• International Journal of Oral Biology
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• 제40권2호
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• pp.71-77
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• 2015

The activation of glial cells in the spinal cord has been contribute to the initiation and maintenance of pain facilitation induced by peripheral inflammation and nerve injury. The present study investigated effects of botulinum toxin type A (BoNT-A), injected subcutaneously or intracisternally, on the expression of microglia and astrocytes in rats. Complete Freund's Adjuvant (CFA)-induced inflammation was employed as an orofacial chronic inflammatory pain model. A subcutaneous injection of $40{\mu}L$ CFA into the vibrissa pad was performed under 3% isoflurane anesthesia in SD rats. Immunohistochemical analysis for changes in Iba1 (a microglia marker) and GFAP (an astrocyte marker), were performed 5 days after CFA injection. Subcutaneous injection of CFA produced increases in Iba1 and GFAP expression, in the ipsilateral superficial lamia I and II in the medullary dorsal horn of rats. Subcutaneous treatment with BoNT-A attenuated the up-regulation of Iba1 and GFAP expressions induced by CFA injection. Moreover, intracisternal injection of BoNT-A also attenuated the up-regulated Iba1 and GFAP expressions. These results suggest that the anti-nociceptive action of BoNT-A is mediated by modulation activation of glial cells, including microglia and astrocyte.

• Clinical Psychopharmacology and Neuroscience
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• 제16권4호
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• pp.422-433
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• 2018

Objective: Neuropsychiatric manifestations like depression and cognitive dysfunction commonly occur in inflammatory bowel disease (IBD). In the context of the brain-gut axis model, colitis can lead to alteration of brain function in a bottom-up manner. Here, the changes in the response of the hypothalamic-pituitary-adrenal axis and inflammation-related markers in the brain in colitis were studied. Methods: Dextran sodium sulfate (DSS) was used to generate a mouse model of colitis. Mice were treated with DSS for 3 or 7 days and sacrificed. We analyzed the gene expression of brain-derived neurotrophic factor (BDNF), cyclooxygenase 2 (COX-2), and glial fibrillary acidic protein (GFAP), and the expression of GFAP, in the hippocampus, hypothalamus, and amygdala. Additionally, the levels of C-reactive protein (CRP) and serum cortisol/corticosterone were measured. Results: Alteration of inflammatory-related markers varied depending on the brain region and exposure time. In the hippocampus, COX-2 mRNA, GFAP mRNA, and GFAP expression were upregulated during exposure to DSS. However, in the hypothalamus, COX-2 mRNA was upregulated only 3 days after treatment. In the amygdala, BDNF and COX-2 mRNAs were downregulated. CRP and corticosterone expression increased with DSS treatment at day 7. Conclusion: IBD could lead to neuroinflammation in a bottom-up manner, and this effect varied according to brain region. Stress-related hormones and serum inflammatory markers, such as CRP, were upregulated from the third day of DSS treatment. Therefore, early and active intervention is required to prevent psychological and behavioral changes caused by IBD, and region-specific studies can help understand the precise mechanisms by which IBD affects the brain.

• 대한본초학회지
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• 제29권5호
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• pp.23-30
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• 2014

Objectives : Dodam-tang has been reported to have a control effect against the hyperlipidemia and thrombosis. Based upon these previous reports, this study investigates the effects of Dodam-tang on the cerebral ischemic damage of the hyperlipidemic rats. Methods : Hyperlipidemia was induced by the beef tallow 30% diet for 14 days on Sprague-Dawley rats. Ischemic damage was induced by the middle cerebral artery occlusion (MCAO) for 2 hours with the intraluminal thread method. Then water extract of Dodam-tang was administered daily for 5 days. The effect of Dodam-tang was evaluated with the serum lipids, infarct volume and edema percentage, and immunohistochemical expressions of iNOS, MMP-9, and GFAP in the brain tissue. Results : The obtained results were as follows; Dodam-tang reduced significantly the infarct size in a TTC-stained 5th brain section of the hyperlipidemic MCAO rats. Dodam-tang suppressed the infarct volume of the hyperlipidemic MCAO rats, but not significant statistically. Dodam-tang suppressed the edema percentage of the hyperlipidemic MCAO rats significantly in the brain tissue. Dodam-tang suppressed significantly the iNOS expression in the cerebral penumbra and caudate putamen of the hyperlipidemic MCAO rats. Dodam-tang suppressed significantly the MMP-9 expression in the cerebral penumbra of the hyperlipidemic MCAO rats. Dodam-tang suppressed significantly the GFAP-expressed atrocytes in the cerebral penumbra of the hyperlipidemic MCAO rats. Conclusions : These results suggest that Dodam-tang suppresses the brain edema formation through the suppression of the iNOS, MMP-9 and GFAP, but the neuroprotective effect against the cerebral infarct are not distinct.

