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The role of cytokines in seizures: interleukin (IL)-$1{\beta}$, IL-1Ra, IL-8, and IL-10

  • Youn, Youngah;Sung, In Kyung;Lee, In Goo
    • Clinical and Experimental Pediatrics
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    • v.56 no.7
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    • pp.271-274
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    • 2013
  • Brain insults, including neurotrauma, infection, and perinatal injuries such as hypoxic ischemic encephalopathy, generate inflammation in the brain. These inflammatory cascades induce a wide spectrum of cytokines, which can cause neuron degeneration, have neurotoxic effects on brain tissue, and lead to the development of seizures, even if they are subclinical and occur at birth. Cytokines are secreted by the glial cells of the central nervous system and they function as immune system mediators. Cytokines can be proinflammatory or anti-inflammatory. Interleukin (IL)-$1{\beta}$ and IL-8 are proinflammatory cytokines that activate additional cytokine cascades and increase seizure susceptibility and organ damage, whereas IL-1 receptor antagonist and IL-10 act as anti-inflammatory cytokines that have protective and anticonvulsant effects. Therefore, the immune system and its associated inflammatory reactions appear to play an important role in brain damage. Whether cytokine release is relevant for the processes of epileptogenesis and antiepileptogenesis, and whether epileptogenesis could be prevented by immunomodulatory treatment should be addressed in future clinical studies. Furthermore, early detection of brain damage and early intervention are essential for the prevention of disease progression and further neurological complications. Therefore, cytokines might be useful as biomarkers for earlier detection of brain damage in high-risk infants.

MR Images of Spontaneously Involuted Atretic Cephalocele Concomitant with Persistent Falcine Sinus in an Adult (성인에서 지속적인 낫형동을 동반한 자연퇴축된 위축뇌탈출증의 MR영상소견)

  • Cho, Joon;Roh, Hong-Gee;Moon, Won-Jin;Kim, Mi-Young
    • Investigative Magnetic Resonance Imaging
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    • v.10 no.2
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    • pp.117-120
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    • 2006
  • Atretic cephalocelces are defined as skin-covered midline subscalp lesions that contain meninges and rest of glial and/or central nervous system tissue. When the straight sinus is absent or rudimentary, the falcine sinus can be recanalized to enable venous drainage. Although the atretic cephalocele or persistent falcine sinus has largely been described in the pediatric population, it is a rarely observed in the adult population. We report a unique case of spontaneously involuted atretic cephalocele coexistent with persistent falcine sinus in an adult. MR images and MR venography were useful for diagnosis and accurate anatomical depiction.

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Animal Models for Aging and Neurodegenerative Diseases: Brain Cell Apoptosis in the Dog and its Possible Mechanisms

  • Nakayama, Hiroyuki;Kajikawa, Satoru;Doi, Kunio
    • Toxicological Research
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    • v.17
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    • pp.71-77
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    • 2001
  • The brain of the aged dog possesses senile plaques and amyloid angiopathy, which characterize Alzheimer's disease brains. We have defined the dementia condition of aged dogs and examined which mechanism(s) is responsible for the condition. A series of studies revealed that the dementia condition in aged dogs is significantly related to the number of apoptotic brain cells including both neurons and glial cells, but not to the number of senile plaques. On the other hand, 5-azacytidine (5AzC) is a cytidine analogue, and is thought to induce kinds of cell differentiation possibly through hypomethylation of genomic DNA. We have revealed neuronal apoptosis induced in 5AzC-treated fetal mice and PC12 cells. The ribosomal protein L4 (rpL4) gene is expressed prior to the apoptosis in the PC12 cell system. Therefore, the involvement of the rpL4 gene expression in age-related brain cell apoptosis in dogs may contribute to the investigation of Alzheimer's dementia.

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A Case of Desmoplastic Infantile Ganglioglioma (결합조직형성성 영아 신경절교종)

  • Song, Kwang-Chul;Kim, Seong-Ho;Bae, Jang-Ho;Kim, Oh-Lyong;Choi, Byung-Yon;Cho, Soo-Ho;Kim, Dong-Seok
    • Journal of Yeungnam Medical Science
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    • v.14 no.2
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    • pp.451-458
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    • 1997
  • The desmoplastic infantile ganglioglioma is very rare cerebral tumor. It has been known to be characterized by its voluminious size, intense desmoplasia and the frequent presence of astrocytic and ganglioglionic differentiation. Also, It is usually presented in infantile period and predilected in the frontal and parietal lobes. We treated a huge desmoplastic infantile ganglioglioma($8{\times}7{\times}6cm$) on the right frontotemporo-parietal areas of with only gross total resection. It includes solid mass & several cysts and shows the areas of the proliferation of spindle cells exhibiting storiform pattern in dense desmoplastic stroma and the areas composed of spindle shaped glial component.

