Jung, Gil Y. Lee, Jee Y. Rhim, Hyewhon Oh, Tae H. Yune, Tae Y. 2024-01-20T11:04:14Z 2024-01-20T11:04:14Z 2021-09-05 2013-11 0894-1491 https://pubs.kist.re.kr/handle/201004/127492 Inflammation induced by microglial activation plays a pivotal role in progressive degeneration after traumatic spinal cord injury (SCI). Voltage-gated sodium channels (VGSCs) are also implicated in microglial activation following injury. However, direct evidence that VGSCs are involved in microglial activation after injury has not been demonstrated yet. Here, we show that the increase in VGSC inward current elicited microglial activation followed inflammatory responses, leading to cell death after injury in vitro and in vivo. Isoforms of sodium channel, Na(v)1.1, Na(v)1.2, and Na(v)1.6 were expressed in primary microglia, and the inward current of VGSC was increased by LPS treatment, which was blocked by a sodium channel blocker, tetrodotoxin (TTX). TTX inhibited LPS-induced NF-B activation, expression of TNF-, IL-1 and inducible nitric oxide synthase, and NO production. LPS-induced p38MAPK activation followed pro-nerve growth factor (proNGF) production was inhibited by TTX, whereas LPS-induced JNK activation was not. TTX also inhibited caspase-3 activation and cell death of primary cortical neurons in neuron/microglia co-cultures by inhibiting LPS-induced microglia activation. Furthermore, TTX attenuated caspase-3 activation and oligodendrocyte cell death at 5 d after SCI by inhibiting microglia activation and p38MAPK activation followed proNGF production, which is known to mediate oligodendrocyte cell death. Our study thus suggests that the increase in inward current of VGSC appears to be an early event required for microglia activation after injury. GLIA 2013;61:1807-1821 English WILEY NF-KAPPA-B PROTEIN-KINASE RAT MICROGLIA NA+ CHANNEL CELL-DEATH TNF-ALPHA RECEPTOR ATTENUATION RECOVERY RELEASE An Increase in Voltage-Gated Sodium Channel Current Elicits Microglial Activation Followed Inflammatory Responses In Vitro and In Vivo After Spinal Cord Injury Article 10.1002/glia.22559 1 GLIA, v.61, no.11, pp.1807 - 1821 GLIA 61 11 1807 1821 scie scopus 000325109800004 2-s2.0-84884715747 Neurosciences Neurosciences & Neurology Article NF-KAPPA-B PROTEIN-KINASE RAT MICROGLIA NA+ CHANNEL CELL-DEATH TNF-ALPHA RECEPTOR ATTENUATION RECOVERY RELEASE microglia spinal cord injury tetrodotoxin voltage-gated sodium channels