• 대한의생명과학회지
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• 제21권2호
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• pp.92-102
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• 2015

This work aimed to study whether rice bran extract fermented with Lactobacillus plantarum (LW) promotes functional recovery and reduces cognitive impairment after ischemic brain injury. Ischemic brain injury was induced by middle cerebral artery occlusion (MCAO) in rats. Four groups were studied, namely the (1) sham, (2) vehicle, (3) donepezil, and (4) LW groups. Animals were injected with LW once a day for 7 days after middle cerebral artery occlusion. LW group showed significantly improved neurological function as compared to the vehicle group, as well as enhanced learning and memory in the Morris water maze. The LW group showed the greatest functional recovery. Moreover, the LW group showed an enhanced more survival cells anti-apoptotic effect in the cortex and neural cell densities in the hippocampal DG and CA1. In addition, this group showed enhanced expression of neurotrophic factors, antioxidant genes, and the acetylcholine receptor gene, as well as synaptophysin (SYP), Fox-3 (NeuN), doublecortin (DCX), and choline acetyltransferase (ChAT) proteins. Our findings indicate that LW treatment showed the largest effects in functional recovery and cognitive improvement after ischemic brain injury through stimulation of the acetylcholine receptor, antioxidant genes, neurotrophic factors, and expression of NeuN, SYP, DCX, and ChAT.

• Biomolecules & Therapeutics
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• 제30권1호
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• pp.55-63
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• 2022

Oleanolic acid (OA), a natural pentacyclic triterpenoid, has been reported to exert protective effects against several neurological diseases through its anti-oxidative and anti-inflammatory activities. The goal of the present study was to evaluate the therapeutic potential of OA against acute and chronic brain injuries after ischemic stroke using a mouse model of transient middle cerebral artery occlusion (tMCAO, MCAO/reperfusion). OA administration immediately after reperfusion significantly attenuated acute brain injuries including brain infarction, functional neurological deficits, and neuronal apoptosis. Moreover, delayed administration of OA (at 3 h after reperfusion) attenuated brain infarction and improved functional neurological deficits during the acute phase. Such neuroprotective effects were associated with attenuation of microglial activation and lipid peroxidation in the injured brain after the tMCAO challenge. OA also attenuated NLRP3 inflammasome activation in activated microglia during the acute phase. In addition, daily administration of OA for 7 days starting from either immediately after reperfusion or 1 day after reperfusion significantly improved functional neurological deficits and attenuated brain tissue loss up to 21 days after the tMCAO challenge; these findings supported therapeutic effects of OA against ischemic stroke-induced chronic brain injury. Together, these findings showed that OA exerted neuroprotective effects against both acute and chronic brain injuries after tMCAO challenge, suggesting that OA is a potential therapeutic agent to treat ischemic stroke.

• The Journal of Korean Physical Therapy
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• 제15권4호
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• pp.199-207
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• 2003

신생아의 정상적인 발달을 저해하고 조기 사망의 주된 원인이 되고 있는 주산기 뇌손상에 관한 신경병리적 기전을 살펴보고자 하였다. 발달하고 있는 과정에서의 주산기 뇌손상은 주로 저산소성-허혈성 뇌손상과 출혈성 뇌손상에 의한 경우가 많다. 저산소성-허혈성 뇌손상과 관련하여 에너지 부전, 세포흥분독성, 미성숙 백질의 선택적 취약성을 고려해 볼 수 있다. 첫번째, 세포호흡에 관여하는 미토콘드리아의 손상과 관련하여 즉각적인 병리와 함께 지연된 양상의 손상을 보인다. 미토콘드리아의 호흡률이 감소하고 칼슘이온의 농도가 상승하여 세포 괴사 및 세포사멸 과정이 진행된다. 두번째, 흥분성 아미노산과 관련하여 미성숙한 뇌에는 NMDA 수용기-채널 복합체의 기능이 매우 풍부하고, phosphoinositide 가수분해가 높아서 흥분독성에 상당히 취약하다. 세 번째, 수초 형성에 중요한 역할을 하는 희돌기교세포가 주산기 뇌손상 특히, 저산소성-허혈성 손상에 취약하다. 희돌기교세포는 글루타메이트에 의한 자유유리기과 사이토카인 손상에 취약하다. 뇌출혈과 관련하여, 미성숙한 뇌는 뇌실 주위에 혈관층이 풍부하나 매우 약한 상태로 재관류 혹은 혈류의 증가로 인해 쉽게 파열된다. 특히 32주 이내인 경우 이러한 손상으로 인해 뇌실주위 백질연화증이 초래된다.