• 구강회복응용과학지
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• 제23권2호
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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.

• 동의신경정신과학회지
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• 제20권2호
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• pp.31-46
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• 2009

Objectives : This experiment was designed to investigate the effect of Gojineumja(Guzhenyinzi, GJEJ) on damaged neural tissue in cultured glial cells and in the mouse brain tissue. Methods : The effects of the GJEJ on activation of astrocytes and caspase 3-positive cell counts in cultured glial cells administered with ${\beta}$-amyloid peptide were investigated. The effects of the GJEJ on levels of glial fibrillary acidic protein(GFAP)-positive reactive astrocyets and caspase 3-positive cells in the hippocampal subfields in the rats administered with scopolamine were investigated. Results : 1. GJEJ reduced levels of activated astrocytes and caspase 3-positive cell counts in cultured glial cells administered with ${\beta}$-amyloid peptide. 2. GJEJ reduced levels of GFAP-positive reactive astrocyets and caspase 3-positive cells in the hippocampal subfields in the rats administered with scopolamine. Conclusions : The present data. suggest that GJEJ may have a protective function of neuronal and non-neuronal cells in damaged neural tissue caused by AD-like stimulations. Further studies on identification of effective molecular components of GJEJ and their interactions with damaged neural cells would be important for understanding molecular mechanism and may be further applicable for the development of therapeutic strategies.

• 동의생리병리학회지
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• 제22권2호
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• pp.321-327
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• 2008

This study evaluated neuroprotective effects of Yanggyuksanhwa-tang (YST) on global cerebral ischemia of diabetic rats. On primary experiment, diabetic condition in rats was induced by streptozotocin injection. Secondarily, global cerebral ischemia was induced by bilateral occlusion of the common carotid artery with hypotension (BCAO) under the diabetic condition. Then neuroprotective effect of YST was observed with changes of neuronal c-Fos and Bax expressions, and GFAP expression in the brain tissues by using immunohistochemistry. YST treatment was resulted significant decrease of c-Fos expression in CA1 hippocampus induced by BCAO on diabetic rats. YST treatment was resulted significant decrease of Bax expression in CA1 hippocampus induced by BCAO on diabetic rats. YST treatment was resulted significant decrease of c-Fos expression in cerebral cortex and caudoputamen induced by BCAO on diabetic rats. YST treatment was resulted significant decrease of GFAP expression in cerebral cortex induced by BCAO on diabetic rats. These results suggest that YST has effects on neuroprotection against cerebral ischemic damage under diabetic condition. And it is supposed that neuroprotective effect of YST reveals by anti-apoptosis mechanism.

• 생명과학회지
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• 제26권12호
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• pp.1355-1359
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• 2016

인간 중간엽 줄기세포(hMSCs)는 신경세포(neuron-like cells)를 포함한 다양한 세포로 분화할 수 있는 능력을 지닌 성체 줄기세포(adult stem cells)이다. 본 연구에서는 인간의 골수유래-중간엽 줄기세포(bone marrow-mesenchymal stem cells; hBM-MSCs)를 이용한 신경분화에서 신경세포 표지자(neuronal marker)인 NF-M, Tuj-1 뿐만 아니라 성상세포 표지자(glial marker)인 GFAP의 발현 역시 의미 있게 증가함을 real-time PCR, Western blot, and immunocytochemical staining법을 통하여 관찰하였다. 이를 개선하기 위하여, 신경분화에 중요한 신호전달자(signal intermediator)인 PDE4를 억제한 후 신경분화를 유도하였다. PDE4 억제자인 rolipram 혹은 resveratrol를 각각 처리하여 신경분화한 줄기세포(Roli- or RSV-dMSCs)에서 NF-M, Tuj-1의 발현이 증가하였고 반면, GFAP의 발현은 감소함을 real-time PCR, Western blot, and immunocytochemical staining법을 통하여 관찰하였다. 본 연구를 통하여, PDE4를 조절하며 줄기세포의 신경분화를 개선할 수 있음을 보였다.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Signal transduction in Toxicology
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• pp.123-123
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• 2001

