• Title, Summary, Keyword: Microglial activation

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EFFECTS OF MANDIBULAR NERVE TRANSECTION ON TRIGEMINAL GANGLION NEURONS AND THE ACTIVATION OF MICROGLIAL CELLS IN THE MEDULLARY DORSAL HORN (하악신경 절삭이 삼차신경절 신경세포와 연수후각 소교세포 활성화에 미치는 영향)

  • Lim, Yo-Han;Choie, Mok-Kyun
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.33 no.3
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    • pp.227-237
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    • 2007
  • Microglial cell activation is known to contribute to neuropathic pain following spinal sensory nerve injuries. In this study, I investigated its mechanisms in the case of trigeminal sensory nerve injuries by which microglial cell and p38 mitogen-activated protein kinase (p38 MAPK) activation in the medullary dorsal horn (MDH) would contribute to the facial pain hypersensitivity following mandibular nerve transection (MNT). And also investigated the changes of trigeminal ganglion neurons and ERK, p38 MAPK manifestations. Activation of microglial cells was monitored at 1, 3, 7, 14, 28 and 60 day using immunohistochemical analyses. Microglial cell activation was primarily observed in the superficial laminae of the MDH. Microglial cell activation was initiated at postoperative 1 day, maximal at 3 day, maintained until 14 day and gradually reduced and returned to the basal level by 60 days after MNT. Pain hypersensitivity was also initiated and attenuated almost in parallel with microglial cell activation pattern. To investigate the contribution of the microglial cell activation to the pain hypersensitivity, minocycline, an inhibitor of microglial cell activation by means of p38 MAPK inhibition, was administered. Minocycline dose-dependently attenuated the development of the pain hypersensitivity in parallel with inhibition of microglial cell and p38 MAPK activation following MNT. Mandibular nerve transection induced the activation of ERK, but did not p38 MAPK in the trigeminal ganglion. These results suggest that microglial cell activation in the MDH and p38 MAPK activation in the hyperactive microglial cells play an important role in the development of facial neuropathic pain following MNT. The results also suggest that ERK activation in the trigeminal ganglion contributes microglial cell activation and facial neuropathic pain.

Schizandra chinensis Alkaloids Inhibit Lipopolysaccharide-Induced Inflammatory Responses in BV2 Microglial Cells

  • Choi, Min-Sik;Kwon, Kyung-Ja;Jeon, Se-Jin;Go, Hyo-Sang;Kim, Ki-Chan;Ryu, Jae-Ryun;Lee, Jong-Min;Han, Seol-Heui;Cheong, Jae-Hoon;Ryu, Jong-Hoon;Bae, Ki-Hwan;Shin, Chan-Young;Ko, Kwang-Ho
    • Biomolecules & Therapeutics
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    • v.17 no.1
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    • pp.47-56
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    • 2009
  • Schizandra chinensis (S. chinensis) exhibits a harmless, 'adaptogen-type' effect leading to improvements in mental performance and learning efficacy in brain. Activated microglia contributes to neuronal injury by releasing neurotoxic products, which make it important to regulate microglial activation to prevent further cytological as well as functional brain damage. However, the effect of S. chinensis on microglial activation has not been examined yet. We have investigated the effects of four compounds (Gomisin A, Gomisin N, Schizandrin and Schizandrol A) from S. chinensis on lipopolysaccharide (LPS)-induced microglial activation. In this study, BV2 microglial cells were activated with LPS and the microglial activation was assessed by up-regulation of activation markers such as nitric oxide (NO), reactive oxygen species (ROS), and matrix metalloproteinase-9 (MMP-9). The results showed that all four compounds significantly reduced the intracellular level of ROS, the release of NO and MMP-9 as well as LPS-induced phosphorylation of ERK1/2. These results strongly suggested that S. chinensis may be useful to modulate inflammation-mediated brain damage by regulating microglial activation.