• 대한핵의학회지
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• 제35권6호
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• pp.343-351
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• 2001

Cerebral post-ischemic hyperperfusion has been observed at the acute and subacute periods of ischemic stroke. In the animal stroke model, early post-ischemic hyperperfusion is the mark of recanalization of the occluded artery with reperfusion. In the PET studios of both humans and experimental animals, early post-ischemic hyperperfusion is not a key factor in the development of tissue infarction and indicates the spontaneous reperfusion of the ischemic brain tissue without late infarction or with small infarction. But late post-ischemic hyperperfusion shows the worse prognosis with reperfusion injury associated with brain tissue necrosis. Early post-ischemic hyperperfusion defined by PET and SPECT may be useful in predicting the prognosis of ischemic stroke and the effect of thrombolytic therapy.

• 동의신경정신과학회지
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• 제17권3호
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• pp.45-56
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• 2006

Objective: Yukmijibwang-Tang(UJT) has been used for Dementia derived by deficiency of Kidney-Yin in the oriental medicine. This study was planned to examine the effects of UJT on the memory loss induced by focal brain ischemic injury in the rats. Methods : Experimental groups were divided into 4 groups ; Normal group, Control group, UJT1 group and UJT2 group. Control group were no treated after focal brain ischemic injury. UJT1 group were administered UJT 0.3 $m{\ell}/kg$ to focal brain ischemic injuried rats for 21 days, UJT2 group were administered UJT 1.2 $m{\ell}/kg$ to focal brain ischemic injuried rats for 21 days. The present author observed the number of errors on the eight-arm radial maze task, the rate of correct choice on the eight-arm radial maze task, the values of density of Cresy1 violet- stained sections in the hippocampal CA1 and the values of density of Acetlycholine Esterase (AchE)stained nuclei in the hippocampal CA1. Results : The number of errors in the Eigth-arm radial maze task was significantly decreased in UJT1 group on 1, 2, 3, 5, 6days, And it was significantly decreased in UJT2 group on 1-6days compared with control group. The rate of correct choice in the eight-arm radial maze task was significantly increased in UJT1, UJT2 group compared with control group. The values of density of Cresyl violet-stained stained sections in the hippocampal CA1 were significantly increased in UJT1, UJT2 group compared with control group. The values of density of AchE in the hippocampal CA1 were increased in UJT1, UJT2 group compared with control group, but the values were not significant. Conclusions: The present author thought that Yukmijihwang-Tang could he used for curing dementia induced by focal brain ischemic injury.

• 약학회지
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• 제44권4호
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• pp.371-377
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• 2000

In order to investigate the pharmacological properties of fractions of Astragali Radix and Polygalae Radix, the effects of the fractions on cerebral ischemia and subsequent reperfusion were studied. Brain ischemia was induced by bilateral common carotid artery occlusion in mongolian gerbil. Brains were recirculated for 30 mins after the 20 min occlusion. Methanol and butanol fractions of Astragali Radix and Polygalae Radix were administered orally 2 hrs before common carotid artery occlusion. Histological observations showed that brain ischemia induced severe brain damage evidenced by the presence of necrotic foci, edema and hemorrhage. This injury was prevented by the methanol fraction and butanol fraction of Polygalae Radix. The level of ATP in brain tissue significantly decreased in ischemic gerbils. This decrease was prevented by the pretreatment with butanol fraction of Polygalae Radix. In contrast, the levels of lactate and lipid peroxide were both elevated in ischemic gerbils. This elevation was inhibited by the pretreatments with methanol fraction and butanol fraction of Polygalae Radix. Our findings suggest that the Polygalae Radix improves ischemia-induced brain damage.

• Clinical and Experimental Pediatrics
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• 제52권1호
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• pp.105-110
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• 2009

