Neuroprotective effects of geneticin (G418) via apoptosisin perinatal hypoxic-ischemic brain injury

주미,이현주,이선주,서억수,박혜진,이계향,이경훈,최은진,김진경,이종원,정혜리,김우택 대한소아청소년과학회 2008 Clinical and Experimental Pediatrics (CEP) Vol.51 No.2

Purpose:Some antibiotics were known to exert neuroprotective effects in the animal model of hypoxic-ischemic (H-I) brain injury, but the mechanism is still unclear. A recent study reported that geneticin (G418), an aminoglycoside antibiotic, increased survival of human breast cancer cells by suppressing apoptosis. We investigated the neuroprotective effects of systemically administrated geneticin via anti-apoptosis following the H-I brain injury Methods:Seven-day-old Sprague-Dawley rat pups were subjected to unilateral (left) common carotid artery occlusion followed by 2.5 hours of hypoxic exposure and the cortical cell culture of rat brain was done under a hypoxic incubator. Apoptosis was measured in the injured hemispheres 7 days after H-I insult and in the injured cells from hypoxic chamber using morphologic analysis by Terminal dUTP Nick-end Labeling(TUNEL) assay and immunohistochemistry for caspase-3, and cytologic analysis by western blot and real time PCR for bax, bcl-2, and caspase-3. Results:The gross appearance and hematoxylin and eosin stain revealed increased brain volume in the geneticin-treated animal model of perinatal H-I brain injury. The TUNEL assay revealed decreased apoptotic cells after administration of geneticin in the cell culture model of anoxia. Immunohistochemistry showed decreased caspase-3 expression in geneticin-treated cortical cell culture. Western blot and real-time PCR showed decreased caspase-3 expression and decreased ratio of Bax/ Bcl-2 expression in geneticin-treated animal model. Conclusion:Geneticin appears to exert a neuroprotective effect against perinatal H-I brain injury at least via anti-apoptosis. However, more experiments are needed in order to demonstrate the usefulness of geneticin as a preventive and rescue treatment for H-I brain injuries of neonatal brain. (Korean J Pediatr 2008;51:170-180) Purpose:Some antibiotics were known to exert neuroprotective effects in the animal model of hypoxic-ischemic (H-I) brain injury, but the mechanism is still unclear. A recent study reported that geneticin (G418), an aminoglycoside antibiotic, increased survival of human breast cancer cells by suppressing apoptosis. We investigated the neuroprotective effects of systemically administrated geneticin via anti-apoptosis following the H-I brain injury Methods:Seven-day-old Sprague-Dawley rat pups were subjected to unilateral (left) common carotid artery occlusion followed by 2.5 hours of hypoxic exposure and the cortical cell culture of rat brain was done under a hypoxic incubator. Apoptosis was measured in the injured hemispheres 7 days after H-I insult and in the injured cells from hypoxic chamber using morphologic analysis by Terminal dUTP Nick-end Labeling(TUNEL) assay and immunohistochemistry for caspase-3, and cytologic analysis by western blot and real time PCR for bax, bcl-2, and caspase-3. Results:The gross appearance and hematoxylin and eosin stain revealed increased brain volume in the geneticin-treated animal model of perinatal H-I brain injury. The TUNEL assay revealed decreased apoptotic cells after administration of geneticin in the cell culture model of anoxia. Immunohistochemistry showed decreased caspase-3 expression in geneticin-treated cortical cell culture. Western blot and real-time PCR showed decreased caspase-3 expression and decreased ratio of Bax/ Bcl-2 expression in geneticin-treated animal model. Conclusion:Geneticin appears to exert a neuroprotective effect against perinatal H-I brain injury at least via anti-apoptosis. However, more experiments are needed in order to demonstrate the usefulness of geneticin as a preventive and rescue treatment for H-I brain injuries of neonatal brain. (Korean J Pediatr 2008;51:170-180)

Neuroprotective effects of resveratrol via anti-apoptosis on hypoxic-ischemic brain injury in neonatal rats