Effects of Curcumin on the Microglial Activation (Curcumin이 microglia의 활성화에 미치는 영향)

  • 정기경;이상진;이선우;강석연;김태균;강주혜;홍성렬;주일로;김승희
    • YAKHAK HOEJI
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    • v.44 no.5
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    • pp.448-454
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    • 2000
  • Microglia, brain resident macrophages, play a central role in the inflammatory responses of the brain and are activated in brain injuries and several neurodegenerative diseases such as Alzheimer's and Parkinson's disease, thereby aggravating the course of these diseases. In this study, the effects of plantderived compounds such as curcumin or gingerol on the microglial activation were examined. Microglial cultures were prepared from 2~3 week mixed primary glial cultures obtained from the cerebral cortex of 1~2 day old rats and identified by immunocytochemistry using microglial-specific antibody OX-42. Microglia were activated by lipopolysaccharide (LPS) and interferon-${\gamma}$ (IFN-${\gamma}$) and the effect of curcumin or 6-gingerol on the microglial activation was examined. Specific parameters measured to monitor microglial activation were nitric oxide (NO), prostaglandin E$_2$(PGE$_2$) and tumor necrosis factor-$\alpha$ (TNF-$\alpha$) release. Curcumin (1~10 $\mu$M) inhibited NO release induced by LPS and IFN-${\gamma}$ in a dose-dependent manner whereas 6-gingerol (2~20 $\mu$M) did not have any effect on LPS/IFN-${\gamma}$-induced NO release. The levels of PGE$_2$and TNF-$\alpha$ induced by LPS and IFN-${\gamma}$ were also inhibited by 1~10 $\mu$M curcumin in a dose-dependent manner. These results showed that curcumin could modulate microglial activation.

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Antineuroinflammatory Effects of 7,3',4'-Trihydroxyisoflavone in Lipopolysaccharide-Stimulated BV2 Microglial Cells through MAPK and NF-κB Signaling Suppression

  • Kim, Seon-Kyung;Ko, Yong-Hyun;Lee, Youyoung;Lee, Seok-Yong;Jang, Choon-Gon
    • Biomolecules & Therapeutics
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    • v.29 no.2
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    • pp.127-134
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    • 2021
  • Neuroinflammation―a common pathological feature of neurodegenerative disorders such as Alzheimer's disease―is mediated by microglial activation. Thus, inhibiting microglial activation is vital for treating various neurological disorders. 7,3',4'-Trihydroxyisoflavone (THIF)―a secondary metabolite of the soybean compound daidzein―possesses antioxidant and anticancer properties. However, the effects of 7,3',4'-THIF on microglial activation have not been explored. In this study, antineuroinflammatory effects of 7,3',4'-THIF in lipopolysaccharide (LPS)-stimulated BV2 microglial cells were examined. 7,3',4'-THIF significantly suppressed the production of the proinflammatory mediators nitric oxide (NO), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) as well as of the proinflammatory cytokine interleukin-6 (IL-6) in LPS-stimulated BV2 microglial cells. Moreover, 7,3',4'-THIF markedly inhibited reactive oxygen species (ROS) generation. Western blotting revealed that 7,3',4'-THIF diminished LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), glycogen synthase kinase-3β (GSK-3β), and nuclear factor kappa B (NF-κB). Overall, 7,3',4'-THIF exerts antineuroinflammatory effects against LPS-induced microglial activation by suppressing mitogen-activated protein kinase (MAPK) and NF-κB signaling, ultimately reducing proinflammatory responses. Therefore, these antineuroinflammatory effects of 7,3',4'-THIF suggest its potential as a therapeutic agent for neurodegenerative disorders.

Panax notoginseng inhibits LPS-induced pro-inflammatory mediators in microglia (삼칠근(三七根)의 LPS에 의해 활성화된 뇌신경교세포(腦神經膠細胞)로부터의 염증매개물질(炎症媒介物質) 생성억제효과(生成抑制效果))

  • Jung, Hyo-Won;Park, Yong-Ki
    • The Korea Journal of Herbology
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    • v.21 no.4
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    • pp.93-101
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    • 2006
  • Objectives : Increasing evidence has linked chronic inflammation to a number of neurodegenerative disorders including Alzheimer's disease(AD), Parkinson's disease(PD) and Huntington's disease(HD) in the inflammatory process. Uncontrolled activation of microglia may directly toxic to neurons by releasing various substances such as inflammatory cytokines ($TNF-{\alpha}$, $IL-1{\beta}$ and IL-6), NO, PEG2 and superoxide. In this study, the immunomodulatory effects of the herbal extract Panax notoginseng on cultured BV2 microglial cells and primary microglia were investigated to address potential therapeutic or toxic effects. Notoginseng radix extracts extracted from the root of the plant using Methanol. Methods : Cells were stimulated with LPS and treated with notoginseng at different concentrations. Results : Notoginseng significantly decreased LPS-induced production of $TNF-{\alpha}$ and IL-6 by the cultured microglial cells in a dose-dependent manner. The activation of iNOS mRNA and secretion of nitric oxide(NO) in microglial cells were inhibited in microglial cells in a dose-dependent manner by notoginseng. Conclusion : These results indicate that notoginseng inhibits LPS-induced activation of microglial cells and demonstrates notoginseng possess anti-inflammatory and immunosuppressive properties in vitro.