The distribution of necrotic and apoptotic neural cells, and expression of astrocytic glial fibrillary acidic protein (GFAP) in the brain of rats poisoned intraperitoneally with diisopropylfluorophosphate were investigated. Pyridostigmine bromide (0.1 mg/kg) and atropine methylnitrate (20 mg/kg), which are centrally inactive, were treated intramuscularly 30 min and 10 min, respectively, before diisopropylfluorophosphate (4 - 10 mg/kg) poisoning to reduce the mortality.(omitted)

• 대한약리학회지
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• 제30권2호
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• pp.167-179
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• 1994

Recent evidence indicates that glial cells have a wide range of funtions which are critical for maintaining a balanced homeostatic environment in the central nervous system(CNS) peripheral nervous system(PNS). Morever, astrocytes are known to participate in the tissue repair and neuroimmunologic events within the CNS through many kinds of growth factors and cytokines. We investigated the effect of $TGF\;{\beta}_1$, on the growth and biochemical changes of rat glial cells in culture. The proliferative effect was determined by $^3H-thymidine$ uptake and the double immunostain with anti-cell-specific marker and anti-Bromodeoxyuridine(BrdU) antibody. To check the effect of biochemical changes we compared the amounts of glial fibrillar acidic protein(GFAP) and the activity of glutamine synthetase(GS) in astrocyte. And the amounts of myelin basic protein and the activity of 2',3'-cyclic nucleotide phosphohydrolase(CNPase) were measured in oligodendrocyte and the amounts of peripheral myelin in Schwann cell. When $TGF\;{\beta}_1$, was treated for 2 days with cultured glial cell, $TGF\;{\beta}_1$, decreased the $^3H-thymidine$ uptake and proliferation index of double immunostain of astrocytes, which indicates the inhibition of astroglial DNA synthesis, but stimulated the growth of Schwann cell. Also, $TGF\;{\beta}_1$, decrease the GS activity and increased the amounts of GFAP in astrocyte. In the case of Schwann cells the amounts of peripheral myelin was increased when treated with $TGF\;{\beta}_1$. However, $TGF\;{\beta}_1$, didn't show any effect on the proliferation and biochemical changes in oligodendrocyte. These results suggest that $TGF\;{\beta}_1$, might have a critical action in the regulation of proliferation and biochemical changes in glial cells, especially astrocyte.

• Journal of Korean Neurosurgical Society
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• 제30권8호
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• pp.963-969
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• 2001

Objectives : Cord blood stem cells have been widely used as donor cells for bone marrow transplantation recently. These cells can give rise to a variety of hematopoietic lineages to repopulate the blood. Recent observations reveal that some bone marrow cells and bone marrow stromal cells(MSCs) can grow to become either neurons or glial cells. It is, however, unclear whether or not there exists stems cells which can differentiate into neurons in the blood during the early stages of postnatal life. Methods : Human cord blood stem cells were prepared from human placenta after full term delivery. To induce neuronal differentiation of stem cells, ${\beta}$-mercaptoethanol was treated. To confirm the neuro-glial characteristics of differentiated stem cells, immunocytochemical stain for NeuN, neurofilament, glial fibrillary acidic protein(GFAP), microtubule associated protein2(MAP2) was performed. RT-PCR was performed for detecting nestin mRNA and MAP2 mRNA. Results : We showed in this experiment that neuro-glial markers(NeuN, neurofilament, MAP2, GFAP) were expressed and axon-like cytoplasmic processes are elaborated in the cultured human cord blood stem cells prepared from new born placenta after full term delivery. Nestin mRNA was also detected in fresh cord blood monocytes. Conclusions : These results suggest that human cord blood derived stem cells may be potential sources of neurons in early postnatal life.