stroke and cancer. The target tissues nowaday have mostly been tumors or the myocardium, with less attention centered on the brain. Radiolabelled nitroimidazole or derivatives may be useful in identifying the hypoxic cells in cerebrovascular disease or traumatic brain injury, and hypoxic-ischemic encephalopathy. In acute stroke, the target of therapy is the severely hypoxic but salvageable tissue. $^{18}F-MISO$ PET and $^{99}mTc-EC-metronidazole$ SPECT in patients with acute ischemic stroke identified hypoxic tissues and ischemic penumbra, and predicted its outcome. A study using $^{123}I-IAZA$ in patient with closed head injury detected the hypoxic tissues after head injury. Up till now these radiopharmaceuticals have drawbacks due to its relatively low concentration with hypoxic tissues associated with/without low blood-brain barrier permeability and the necessity to wait a long time to achieve acceptable target to background ratios for imaging in acute ischemic stroke. It is needed to develop new hypoxic marker exhibiting more rapid localization in the hypoxic region in the brain. And then, the hypoxic brain imaging with imidazoles or non-imidazoles may be very useful in detecting the hypoxic tissues, determining therapeutic strategies and developing therapeutic drugs in several neurological disease, especially, in acute ischemic stroke.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-1
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• pp.104-105
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• 2003

Hypoxic-ischemic (H-I) encephalopathy in the prenatal and perinatal period is a major cause of morbidity and mortality and often results in cognitive impairment, seizures, and motor impairment (cerebral palsy). Many studies of neonatal H-I brain injury have utilized the well characterized Levine model in which unilateral carotid ligation is followed by exposure to hypoxia. (omitted)

• Clinical and Experimental Pediatrics
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• 제49권2호
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• pp.198-202
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• 2006

목 적 : Fas는 세포표면 수용체로 세포사멸 신호를 전도한다. 많은 질환에서 세포표면의 Fas가 Fas ligand(FasL)와 결합하여 세포사멸 과정을 유발하게 된다. 연구자들은 7일된 신생 흰쥐에 저산소성 허혈성 손상을 유발한 후 뇌 해마에서 Fas와 FasL의 발현을 관찰하고자 하였다. 방 법 : 7일된 신생 흰쥐를 오른쪽 총 경동맥 영구 결찰 후 8% 산소에 2시간 노출시켰다. 저산소성 허혈성 손상 후 12, 24, 48시간에 뇌를 적출 냉동 보관하였다. Western blotting 방법과 면역형광염색 방법으로 냉동 보관된 뇌의 경동맥을 결찰한 오른 쪽 해마에서 Fas와 FasL의 발현을 관찰하였다. 결 과 : Fas와 FasL의 발현은 저산소성 허혈성 손상 후 12시간에 경동맥이 결찰된 오른쪽 해마에서 크게 증가하고 이후 감소하는 것을 western blotting 방법에 의해 관찰하였다. Fas와 FasL의 면역형광발현은 오른쪽 해마의 CA1 영역에서 손상 후 12시간과 24시간에 대조군에 비해 증가하였다. Fas의 면역형광 발현은 손상 후 48시간에 감소하였으나 FasL의 면역형광발현은 손상 후 48시간에도 지속되었다. 결 론 : 세포표면에서 Fas와 FasL의 발현과 그들의 결합은 저산소성 허혈성 손상을 받은 미성숙 뇌의 신경세포 손상에 기여할 것으로 추측되었다.

• Clinical and Experimental Pediatrics
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• 제64권12호
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• pp.608-618
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• 2021

Hypoxic-ischemic encephalopathy (HIE) is the most common cause of neonatal encephalopathy with a global incidence of approximately 1 to 8 per 1,000 live births. Neonatal encephalopathy can cause neurodevelopmental and cognitive impairments in survivors of hypoxic-ischemic insults with and without functional motor deficits. Normal neurodevelopmental outcomes in early childhood do not preclude cognitive and behavioral difficulties in late childhood and adolescence because cognitive functions are not yet fully developed at this early age. Therapeutic hypothermia has been shown to significantly reduced death and severe disabilities in term newborns with HIE. However, children treated with hypothermia therapy remain at risk for cognitive impairments and follow-up is necessary throughout late childhood and adolescence. Novel adjunctive neuroprotective therapies combined with therapeutic hypothermia may enhance the survival and neurodevelopmental outcomes of infants with HIE. The extent and severity of brain injury on magnetic resonance imaging might predict neurodevelopmental outcomes and lead to targeted interven tions in children with a history of neonatal encephalopathy. We provide a summary of the long-term cognitive outcomes in late childhood and adolescence in children with a history of HIE and the association between pattern of brain injury and neurodevelopmental outcomes.

