PMID- 28359334 OWN - NLM STAT- MEDLINE DCOM- 20180102 LR - 20181113 IS - 1742-2094 (Electronic) IS - 1742-2094 (Linking) VI - 14 IP - 1 DP - 2017 Mar 31 TI - Cytokine cascades induced by mechanical trauma injury alter voltage-gated sodium channel activity in intact cortical neurons. PG - 73 LID - 10.1186/s12974-017-0847-0 [doi] LID - 73 AB - BACKGROUND: Traumatic brain injury (TBI) triggers both immediate (primary) and long-term (secondary) tissue damages. Secondary damages can last from hours to days or even a lifetime. Secondary damages implicate several mechanisms, including influence of inflammatory mediators, mainly cytokines, on excitability of ion channels. However, studies should further explore the effects of inflammatory cytokines on voltage-gated sodium channels (VGSCs) and excitability in distal intact neurons. METHODS: Mixed cultures of mouse cortical astrocytes and neurons were subjected to mechanical injury (trauma) to mimic TBI in vitro. Expression of various cytokines in these cultures were measured by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. A trauma-conditioned medium with or without brain-derived neurotrophic factor (BDNF) was added to mouse primary cortical neurons for 6 and 24 h to mimic combined effects of multiple inflammatory cytokines on VGSCs. Spike behaviors of distal intact neurons were examined by whole-cell patch-clamp recordings. RESULTS: Mechanical injury in mixed cortical neuron-astrocyte cultures significantly increased expression levels of multiple cytokines, including interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, chemokine (C-C motif) ligand-5, IL-10, and transforming growth factor-beta1, at 6 and 24 h after injury. Incubation in trauma-conditioned medium increased functional VGSCs in neuronal membranes and Na(+) currents. Enhanced VGSCs were almost completely abolished by BDNF, and reinforcement of Na(+) currents was also reduced in a dose-dependent manner. BDNF (30 ng/mL) also significantly reversed reduced neuronal cell viability, which was induced by medium conditioned at 6 h. At 6 and 24 h, trauma-conditioned medium significantly increased spike frequency but not spike threshold. CONCLUSIONS: In TBI, the combined effect of inflammatory cytokines is directly involved in VGSC, Na(+) current, and excitability dysfunction in distal intact neurons. BDNF may partly exert neuroprotective effects by maintaining balance of VGSC function in distal intact neurons. FAU - Chen, Weiqiang AU - Chen W AD - Department of Neurosurgery, Fuzhou General Hospital, Xiamen University Medical College, 156 North Road, West Second Ring, Fuzhou, 350025, Fujian, China. AD - Department of Neurosurgery, First Affiliated Hospital, Shantou University Medical College, 57 Changping Road, Shantou, 515041, Guangdong, China. FAU - Sheng, Jiangtao AU - Sheng J AD - Department of Microbiology and Immunology, Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, 22 Xinling Road, Shantou, 515041, Guangdong, China. FAU - Guo, Jingfang AU - Guo J AD - Department of Neurosurgery, First Affiliated Hospital, Shantou University Medical College, 57 Changping Road, Shantou, 515041, Guangdong, China. FAU - Peng, Guoyi AU - Peng G AD - Department of Neurosurgery, First Affiliated Hospital, Shantou University Medical College, 57 Changping Road, Shantou, 515041, Guangdong, China. FAU - Hong, Jinfang AU - Hong J AD - Department of Neurosurgery, Fuzhou General Hospital, Xiamen University Medical College, 156 North Road, West Second Ring, Fuzhou, 350025, Fujian, China. FAU - Li, Bingbing AU - Li B AD - Department of Neurosurgery, Fuzhou General Hospital, Xiamen University Medical College, 156 North Road, West Second Ring, Fuzhou, 350025, Fujian, China. FAU - Chen, Xiaoxuan AU - Chen X AD - Department of Microbiology and Immunology, Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, 22 Xinling Road, Shantou, 515041, Guangdong, China. FAU - Li, Kangsheng AU - Li K AD - Department of Microbiology and Immunology, Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, 22 Xinling Road, Shantou, 515041, Guangdong, China. ksli2013@yeah.net. FAU - Wang, Shousen AU - Wang S AD - Department of Neurosurgery, Fuzhou General Hospital, Xiamen University Medical College, 156 North Road, West Second Ring, Fuzhou, 350025, Fujian, China. wshsen@xmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170331 PL - England TA - J Neuroinflammation JT - Journal of neuroinflammation JID - 101222974 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cytokines) RN - 0 (Voltage-Gated Sodium Channels) SB - IM MH - Animals MH - Brain Injuries, Traumatic/*metabolism MH - Brain-Derived Neurotrophic Factor/metabolism MH - Cells, Cultured MH - Cerebral Cortex/metabolism MH - Cytokines/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Neurons/*metabolism MH - Voltage-Gated Sodium Channels/*metabolism PMC - PMC5374609 OTO - NOTNLM OT - Brain-derived neurotrophic factor OT - Cytokine cascades OT - Inflammatory microenvironment OT - Mechanical brain injury OT - Nerve excitability OT - Voltage-gated sodium channel EDAT- 2017/04/01 06:00 MHDA- 2018/01/03 06:00 PMCR- 2017/03/31 CRDT- 2017/04/01 06:00 PHST- 2016/09/14 00:00 [received] PHST- 2017/03/21 00:00 [accepted] PHST- 2017/04/01 06:00 [entrez] PHST- 2017/04/01 06:00 [pubmed] PHST- 2018/01/03 06:00 [medline] PHST- 2017/03/31 00:00 [pmc-release] AID - 10.1186/s12974-017-0847-0 [pii] AID - 847 [pii] AID - 10.1186/s12974-017-0847-0 [doi] PST - epublish SO - J Neuroinflammation. 2017 Mar 31;14(1):73. doi: 10.1186/s12974-017-0847-0.