신진영,서민애,최은진,김진경,서억수,이준화,정혜리,김우택 대한소아청소년과학회 2008 Clinical and Experimental Pediatrics (CEP) Vol.51 No.10

Purpose : Resveratrol, extracted from red wine and grapes, has an anti-cancer effect, an antiinflammatory effect, and an antioxidative effect mainly in heart disease and also has neuroprotective effects in the adult animal model. No studies for neuroprotective effects during the neonatal periods have been reported. Therefore, we studied the neuroprotective effect of resveratrol on hypoxic-ischemic brain damage in neonatal rats via anti-apoptosis. Methods : Embryonic cortical neuronal cell culture of rat brain was performed using pregnant Sprague-Dawley (SD) rats at 18 days of gestation (E18) for the in vitro approach. We injured the cells with hypoxia and administered resveratrol (1, 10, and 30 µg/mL) to the cells at 30 minutes before hypoxic insults. In addition, unilateral carotid artery ligation with hypoxia was induced in 7-day-old neonatal rats for the in vivo approach. We injected resveratrol (30 mg/kg) intraperitoneally into animal models. Real-time PCR and Western blotting were performed to identify the neuroprotective effects of resveratrol through anti-apoptosis. Results : In the in vitro approach of hypoxia, the expression of Bax, caspase-3, and the ratio of Bax/Bcl-2, indicators of the level of apoptosis, were significantly increased in the hypoxia group compared to the normoxia group. In the case of the resveratrol-treated group, expression was significantly decreased compared to the hypoxia group. And the results in the in vivo approach were the same as in the in vitro approach. Conclusion : The present study demonstrates that resveratrol plays neuroprotective role in hypoxic-ischemic brain damage during neonatal periods through the mechanism of anti-apoptosis. Purpose : Resveratrol, extracted from red wine and grapes, has an anti-cancer effect, an antiinflammatory effect, and an antioxidative effect mainly in heart disease and also has neuroprotective effects in the adult animal model. No studies for neuroprotective effects during the neonatal periods have been reported. Therefore, we studied the neuroprotective effect of resveratrol on hypoxic-ischemic brain damage in neonatal rats via anti-apoptosis. Methods : Embryonic cortical neuronal cell culture of rat brain was performed using pregnant Sprague-Dawley (SD) rats at 18 days of gestation (E18) for the in vitro approach. We injured the cells with hypoxia and administered resveratrol (1, 10, and 30 µg/mL) to the cells at 30 minutes before hypoxic insults. In addition, unilateral carotid artery ligation with hypoxia was induced in 7-day-old neonatal rats for the in vivo approach. We injected resveratrol (30 mg/kg) intraperitoneally into animal models. Real-time PCR and Western blotting were performed to identify the neuroprotective effects of resveratrol through anti-apoptosis. Results : In the in vitro approach of hypoxia, the expression of Bax, caspase-3, and the ratio of Bax/Bcl-2, indicators of the level of apoptosis, were significantly increased in the hypoxia group compared to the normoxia group. In the case of the resveratrol-treated group, expression was significantly decreased compared to the hypoxia group. And the results in the in vivo approach were the same as in the in vitro approach. Conclusion : The present study demonstrates that resveratrol plays neuroprotective role in hypoxic-ischemic brain damage during neonatal periods through the mechanism of anti-apoptosis.

Taurine exerts neuroprotective effects via anti-apoptosis in hypoxic-ischemic brain injury in neonatal rats

정지은,김태열,박혜진,이계향,이정훈,최은진,김진경,정혜리,서억수,김우택 대한소아청소년과학회 2009 Clinical and Experimental Pediatrics (CEP) Vol.52 No.12