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Influence of Aspirin on Pilocarpine-Induced Epilepsy in Mice

  • Jeong, Kyoung Hoon;Kim, Joo Youn;Choi, Yun-Sik;Lee, Mun-Yong;Kim, Seong Yun
    • The Korean Journal of Physiology and Pharmacology
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    • v.17 no.1
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    • pp.15-21
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    • 2013
  • Aspirin (acetylsalicylic acid) is one of the most widely used therapeutic agents based on its pharmacological actions, including anti-inflammatory, analgesic, anti-pyretic, and anti-thrombotic effects. In this study, we investigated the effects of aspirin on seizure susceptibility and hippocampal neuropathology following pilocarpine-induced status epilepticus (SE). SE was induced by pilocarpine hydrochloride (280 mg/kg, i.p.) administration in C57BL/6 mice (aged 8 weeks). Aspirin was administered daily (15 mg/kg or 150 mg/kg, i.p.) for 10 days starting 3 days before SE, continuing until 6 days after SE. After pilocarpine injection, SE onset time and mortality were recorded. Neuronal cell death was examined using cresyl violet and Fluoro-Jade staining, and glial responses were observed 7 days post SE using immunohistochemistry. In the aspirin-treated group, the onset time of SE was significantly shortened and mortality was markedly increased compared to the control group. However, in this study, aspirin treatment did not affect SE-induced neuronal cell death or astroglial and microglial responses in the hippocampus. In conclusion, these results suggest that the safety of aspirin should be reevaluated in some patients, especially with neurological disorders such as temporal lobe epilepsy.

Effect of glucose level on chemical hypoxia- and hydrogen peroxide-induced chemokine expression in human glioblastoma cell lines

  • Jung, Yieun;Ahn, So-Hee;Park, Sang Hui;Choi, Youn-Hee
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.5
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    • pp.509-518
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    • 2017
  • Glioblastoma multiforme (GBM) is the most common primary intracranial tumor in adults and has poor prognosis. The GBM-specific tumor microenvironment (TME) plays a crucial role in tumor progression, immune escape, local invasion, and metastasis of GBM. Here, we demonstrate that hypoxia, reactive oxygen species (ROS), and differential concentration of glucose influence the expression of cytokines and chemokines, such as IL-6, IL-8, and IP-10, in human glial cell lines. Treatment with cobalt chloride ($CoCl_2$) and hydrogen peroxide ($H_2O_2$) significantly increased the expression levels of IL-6, IL-8, and IP-10 in a dose-dependent manner in CRT-MG and U251-MG astroglioma cells, but not in microglia cells. However, we found strikingly different patterns of expression of cytokines and chemokines between $H_2O_2$-treated CRT-MG cells cultured in low- and high-glucose medium. These results suggest that astroglioma and microglia cells exhibit distinct patterns of cytokine and chemokine expression in response to $CoCl_2$ and $H_2O_2$ treatment, and different concentrations of glucose influence this expression under either hypoxic or oxidant-enriched conditions.

Phenytoin Induced Erythema Multiforme after Cranial Radiation Therapy

  • Kazanci, Atilla;Tekkok, Ismail Hakki
    • Journal of Korean Neurosurgical Society
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    • v.58 no.2
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    • pp.163-166
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    • 2015
  • The prophylactic use of phenytoin during and after brain surgery and cranial irradiation is a common measure in brain tumor therapy. Phenytoin has been associated with variety of adverse skin reactions including urticaria, erythroderma, erythema multiforme (EM), Stevens-Johnson syndrome, and toxic epidermal necrolysis. EM associated with phenytoin and cranial radiation therapy (EMPACT) is a rare specific entity among patients with brain tumors receiving radiation therapy while on prophylactic anti-convulsive therapy. Herein we report a 41-year-old female patient with left temporal glial tumor who underwent surgery and then received whole brain radiation therapy and chemotherapy. After 24 days of continous prophylactic phenytoin therapy the patient developed minor skin reactions and 2 days later the patient returned with generalized erythamatous and itchy maculopapuler rash involving neck, chest, face, trunk, extremities. There was significant periorbital and perioral edema. Painful mucosal lesions consisting of oral and platal erosions also occurred and prevented oral intake significantly. Phenytoin was discontinued gradually. Systemic admistration of corticosteroids combined with topical usage of steroids for oral lesions resulted in complete resolution of eruptions in 3 weeks. All cutaneous lesions in patients with phenytoin usage with the radiotherapy must be evoluated with suspicion for EM.