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Sesamin attenuates neuronal damage through inhibition of microglial activation following global cerebral ischemia in rats

  • Kong, Minjung;Hong, Sung In
    • The Korea Journal of Herbology
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    • v.28 no.2
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    • pp.1-7
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    • 2013
  • Objectives : Sesamin, a major lignan in sesame seeds, has been reported to have neuroprotective effects against in vitro ischemia and in vivo MCAo-reperfusion cerebral ischemia model, however, there is no reports in an in vivo global cerebral ischemia model. The purpose of the study was to investigate the neuroprotective effect of sesamin in global cerebral ischemia induced by four-vessel occlusion (4-VO) in rats through inhibition of microglial activation in this model. Methods : The neuroprotective effects were investigated using a 10 min of 4-VO ischemia rat model by measuring intact pyramidal neurons in the CA1 region of the hippocampus using Nissle staining. The antiinflammatory or reducing neurotoxicity effect was investigated using immunohistochemisty, RT-PCR and western blot analysis of inflammatory or neurotoxic mediators. Results : Intraperitoneal injection of sesamin at doses of 0.3, 1.0, 3.0, and 10.0 mg/kg at 0 min and 90 min after ischemia conferred 26.6%, 30.1%, 42.5%, and 30.5% neuroprotection, respectively, compared to the vehicle-treated control group. A 3.0 mg/kg dose of sesamin inhibited microglia activation and consequently, cyclooxygenase-2, inducible nitric oxide, and interleukine-$1{\beta}$ expressions at 48 h after reperfusion. Conclusions : Sesamin protects neuronal cell death through inhibition of microglial activation or the production of neurotoxic metabolites and proinflammatory mediators by microglia such as COX-2, iNOS and IL-$1{\beta}$ in global cerebral ischemia.

Acupuncture inhibits microglial activation in the rat model of Parkinson's disease (파킨슨병 모델 흰쥐에서 침치료에 의한 microglia 활성화 억제에 관한 연구)

  • Hwang, Jeong-Yeon;Choi, Il-Hwan;Park, Jae-Hyun;Kang, Jun-Mo;Park, Hi-Joon;Lim, Sa-Bi-Na
    • Korean Journal of Acupuncture
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    • v.24 no.1
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    • pp.131-144
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    • 2007
  • Objectives : Although the cause of neuronal death of Parkinson's disease remains unclear, increasing evidence points to the role of inflammatory processes. And the hallmark of brain inflammation is the activation of microglia. This study was performed to prove the effect of acupuncture on inhibiting microglial activation. Methods : The rat models which were injected with 6-hydroxydopamine were treated with acupuncture once a day on LR3 (太衝) and GB34 (陽陵泉). To prove the effect of inhibiting microglial activation, we examined the tyrosine hydroxylase (TH) immunopositive neurons and CD11b immunohistochemistry in the substantia nigra. Results : There were 18% (third day), 32% (seventh day) loss of TH-positive cell bodies in the control group and 23% (third day), 26% (seventh day) in the acupuncture group, whereas 3% (third day), 10% (seventh day) in vehicle group. The difference of optical density in substantia nigra was evaluated by subtracting log inverse gray value of contralateral side from that of ipsilateral side. With regards to the result of CD11b immunohistochemistry, acupuncture group showed significantly inhibited microglial activation compared with control group (p<0.01) on the seventh day. Conclusions : Acupuncture showed the effect of inhibition of microglial activation in seventh day. However, the effect of protection of TH positive cell bodies was not shown. So we need longer investigation of the effect of acupuncture on Parkinson's disease.