Purpose:Taurine (2-aminoethanesulfonic acid) is a simple sulfur-containing amino acid. It is abundantly present in tissues such as brain, retina, heart, and skeletal muscles. Current studies have demonstrated the neuroprotective effects of taurine, but limited data are available for such effects during neonatal period. The aim of this study was to determine whether taurine could reduce hypoxic-ischemic (HI) cerebral injury via anti-apoptosis mechanism. Methods:Embryonic cortical neurons isolated from Sprague-Dawley (SD) rats at 18 days gestation were cultured in vitro. The cells were divided into hypoxia group, taurine-treated group before hypoxic insult, and taurine-treated group after HI insult. In the in vivo model, left carotid artery ligation was performed in 7-day-old SD rat pups. The pups were exposed to hypoxia, administered an injection of 30 mg/kg of taurine, and killed at 1 day, 3 days, 1 week, 2 weeks, and 4 weeks after the hypoxic insult. We compared the expressions of Bcl-2, Bax, and caspase-3 among the 3 groups by using real- time polymerase chain reaction (PCR) and western blotting. Results:The cells in the taurine-treated group before hypoxic insult, although similar in appearance to those in the normoxia group, were lesser in number. In the taurine-treated group, Bcl-2 expression increased, whereas Bax and caspase-3 expressions reduced. Conclusion:Taurine exerts neuroprotective effects onperinatal HI brain injury due to its anti-apoptotic effect. The neuroprotective effect was maximal at 1–2 weeks after the hypoxic injury. Purpose:Taurine (2-aminoethanesulfonic acid) is a simple sulfur-containing amino acid. It is abundantly present in tissues such as brain, retina, heart, and skeletal muscles. Current studies have demonstrated the neuroprotective effects of taurine, but limited data are available for such effects during neonatal period. The aim of this study was to determine whether taurine could reduce hypoxic-ischemic (HI) cerebral injury via anti-apoptosis mechanism. Methods:Embryonic cortical neurons isolated from Sprague-Dawley (SD) rats at 18 days gestation were cultured in vitro. The cells were divided into hypoxia group, taurine-treated group before hypoxic insult, and taurine-treated group after HI insult. In the in vivo model, left carotid artery ligation was performed in 7-day-old SD rat pups. The pups were exposed to hypoxia, administered an injection of 30 mg/kg of taurine, and killed at 1 day, 3 days, 1 week, 2 weeks, and 4 weeks after the hypoxic insult. We compared the expressions of Bcl-2, Bax, and caspase-3 among the 3 groups by using real- time polymerase chain reaction (PCR) and western blotting. Results:The cells in the taurine-treated group before hypoxic insult, although similar in appearance to those in the normoxia group, were lesser in number. In the taurine-treated group, Bcl-2 expression increased, whereas Bax and caspase-3 expressions reduced. Conclusion:Taurine exerts neuroprotective effects onperinatal HI brain injury due to its anti-apoptotic effect. The neuroprotective effect was maximal at 1–2 weeks after the hypoxic injury.