• Biomolecules & Therapeutics
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• 제17권3호
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• pp.270-275
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• 2009

Polyethylene glycol-conjugated hemoglobin (PEG-Hb) has been proposed as a blood substitute for transfusion due to their plasma expansion and oxygen transport capabilities. The protective effect of PEG-Hb on cerebral hypoxic-ischemic injury was investigated in neonatal hypoxia model and adult rat focal cerebral ischemia model. As intravenously administered 30 min before the onset of hypoxia, PEG-Hb markedly protected cerebral hypoxic injury in a neonatal rat hypoxia model. A similar treatment of PEG-Hb largely reduced the ischemic injury ensuing after 2-h middle cerebral artery occlusion followed by 22-h reperfusion. Consistently, neurological disorder was significantly improved by PEG-Hb. The results indicate that the pharmacological blockade of cerebral ischemic injury by using PEG-Hb may provide a useful strategy for the treatment of cerebral stroke.

• Journal of Korean Neurosurgical Society
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• 제47권2호
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• pp.89-94
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• 2010

Objective : To evaluate the role of cranial sonography and computed tomography in the diagnosis of neonatal intracranial hemorrhage and hypoxic-ischemic injury in an Indian set-up. Methods : The study included 100 neonates who underwent cranial sonography and computed tomography (CT) in the first month of life for suspected intracranial ischemia and hemorrhage. Two observers rated the images for possible intracranial lesions and a kappa statistic for interobserver agreement was calculated. Results : There was no significant difference in the kappa values of CT and ultrasonography (USG) for the diagnosis of germinal matrix hemorrhage/intraventricular hemorrhage (GMH/IVH) and periventricular leucomalacia (PVL) and both showed good interobserver agreement. USG, however detected more cases of GMH/IVH (24 cases) and PVL (19) cases than CT (22 cases and 16 cases of IVH and PVL, respectively). CT had significantly better interobserver agreement for the diagnosis of hypoxic ischemic injury (HII) in term infants and also detected more cases (33) as compared to USG (18). CT also detected 6 cases of extraaxial hemorrhages as compared to 1 detected by USG. Conclusion : USG is better modality for imaging preterm neonates with suspected IVH or PVL. However, USG is unreliable in the imaging of term newborns with suspected HII where CT or magnetic resonance image scan is a better modality.

• 재활치료과학
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• 제7권1호
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• pp.11-26
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• 2018

목적 : 본 사례연구는 자살시도로 인한 저산소성 허혈성 뇌손상 환자의 특징적 증상과 신경학적 회복 양상을 고려한 인지 및 연하 재활 중심의 작업치료 중재를 소개하고 중재 효과로 인한 회복 양상에 대해 알아보고자 하였다. 연구방법 : 연구 대상은 자살시도로 인한 저산소성 허혈성 뇌손상을 진단받은 32세 남성으로 치료기간은 2016년 9월 8일부터 12월 6일까지이며, 주 5회 하루 한 번 재활치료를 받았다. 작업치료는 신경학적 기전으로 인한 저산소 허혈성 뇌손상의 특징과 자살이라는 정신 건강학적 특징을 바탕으로 이루어 졌으며, 인지와 연화 재활 중심의 프로그램이었다. 인지기능은 Mini Mental State Examination-Korean(MMSE-K), Computerized Neurocognitive Function Test(CNT), 일상생활활동 수준은 Korean-Modified Barthel Index(K-MBI), 연하기능은 Videofluoroscopic Dysphagia Scale(VDS), American Speech-Language-Hearing Association National Outcomes Measurements System (ASHA-NOMS)로 평가하였다. 결과 : 저산소성 허혈성 뇌손상 환자의 지연성 뇌손상 기전에 따라 인지기능 평가인 MMSE-K, CNT와 일상생활활동 수준을 평가하는 K-MBI, 연하기능을 평가하는 VDS, ASHA NOMS 결과에서 초기 평가 결과에 비해 모든 기능에서 저하가 나타났으나 회복 기전과 함께 재활 치료가 병행되며 모든 기능이 회복되어 초기 평가 수준으로 호전되었다. 결론 : 본 연구 결과 자살시도로 인한 심리적 요인과 저산소성 허혈성 뇌손상으로 인한 인지 및 연하적 요인을 고려한 일반적인 작업치료 프로그램은 환자에게 긍정적 회복 양상을 나타냈다. 이를 바탕으로 저산소성 허혈성 뇌손상으로 인한 지연성 뇌손상이 발생한 환자에게 작업치료의 개입은 필요한 부분이며, 정신건강과 인지 및 연하기능의 중심 프로그램이 개발되어야할 것이다.

