Urolithin A(UA)is a natural metabolite produced from polyphenolics in foods such as pomegranates,berries,and nuts.UA is neuroprotective against Parkinson’s disease,Alzheimer’s disease,and cerebral hemorrhage.However...Urolithin A(UA)is a natural metabolite produced from polyphenolics in foods such as pomegranates,berries,and nuts.UA is neuroprotective against Parkinson’s disease,Alzheimer’s disease,and cerebral hemorrhage.However,its effect against traumatic brain injury remains unknown.In this study,we established adult C57BL/6J mouse models of traumatic brain injury by controlled cortical impact and then intraperitoneally administered UA.We found that UA greatly reduced brain edema;increased the expression of tight junction proteins in injured cortex;increased the immunopositivity of two neuronal autophagy markers,microtubule-associated protein 1A/B light chain 3A/B(LC3)and p62;downregulated protein kinase B(Akt)and mammalian target of rapamycin(mTOR),two regulators of the phosphatidylinositol 3-kinase(PI3K)/Akt/mTOR signaling pathway;decreased the phosphorylation levels of inhibitor of NFκB(IκB)kinase alpha(IKKα)and nuclear factor kappa B(NFκB),two regulators of the neuroinflammation-related Akt/IKK/NFκB signaling pathway;reduced blood-brain barrier permeability and neuronal apoptosis in injured cortex;and improved mouse neurological function.These findings suggest that UA may be a candidate drug for the treatment of traumatic brain injury,and its neuroprotective effects may be mediated by inhibition of the PI3K/Akt/mTOR and Akt/IKK/NFκB signaling pathways,thus reducing neuroinflammation and enhancing autophagy.展开更多
This paper reveals the formation of annular lamellar body (ALB) in the ganglion of leech by means of in situ fixation and the lanthanum nitrate tracer technique. This formation involves both wrapping and internalizati...This paper reveals the formation of annular lamellar body (ALB) in the ganglion of leech by means of in situ fixation and the lanthanum nitrate tracer technique. This formation involves both wrapping and internalization of the gap junctions between glial processes themselves, as well as between neuron and glial process. The results indicate that there is probably an active process of internalization of membrane structures involving gap junctions between neuron and glial cell in the central nervous system in leech. The functions of ALB are discussed.展开更多
Brain connectivity is commonly studied in terms of causal interaction or statistical dependency between brain regions. In this analysis paper, we draw attention to the constraining effect the dynamics of fiber tract c...Brain connectivity is commonly studied in terms of causal interaction or statistical dependency between brain regions. In this analysis paper, we draw attention to the constraining effect the dynamics of fiber tract connections may impose on neuronal signal traffic. We propose a model developed by Copelli and Kinouchi (l.c.) for a different purpose to safeguard signal transmission for brain connectivity by ensuring dynamic adaptation of signal reception to a wide frequency range of traffic flow over connecting fiber tracts. Gap junction connectivity would confer to neuronal groups the capacity of acting as collectives for dynamical adaptability to impinging neural traffic thereby forestalling traffic congestion and overload. It is suggested that applying this model to signal reception in brain connectivity would deliver the required functionality as a collective achievement of the interrelations between neurons and gap junctions, the latter regulated by glia.展开更多
Gap junction blocking agents can inhibit spontaneous discharge frequency in cells. We established a rat model of posttraumatic epilepsy induced using ferric ions. Rats were intraperitoneally injected with carbenoxolon...Gap junction blocking agents can inhibit spontaneous discharge frequency in cells. We established a rat model of posttraumatic epilepsy induced using ferric ions. Rats were intraperitoneally injected with carbenoxolone, 20 mg/kg, prior to and 30 minutes after model establishment, once a day for 14 consecutive days. Immunohistochemistry showed glial cell proliferation around a cortical focus and significantly increased connexin expression in posttraumatic epilepsy. However, carbenoxolone pretreatment or treatment significantly reduced connexin expression in the cortex, inhibited glial fibdllary acidic protein expression and ameliorated seizure degree in rats. These findings indicate that large amounts of glial cell proliferation and abnormal gap junction generation play a role in posttraumatic epilepsy, and that carbenoxolone may prevent and treat this disease.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81974189(to HLT),81801236(to QYG and LC),82001310(to DXY).