신생 흰쥐 대뇌의 바닥핵에서 허혈-저산소손상에 의한 신경세포의 Apoptosis와 AIF의 발현양상의 변화에 관한 분석

이영일(Young Il Lee) 대한해부학회 2006 Anatomy & Cell Biology Vol.39 No.1

The caudate-putamen is generally referred to as the striatum or neostriatum, which is one of the main components of the basal ganglia and this designation, is especially relevant in the rat. In spite of the fact that it comprises one of the major parts in central nervous system, studies on how seriously vulnerable this area to cerebral ischemia especially in neonates is still remained. In this study, using neonatal (7 days postnatal) rats, we speculated the significance of AIF in the apoptotic neuronal cell death in basal ganglia induced by hypoxic-ischemic injury. For this study, we introduced permanent common carotid artery occlusion and then, exposed to 6% oxygen for 2 hours and the results are as follows: 1. There were tendency of increasing AIF immunoreactivity induced by hypoxic-ischemic insult in neonatal basal ganglia at 12 & 24 hrs after hypoxic-ischemic insult. 2. Western Blotting analysis showed increased AIF expression in basal ganglia at 12 hrs (caudate-putamen) & 24 hrs (globus pallidus) after hypoxic-ischemic insult. 3. Evidence of localization of AIF in glial cells as well as in neurons obtained by double-immunofluorescence staining. Our results seem to provide evidences on the involvement of AIF in the apoptotic neuronal cell loss with hypoxicischemic insult in neonatal rat. Furthermore, localization AIF in glial cells as well as in neurons suggests involvement of neuroglial cells in the apoptotic pathway in neonatal basal ganglia induced by hypoxic-ischemic injury. 흰쥐 뇌의 바닥핵(basal ganglia)을 이루는 주요 구성성분인 꼬리조가비핵(caudate-putamen)과 창백핵(globus pallidus)에서의 허혈-저산소손상(hypoxic ischemic injury)에 의한 AIF (apoptosis inducing factor)의 시간에 따른 발현양 변화를 생후 7일 된 신생흰쥐의 허혈-저산소모델을 이용해 확인하고 이를 정량분석하였다. 바닥핵에서의 AIF의 발현변화는 수술 후 꼬리조가비핵에서는 12시간 경과 후에, 그리고 창백핵에서는 24시간 경과후에 가장 높게 나타났으며 48시간 경과군에서는 다시 대조군의 수준 또는 그 이하로 감소되어 나타났다. 또한 본 연구에서는 AIF의 발현이 신경세포에만 국한되어 나타나는 것인지 여부를 신경세포와 신경아교세포(neuroglial cell)에 대한 이중면역형광염색 (double-immunofluorescence staining)을 통해 알아봄으로써 미성숙한 뇌에서 허혈-저산소손상에 의한 AIF의 작용기전이 신경세포는 물론 바닥핵을 구성하는 신경아교세포에서도 나타남을 확인하였다. AIF는 허혈-저산소손상으로 인한 미성숙 뇌의 바닥핵에서의 세포자멸사(apoptosis) 기전과 깊은 관련이 있음이 확인되었으며 이는 뇌허혈에 취약한 미성숙 신경세포의 손상기전을 연구하는데 있어서 중요한 단서를 제공할 것으로 판단된다. 아울러 뇌허혈을 비롯한 급성뇌손상으로부터 신경세포를 보호하기 위한 치료법 개발에 있어서 AIF와 관련된 병태생리의 중요성은 더욱 부각될 것으로 전망된다.

Effects of Dexamethasone in Hypoxic-Ischemic Brain Injury in the Rats : 저산소성 병변에서의 덱사메타존의 영향