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Ghrelin Protects Spinal Cord Motoneurons Against Chronic Glutamate Excitotoxicity by Inhibiting Microglial Activation

  • Lee, Sung-Youb;Kim, Yu-Mi;Li, Endan;Park, Seung-Joon
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.1
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    • pp.43-48
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    • 2012
  • Glutamate excitotoxicity is emerging as a contributor to degeneration of spinal cord motoneurons in amyotrophic lateral sclerosis (ALS). Recently, we have reported that ghrelin protects motoneurons against chronic glutamate excitotoxicity through the activation of extracellular signal-regulated kinase 1/2 and phosphatidylinositol-3-kinase/Akt/glycogen synthase kinase-$3{\beta}$ pathways. Previous studies suggest that activated microglia actively participate in the pathogenesis of ALS motoneuron degeneration. However, it is still unknown whether ghrelin exerts its protective effect on motoneurons via inhibition of microglial activation. In this study, we investigate organotypic spinal cord cultures (OSCCs) exposed to threohydroxyaspartate (THA), as a model of excitotoxic motoneuron degeneration, to determine if ghrelin prevents microglial activation. Exposure of OSCCs to THA for 3 weeks produced typical motoneuron death, and treatment of ghrelin significantly attenuated THA-induced motoneuron loss, as previously reported. Ghrelin prevented THA-induced microglial activation in the spinal cord and the expression of pro-inflammatory cytokines tumor necrosis factor-${\alpha}$ and interleukin-$1{\beta}$. Our data indicate that ghrelin may act as a survival factor for motoneurons by functioning as a microglia-deactivating factor and suggest that ghrelin may have therapeutic potential for the treatment of ALS and other neurodegenerative disorders where inflammatory responses play a critical role.

NSA9, a human prothrombin kringle-2-derived peptide, acts as an inhibitor of kringle-2-induced activation in EOC2 microglia

  • Kim, Ji-Yeon;Kim, Tae-Hyong;Kim, Soung-Soo
    • BMB Reports
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    • v.42 no.6
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    • pp.380-386
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    • 2009
  • In neurodegenerative diseases, such as Alzheimer' and Parkinson', microglial cell activation is thought to contribute to CNS injury by producing neurotoxic compounds. Prothrombin and kringle-2 increase levels of NO and the mRNA expression of iNOS, IL-1$\beta$, and TNF-$\alpha$ in microglial cells. In contrast, the human prothrombin kringle-2 derived peptide NSA9 inhibits NO release and the production of pro-inflammatory cytokines such as IL-1$\beta$, TNF-$\alpha$, and IL-6 in LPS-activated EOC2 microglia. In this study, we investigated the anti-inflammatory effects of NSA9 in human prothrombin- and kringle-2-stimulated EOC2 microglia. Treatment with 20-100 ${\mu}M$ of NSA9 attenuated both prothrombin- and kringle-2-induced microglial activation. NO production induced by MAPKs and NF-$\kappa$B was similarly reduced by inhibitors of ERK (PD98059), p38 (SB203580), NF-$\kappa$B (N-acetylcysteine), and NSA9. These results suggest that NSA9 acts independently as an inhibitor of microglial activation and that its effects in EOC2 microglia are not influenced by the presence of kringle-2.

Effect of acupuncture on short-term memory and apoptosis after transient cerebral ischemia in gerbils

  • Choi, In-Ho;Lim, Hyung-Ho
    • The Journal of Korean Medicine
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    • v.39 no.4
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    • pp.1-15
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    • 2018
  • Objectives: Cerebral ischemia results from a variety of causes that cerebral blood flow is reduced due to a transient or permanent occlusion of cerebral arteries. Reactive astrocytes and microglial activation plays an important role in the neuronal cell death during ischemic insult. Acupunctural treatment is effective for symptom improvement in cerebrovascular accident, including cerebral ischemia. Methods: In the present study, the effects of acupuncture at the ST40 acupoint on short-term memory and apoptosis in the hippocampal CA1 region following transient global cerebral ischemia were investigated using gerbils. Transient global ischemia was induced by occlusion of both common carotid arteries with aneurysm clips for 5 min. Acupuncture stimulation was conducted once daily for 7 consecutive days, starting one day after surgery. Results: In the present results, ischemia induction deteriorated short term memory, increased apoptosis, and induced reactive astrocyte and microglial activation. Acupuncture at ST40 acupoint ameliorated ischemia-induced short-term memory impairment by suppressing apoptosis in the hippocampus through down-regulation of reactive astrocytes and microglial activation. Conclusion: The present study suggests that acupuncture at the ST40 acupoint can be used for treatment of patients with cerebral stroke.