文摘Urolithin A(UA)is a natural metabolite produced from polyphenolics in foods such as pomegranates,berries,and nuts.UA is neuroprotective against Parkinson’s disease,Alzheimer’s disease,and cerebral hemorrhage.However,its effect against traumatic brain injury remains unknown.In this study,we established adult C57BL/6J mouse models of traumatic brain injury by controlled cortical impact and then intraperitoneally administered UA.We found that UA greatly reduced brain edema;increased the expression of tight junction proteins in injured cortex;increased the immunopositivity of two neuronal autophagy markers,microtubule-associated protein 1A/B light chain 3A/B(LC3)and p62;downregulated protein kinase B(Akt)and mammalian target of rapamycin(mTOR),two regulators of the phosphatidylinositol 3-kinase(PI3K)/Akt/mTOR signaling pathway;decreased the phosphorylation levels of inhibitor of NFκB(IκB)kinase alpha(IKKα)and nuclear factor kappa B(NFκB),two regulators of the neuroinflammation-related Akt/IKK/NFκB signaling pathway;reduced blood-brain barrier permeability and neuronal apoptosis in injured cortex;and improved mouse neurological function.These findings suggest that UA may be a candidate drug for the treatment of traumatic brain injury,and its neuroprotective effects may be mediated by inhibition of the PI3K/Akt/mTOR and Akt/IKK/NFκB signaling pathways,thus reducing neuroinflammation and enhancing autophagy.
基金Project supported by the National Natural Science Foundation of China, Research Grant of National Education Commission and Grant of Beijing Zhongguancun Associated Center of Analysis and Measurement
文摘This paper reveals the formation of annular lamellar body (ALB) in the ganglion of leech by means of in situ fixation and the lanthanum nitrate tracer technique. This formation involves both wrapping and internalization of the gap junctions between glial processes themselves, as well as between neuron and glial process. The results indicate that there is probably an active process of internalization of membrane structures involving gap junctions between neuron and glial cell in the central nervous system in leech. The functions of ALB are discussed.
文摘Brain connectivity is commonly studied in terms of causal interaction or statistical dependency between brain regions. In this analysis paper, we draw attention to the constraining effect the dynamics of fiber tract connections may impose on neuronal signal traffic. We propose a model developed by Copelli and Kinouchi (l.c.) for a different purpose to safeguard signal transmission for brain connectivity by ensuring dynamic adaptation of signal reception to a wide frequency range of traffic flow over connecting fiber tracts. Gap junction connectivity would confer to neuronal groups the capacity of acting as collectives for dynamical adaptability to impinging neural traffic thereby forestalling traffic congestion and overload. It is suggested that applying this model to signal reception in brain connectivity would deliver the required functionality as a collective achievement of the interrelations between neurons and gap junctions, the latter regulated by glia.
基金supported by the Social Development Program of Nantong, No. S2009035
文摘Gap junction blocking agents can inhibit spontaneous discharge frequency in cells. We established a rat model of posttraumatic epilepsy induced using ferric ions. Rats were intraperitoneally injected with carbenoxolone, 20 mg/kg, prior to and 30 minutes after model establishment, once a day for 14 consecutive days. Immunohistochemistry showed glial cell proliferation around a cortical focus and significantly increased connexin expression in posttraumatic epilepsy. However, carbenoxolone pretreatment or treatment significantly reduced connexin expression in the cortex, inhibited glial fibdllary acidic protein expression and ameliorated seizure degree in rats. These findings indicate that large amounts of glial cell proliferation and abnormal gap junction generation play a role in posttraumatic epilepsy, and that carbenoxolone may prevent and treat this disease.