Koo, Heasoo 梨花女子大學校 醫科大學 醫科學硏究所 1993 EMJ (Ewha medical journal) Vol.16 No.2

급성 척수 손상과 뇌종양 등의 혈관성 부종을 동반하는 질환이 있는 환자에서 담질 코르티코이드를 다량 사용하는 경우 좋은 효과를 보이는 것은 잘 알려져 있고 현재에도 치료의일환으로 사용되고 있다. 그러나 허혈-저산소성 병변에서는 임상실험이나 실험동물에서 모두효과가 없거나 오히려 뇌세포의 손상을 악화시키므로 더 이상 사용이 금지되고 있다. 근래에시행된 한 실험에서 여태까지의 보고들과는 달리 7일 된 미성숙취에서 허혈-저산소성 병변이일어나기 전에 덱사메타존을 여러 번으로 나눠서 투여하는 경우 뇌세포의 손상을 적게 하는것이 관찰되었고 이러한 소견은 임상에서 미 성숙아에서 제의 기능을 증가시키기 위해 출생전후에 텍사메타존의 투여를 시도하므로 중요한 의미를 갖는다. 본 실험에서는 덱사메타존을투여방법과 용량을 다르게 투여하여 그에 따른 뇌세포의 손상을 관찰하였다. 덱사메타존 0.5mg/kg와 2.Omg/kg를 3회 전처치한 실험동물군이나 1.Omg/kg를 3회 후처치군에서 신경세포의손상에 의미있는 차이가 없었으며 단지 후처치군에서 해마의 일부에서 다른 군보다 더 심한손상을 보였다. 이러한 실험결과는 미성숙쥐와 성숙쥐에서 발생하는 허혈-저산소성 병변은그 기전이나 병변에 관여하는 여러가지 요소가 다른 것을 의미하고 그러한 요소들에 대한앞으로의 연구가 필수적이라고 생각된다. 또한 허혈-저산소성 병변에서 담질 코르터코이드의사용이 금지되어야 하는 것을 뒷받침한다. The efffect of high dose of glucocorticoid in acute spinal cord injury has been well provedexperimentally and clinically. In addition. the beneficial efffect of steroids in cerebral vasogenicedema has been well documented and clinically steroids are now a part of the treatment ofintracranial neoplasms. Consequent trials of high dose steroid therapy in CNS injury havebeen proved its ineffectiveness or adverse effecis in clinical and experimental studies. Also.dexamethasone treatment in hypoxic-ischemic brain damage in rats showed adverse effectson neurons in most of the studies in adult and immature rats, except one report which showedneuroprotective effects of dexamethasone pretreatment in 7-day-old immature rats. This study was designed to see if there was same neuroprotective effect in adult rat sinceno previous experiments used same amounts of steroid at this time intervals. Hypoxic-ischemicinjury was induced in adult Sprague-Dawley rats, 150∼240 gms, by Levine procedure withsome modification (left carotid artery ligation and exposure to 8% oxygen-92% nitrogen gasfor 2 hours). The animals were divided into four groups and dexamethasone was injectedas follows : (Ⅰ) hypoxic-ischemic control group without dexamethasone injection(n= 16) ; (Ⅱ)0.5fmg/kg i.p. 3 times, 48 and 24 hours, and immediately before the carotid artery ligationand 8% oxygen treatment(n=16) ; (Ⅲ) 2.Omg/kg at same time with (Ⅱ) (n=14) ; (Ⅳ)1.Ogm/kg 3 times at immediately after.24 and 48 hours after the procedure(n=20). The neuropa-thological changes were interpreted 7 days after the procedure. The results are summarized as follows : 1) In hypoxic-ischemic control group(Ⅰ), 5 out of 16 rats(31.3%) of rats showed large infarctioninvolving ipsilateral side of the brain and other 4∼5 rats showed severe neuronal damagein anterior and posterior cortex. hippocampus. striatum, and thalamus. 2) Compare to control group. dexamethasone 0.5mg/kg 3 times pretreatment group(Ⅱ) showedsimilar neuronal damage in all areas, although the infaction was focal in striatum and thalamus in group Ⅱ and generalized in group Ⅰ. The changes were not statistically significant. 3) Group Ⅲ showed no significant difference from groups Ⅰ, Ⅱ, and Ⅳ. 4) Group Ⅳ showed more neuronal damage in CA1-2 area of hippocampus compare togroups Ⅰ and Ⅱ(p<0.01, p<0.005. respectively). 5) Mortality rate was not significantly different between groups. In conclusion, dexamethasone pretreatment did not improve hypoxic-ischemic neuronal da-mage in adult rats. Dexamethasone posttreatment aggravated neuronal damages in CA1-2 areaof hippocampus compare to control and pretreatment groups.

허혈성 저산소증으로 유도한 신경 세포 소실시의 치상회 태상 섬유의 발아 유무에 대한 관찰

문한구(Han-Ku Moon),이은실(Eun Sil Lee),신손문(Son Moon Shin),박용훈(Yong Hoon Park) 대한소아신경학회 1998 대한소아신경학회지 Vol.6 No.1