• BMB Reports
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• 제35권1호
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• pp.67-86
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• 2002

Three routes have been identified triggering neuronal death under physiological and pathological conditions. Excess activation of ionotropic glutamate receptors cause influx and accumulation of $Ca^{2+}$ and $Na^+$ that result in rapid swelling and subsequent neuronal death within a few hours. The second route is caused by oxidative stress due to accumulation of reactive oxygen and nitrogen species. Apoptosis or programmed cell death that often occurs during developmental process has been coined as additional route to pathological neuronal death in the mature nervous system. Evidence is being accumulated that excitotoxicity, oxidative stress, and apoptosis propagate through distinctive and mutually exclusive signal transduction pathway and contribute to neuronal loss following hypoxic-ischemic brain injury. Thus, the therapeutic intervention of hypoxic-ischemic neuronal injury should be aimed to prevent excitotoxicity, oxidative stress, and apoptosis in a concerted way.

• Biomolecules & Therapeutics
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• 제24권5호
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• pp.495-500
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• 2016

This study aimed to explore the neuroprotection and mechanism of isoflurane on rats with spinal cord ischemic injury. Total 40 adult male Sprague-Dawley rats were divided into the four groups (n=10). Group A was sham-operation group; group B was ischemia group; group C was isoflurane preconditioning group; group D was isoflurane preconditioning followed by ischemia treatment group. Then the expressions of TWIK-related $K^+$ channel 1 (TREK1) in the four groups were detected by immunofluorescent assay, real time-polymerase chain reactions (RT-PCR) and western blot. The primary neurons of rats were isolated and cultured under normal and hypoxic conditions. Besides, the neurons under two conditions were transfected with green fluorescent protein (GFP)-TREK1 and lentivirual to overexpress and silence TREK1. Additionally, the neurons were treated with isoflurane or not. Then caspase-3 activity and cell cycle of neurons under normal and hypoxic conditions were detected. Furthermore, nicotinamide adenine dinucleotide hydrate (NADH) was detected using NAD+/NADH quantification colorimetric kit. Results showed that the mRNA and protein expressions of TREK1 increased significantly in group C and D. In neurons, when TREK1 silenced, isoflurane treatment improved the caspase-3 activity. In hypoxic condition, the caspase-3 activity and sub-G1 cell percentage significantly increased, however, when TREK1 overexpressed the caspase-3 activity and sub-G1 cell percentage decreased significantly. Furthermore, both isoflurane treatment and overexpression of TREK1 significantly decreased NADH. In conclusion, isoflurane-induced neuroprotection in spinal cord ischemic injury may be associated with the up-regulation of TREK1.

• Molecules and Cells
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• 제45권4호
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• pp.216-230
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• 2022

SERTA domain-containing protein 1 (Sertad1) is upregulated in the models of DNA damage and Alzheimer's disease, contributing to neuronal death. However, the role and mechanism of Sertad1 in ischemic/hypoxic neurological injury remain unclear. In the present study, our results showed that the expression of Sertad1 was upregulated in a mouse middle cerebral artery occlusion and reperfusion model and in HT22 cells after oxygen-glucose deprivation/reoxygenation (OGD/R). Sertad1 knockdown significantly ameliorated ischemia-induced brain infarct volume, neurological deficits and neuronal apoptosis. In addition, it significantly ameliorated the OGD/R-induced inhibition of cell viability and apoptotic cell death in HT22 cells. Sertad1 knockdown significantly inhibited the ischemic/hypoxic-induced expression of p-Rb, B-Myb, and Bim in vivo and in vitro. However, Sertad1 overexpression significantly exacerbated the OGD/R-induced inhibition of cell viability and apoptotic cell death and p-Rb, B-Myb, and Bim expression in HT22 cells. In further studies, we demonstrated that Sertad1 directly binds to CDK4 and the CDK4 inhibitor ON123300 restores the effects of Sertad1 overexpression on OGD/R-induced apoptotic cell death and p-Rb, B-Myb, and Bim expression in HT22 cells. These results suggested that Sertad1 contributed to ischemic/hypoxic neurological injury by activating the CDK4/p-Rb pathway.