목적 : 신생 백서의 저산소 허혈 뇌손상에 있어서의 erythropietin (Epo) 투여의 손상 예방 효과와 보호 기전에 철 대사가 관여하는지를 조사하고자 하였다. 방 법 : 신생 백서를 암수 구별 없이 생후 7일째에 편측 온목동맥 결찰 후 산소 농도 8%인 환경에 2시간 노출시켜 저산소 허혈을 유도하였으며 저산소 노출 직후 Epo 5,000 u/kg를 복강내 투여하였다. 이들은 저산소 허혈 유도 전 투여한 생리식염수, 철, deferoxamine 등에 따라 Epo군, Iron+Epo군, Def+Epo군, Iron+ Def+Epo군, 대조군으로 나누어 저산소 허혈 유도 후 7일에 뇌손상 정도를 비교하였다. 결 과 : Epo 투여시 뇌손상의 빈도와 정도는 대조군에 비해 감소하였다. 뇌손상의 빈도와 손상 점수로 뇌손상 정도를 비교한 결과 철 투여는 Epo의 뇌손상 예방 효과를 감소시키지 않았다. Deferoxamine 투여는 Epo 단독 투여군에 비해 뇌손상의 빈도와 정도가 경감하였으나 통계적 유의성은 없었다. 결 론 : Epo는 저산소 허혈 뇌손상에 있어 뇌손상 보호 효과를 보인다. 철 투여는 뇌손상을 악화시키지 않았으나 deferoxamine 동시 투여는 Epo 단독 투여에 비해 뇌손상의 빈도와 손상 점수가 감소하여 뇌손상 보호 효과에 철 대사가 관여할 가능성을 제시하였다.

• 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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• 제23권6호
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• pp.531-538
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• 2015

Preceding infection or inflammation such as bacterial meningitis has been associated with poor outcomes after stroke. Previously, we reported that intracorpus callosum microinjection of lipopolysaccharides (LPS) strongly accelerated the ischemia/reperfusionevoked brain tissue damage via recruiting inflammatory cells into the ischemic lesion. Simvastatin, 3-hydroxy-3-methylgultaryl (HMG)-CoA reductase inhibitor, has been shown to reduce inflammatory responses in vascular diseases. Thus, we investigated whether simvastatin could reduce the LPS-accelerated ischemic injury. Simvastatin (20 mg/kg) was orally administered to rats prior to cerebral ischemic insults (4 times at 72, 48, 25, and 1-h pre-ischemia). LPS was microinjected into rat corpus callosum 1 day before the ischemic injury. Treatment of simvastatin reduced the LPS-accelerated infarct size by 73%, and decreased the ischemia/reperfusion-induced expressions of pro-inflammatory mediators such as iNOS, COX-2 and IL-$1{\beta}$ in LPS-injected rat brains. However, simvastatin did not reduce the infiltration of microglial/macrophageal cells into the LPS-pretreated brain lesion. In vitro migration assay also showed that simvastatin did not inhibit the monocyte chemoattractant protein-1-evoked migration of microglial/macrophageal cells. Instead, simvastatin inhibited the nuclear translocation of NF-${\kappa}B$, a key signaling event in expressions of various proinflammatory mediators, by decreasing the degradation of $I{\kappa}B$. The present results indicate that simvastatin may be beneficial particularly to the accelerated cerebral ischemic injury under inflammatory or infectious conditions.

• Biomolecules & Therapeutics
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• 제8권2호
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• pp.160-166
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• 2000

The present study examined influence of various ischemic duration on extent of focal ischemic brain injury induced by middle cerebral artery occlusion (MCAO) in rats. The MCAO was produced by insertion of a 17 mm silicone-coated 4-0 nylon surgical thread to the origin of MCA through the internal carotid artery for 30, 60, 90, 120 min (transient) or 24 hr (permanent) in male Sprague-Dawley rats under isoflurane anesthesia. Reperfusion in transient MCAO models was achieved by pulling the thread out of the internal carotid artery. Only rats showing neurological deficits characterized by left hemiparesis and/or circling to the left, were included in cerebral ischemic groups. The rats were sacrificed 24 hr after MCAO and seven serial coronal slices of the brain were stained with 2,3,5-triphenyltetrazolium chloride. Infarct size was measured using a computerized image analyzer. Ischemic damage was common in the frontoparietal cortex (somatosensory area) and the lateral segment of the striatum while damage to the medial segment of the striatum depended on the duration of the occlusion. In the 30-min MCAO grouts, however, infarcted region was primarily confined to the striatum and it was difficult to clearly delineate the region since there was mixed population of live and dead cells in the nucleus. Infarct volume was generally increased depending on the duration of MCAO, showing the most severe damage in the permanent MCAO group. However, there was no significant difference in infarct size between the 90-min and 120-min MCAO groups. % Edema also tended to increase depending on the duration of MCAO. The results suggest that the various focal ischemic rat models established in the present study can be used to evaluate in vivo neuroprotective activities of candidate compounds or to elucidate pathophysiological mechanisms of ischemic neuronal cell death.