목 적 : 측두엽 간질의 실험 동물이나 환자에서 흔히 관찰되는 해마 태상 섬유 발아는 해마에서의 세포 소실이 중요한 요인이며 세포 소실의 정도가 심할수록 발아의 정도는 증가한다고 알려져 있지만 미성숙 뇌를 허혈성 저산소증에 노출시켜 해마의 세포 소실을 유도하여도 태상 섬유 발아는 관찰할 수 없었다는 보고가 있다. 그러나 미성숙 뇌의 경우 여러 가지 손상에 대한 신경계의 변화는 성숙 뇌에서의 반응과 일치하지 않는 경우가 많다. 본 연구는 인간에 있어서 사춘기에 속하는 생후 4-5주 연령 및 성인기에 해당하는 생후 2개월 연령의 횐 쥐들을 허혈성 저산소증에 노출시켜 해마의 세포 손상을 유발한 후 해마 태상 섬유 발아 가 유도되는지 여부를 알고자 시행되었다. 방 법 : 생후 4-5주 및 2개월 연령의 Sprague-Dawley를 우측 경동맥 결찰 후 8%의 저농도 산소에 각각 90분, 50분동안 노출시켜 허혈성 저산소증을 유발한 뒤 2주 경과 후까지 생존한 생후 4-5주 연령군 (대조군 4마리, 실험군 5마리)과 2개월 연령군 (대조군 4마리, 실험 군 6마리) 횐 쥐의 뇌 조직을 추출하여 일부는 H & I 염색을 시행하여 해마내의 세포 손상을 확인하고 일부는 냉동절편 후 중금속 염색법인 Timm 염색을 시행하여 태상 섬유 발아 여부를 관찰하여 각 군의 대조군과 비교하였다. 결 과 : 4-5 주 및 2 개월 연령군에서 허혈성 저산소군의 H & I 염색한 해마에서 다양한 정도의 문 세포, 추체 세포들의 허혈성 저산소증에 의한 변화가 관찰되었다. 그러나 Timm 염색을 시행한 허혈성 저산소군(4-5 주 연령군 5례, 2개월 연령군 6례)의 우측 해마의 과립 세포 상부층의 Timm 염색 정도는 대조군과 비교하여 유의한 차이가 없었다. 결 론 : 연소 및 성숙 횐 쥐를 허혈성 저산소증에 노출시켜 해마의 세포 손상을 유발한 후 태상 섬유 발아가 유도되는 지를 관찰하였으나 대조군에 비해 유의한 차이를 찾을 수 없었다 이를 미루어 보아 해마의 발아는 단순히 세포 소실에 의한 2차적인 현상이 아닌 다른 요인이 관여할 것으로 추정된다. Purpose : Reorganization of mossy fiber terminals in the supragranular layer of the dentate has been found in hippocampi of human epileptics and animal models by Timm staining. Many studies have provided evidence that mossy fiber sprouting is strongly associated with neuronal loss. But the question of whether cell loss is necessary for stimulation of mossy fiber sprouting is remained to be answered. In this present study, we evaluated whether hippocampal mossy fiber sprouting is induced in damaged hippo- campus of the rats exposed to hypoxic-ischemic insults in juvenile and adult period. Methods : At ages of f-5 weeks and 2 months, the experimental rats were received procedure of right carotid artery unilateral ligation under anesthesia. After 3 hours of the recovery period, they were placed in an airtight 2000m1 chamber and exposed to a 8% oxygen-92% nitrogen mixture delivered at 5 liter/min for 90 minutes(juvenile) and 50 minutes(adult). After the recovery period, The animals were returned to cages and housed controls. 2 weeks later, rats of the control and hypoxic-ischemia group were tonesthetised and then perfused with sodium sulfide solution and fixed. 40 # m(for Timm stain) and 5#m(for H & I stain) coronary brain sections were obtained, stained with Timm method and H & I stain for the observation of the neuronal loss and supragranular Timm granules in the hippocampi. Results : Light microscopic examination of the brains from hypoxic-ischemic animals demonstrated ischemic changes of variable degrees in the hippocampal hilar and pyramidal cell layers. No supragranular mossy fiber sprouting were found in hippocampi of juvenile and adult rats with hypoxic-ischemic damages. Conclusion : These results implicated that hippocampal mossy fiber sprouting is not induced in the experimental hypoxic-ischemic encephalopathy of juvenile and adult rats, although cellular loss is found in hippocampus. Neuronal loss might be not necessary for the development of mossy fiber sprouting.

저산소-허혈성 뇌병증 환자의 신경학적 회복 예측

윤서연,김제경,김용욱 대한뇌신경재활학회 2014 뇌신경재활 Vol.7 No.1

The incidence of hypoxic-ischemic encephalopathy (HIE) is not well known, however, the common causesof hypoxic-ischemic encephalopathy are sudden cardiac arrest, acute respiratory failure and carbonmonoxide poisoning. Due to high metabolic demand, the brain is very susceptible to damage fromdeprivation of blood supply and oxygen delivery. When patients recover from comatose after HIE, thereare various spectrums of neurological outcomes, ranging from vegetative state to good recovery. Variousmethods including neurologic examination, neurophysiologic and biochemical tools, neuroimaging techniquehave been proposed for the prognostic evaluation of HIE. This article reviews the pathophysiology ofHIE and predictive methods for neurological recovery after HIE.