Isolation of a Hypoxia/Reoxygenation Regulatory Factor in Rat Astrocytes (흰쥐 성상세포에서 산소농도의존성 유전자의 분리)

  • Park Jeong-Ae;Song Hyun-Seok;Lee Hye-Shin;Kim Kyu-Won
    • YAKHAK HOEJI
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    • v.50 no.2
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    • pp.124-128
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    • 2006
  • Astrocyte has emerged as an active regulator of brain function, which connects between blood vessels and neurons as well as is a structural component of the blood-brain barrier, From its structural characteristics, astrocyte seems to sensitively respond to oxygen tension, and, in turn, generate diverse cellular cascades. Therefore, to reveal astrocytlc events by oxygen change, we screened genes whose expressions are upregulated under reoxygenation after hypoxic stress using cDNA representational difference analysis (RDA) technique. Meteorin that regulates glial differentiation was isolated from primary cultured rat astrocytes as a hypoxia/reoxygenation regulatory factor. We cloned rat version of Meteorin (rMe-teorin) and determined full-size sequences of rMeteorin. In addition, RT-PCR analysis revealed that Meteorin was increased under reoxygenation in astrocytes and highly expressed in the developing brain. Collectively, these results suggest that Meteorin may regulate astrocyte-mediated effects in response to the change of oxygen tension in the pathophysiological states.

Chongmyungtang Attenuates Kainic Acid-induced Seizure and Mortal Effect in the Mouse

  • Jang, Kyung-Jin;Lee, Kyou-Heung;Kim, Sang-Lin;Park, Dong-Young;Park, Beom-Kyu;Im, Doo-Hyung;Cho, Yong-Joon;Jhoo, Wang-Kee;Kim, Hyoung-Chun
    • Archives of Pharmacal Research
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    • v.20 no.4
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    • pp.375-378
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    • 1997
  • The Chongmyungtang (CMT; the combination of Acorus gramineus, polygala tenuifolia and Poria cocos) has been recognized to possess the preventive effect against several neurologic disorders in human. In this study, we examined the effect of CMT on the three parameters associated with kainic acid (KA)-induced neurotoxicities; seizure/mortality, increased fos-related antigen (FRA) and glial fibrillary acidic protein (GFAP) expression. KA induced vigorous convulsions lasting 4-6 hr. Pretreatments with CMT before KA injection significantly reduced the seizure intensity as well as the mortality. CMT pretreatments also attenuated the KA-induced increase in FRA/GFAP expression in the hippocampus. These results suggest that CMT has a neuroprotective effect against KA-induced neurotoxicities.

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Influence of Molarless Condition on the Hippocampal Formation in Mouse: a Histological Study (구치부 치관삭제가 생쥐 해마복합체에 미치는 영향에 관한 조직학적 연구)

  • Kim, Yong-Chul;Kang, Dong-Wan
    • Journal of Dental Rehabilitation and Applied Science
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    • v.23 no.2
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    • pp.179-186
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    • 2007
  • The decrease of masticatory function caused by tooth loss leads to a decrease of cerebral blood flow volume resulting in impairment of cognitive function and learning memory disorder. However, the reduced mastication-mediated morphological alteration in the central nervous system (CNS) responsible for senile deficit of cognition, learning and memory has not been well documented. In this study, the effect of the loss of the molar teeth (molarless condition) on the hippocampal expression of glial fibrillary acidic protein (GFAP) protein was studied by immunohistochemical techniques. The results were as follows : 1. The molarless mice showed a lower density of pyramidal cells in the cornu ammonis 1 (CA1) and dentate gyrus (DG) region of the hippocampus than control mice. 2. Immunohistochemical analysis showed that the molarless condition enhanced the time-dependent increase in the cell density and hypertrophy of GFAP immunoreactivity in the CA1 region of the hippocampus. The molarless condition enhanced an time-dependent decrease in the number of neurons in the hippocampal formation and the time-dependent increase in the number and hypertrophy of GFAP-labeled cells in the same region. The data suggest a possible link between reduced mastication and histological changes in hippocampal formation that may be one risk factor for senile impairment of cognitive function and spatial learning memory.