Cognitive outcomes in late childhood and adolescence of neonatal hypoxic-ischemic encephalopathy

이보린,Glass Hannah C. 대한소아청소년과학회 2021 Clinical and Experimental Pediatrics (CEP) Vol.64 No.12

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.

Prediction of Neurodevelopmental Outcome in Hypoxic Ischemic Encephalopathy at 12 Months: Correlation of Brain MRI and EEG

( Hee Cheol Jo ),( Eun Jeong Kim ),( Jang Hoon Lee ),( Da Eun Jung ),( Moon Sung Park ),( Sung Hwan Kim ) 대한주산의학회 2015 大韓周産醫學會雜誌 Vol.26 No.3

Purpose: The aims of this study were to estimate the neurodevelopmental outcome of hypoxic-ischemic encephalopathy (HIE) at 12 months, and determine the usefulness of brain magnetic resonance imaging (MRI) and electroencephalography (EEG) to predict neurodevelopmental outcome in term infants with HIE at 12 months. Methods: This study was conducted retrospectively on term infants with HIE from January 2009 to June 2013. Based on neurodevelopmental outcome at 12 months, infants were categorized into 2 groups. Brain MRI and EEG findings were stratified into 4 categories as normal, mild, moderate and severe groups. Results: Total 42 term infants were enrolled. Fifty seven point one percent (24/42) of total infants had favorable neurodevelopmental outcome at 12 months (favorable outcome, n=24). Thirty eight point one percent (16/42) of total infants had significant neurodevelopmental deficit at 12 months of age, and 4.8% (2/42) had mortality within 12 months (poor outcome, n=18). In brain MRI and EEG findings, there were significant correlations with neurodevelopmental outcome. Brain MRI showed sensitivity of 88.9%, specificity of 70.8%, positive predictive value of 69.6% and negative predictive value of 89.5%, while EEG showed sensitivity of 70.6%, specificity of 82.6%, positive predictive value of 75%, and negative predictive value of 79.2%. In the multivariate analysis, moderatetosevere findings in brain MRI were the strongest risk factor (oddsratio, 11.24; 95% confidence interval, 1.3692.89; P=0.025). Conclusion: Forty two point nine percent of total infants had poor neurodevelopmental outcome at 12 months. Brain MRI and EEG findings were correlated with neurodevelopmental outcome of term infants with HIE at 12 months.

저산소 뇌허혈 백서에서 풍요한 환경이 운동과 인지 발달에 미치는 영향

양신승,김봉옥,최필순,김성겸,손민균 대한재활의학회 2010 Annals of Rehabilitation Medicine Vol.34 No.1

Objective: To investigate the effect of environmental enrichment on the cognitive and motor development in the experimental hypoxia-ischemic encephalopathy neonatal rat model. Method: Hypoxic-ischemic encephalopathy models were made in neonatal Sprague-Dawley rats at 3 days of age by ligating the unilateral carotid artery followed by inhalation of 8% oxygen and raised in the enriched environment (n=10), treadmill exercise (n=8) and non-stimulation (n=10) from the 3rd to 8th weeks of age. Neurobehavioral and histopathological changes were compared. Results: The neurobehavioral tests of the rats with hypoxic- ischemic encephalopathy showed prolonged latencies of achievement for cliff avoidance and negative geotaxis (p<0.05). Persisting abnormality into adult life of limb placing improved in exercise and enriched environment groups and spatial learning and memory in a water maze recovered in the rats with enriched environment (p<0.05). The density of dendritic spine increased in the hippocampus with enriched environment (p<0.05). Conclusion: The present study supports the possibilities of the positive effects after the enriched environment in the developing brain with hypoxic injury. (J Korean Acad Rehab Med 2010; 34: 1-9)