PMID- 29790836 OWN - NLM STAT- MEDLINE DCOM- 20190801 LR - 20211204 IS - 1522-1598 (Electronic) IS - 0022-3077 (Linking) VI - 120 IP - 3 DP - 2018 Sep 1 TI - Minocycline promotes posthemorrhagic neurogenesis via M2 microglia polarization via upregulation of the TrkB/BDNF pathway in rats. PG - 1307-1317 LID - 10.1152/jn.00234.2018 [doi] AB - Intracerebral hemorrhage (ICH) is a devastating disease worldwide with increasing mortality. The present study investigated whether minocycline was neuroprotective and induced M2 microglial polarization via upregulation of the TrkB/BDNF pathway after ICH. ICH was induced via injection of autologous blood into 150 Sprague-Dawley rats. A selective TrkB antagonist [N2-2-2-oxoazepan-3-yl amino] carbonyl phenyl benzo (b) thiophene-2-carboxamide (ANA 12)] and agonist [ N-[2-(5-hydroxy-1H-indol-3-yl) ethyl]-2-oxopiperidine-3-carboxamide (HIOC)] were used to investigate the mechanism of minocycline-induced neuroprotection. Minocycline improved ICH-induced neurological deficits and reduced M1 microglia marker protein (CD68, CD16) expression as well as M2 microglial polarization (CD206 and arginase 1 protein). Minocycline administration enhanced microglia-neuron cross talk and promoted the proliferation of neuronal progenitor cells, such as DCX- and Tuj-1-positive cells, 24 h after ICH. Minocycline also increased M2 microglia-derived brain-derived neurotrophic factors (BDNF) and the upstream TrkB pathway. ANA 12 reversed the neuroprotective effects of minocycline. HIOC exhibited the same effects as minocycline and accelerated neurogenesis after ICH. This study demonstrated for the first time that minocycline promoted M2 microglia polarization via upregulation of the TrkB/BDNF pathway and promoted neurogenesis after ICH. This study contributes to our understanding of the therapeutic potential of minocycline in ICH. NEW & NOTEWORTHY The present study gives several novel points: 1) Minocycline promotes neurogenesis after intracerebral hemorrhage in rats. 2) Minocycline induces activated M1 microglia into M2 neurotrophic phenotype. 3) M2 microglia secreting BDNF remodel the damaged neurocircuit. FAU - Miao, Hongsheng AU - Miao H AD - Department of Neurosurgery, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine. FAU - Li, Runming AU - Li R AD - Department of Neurosurgery, No. 205 Hospital of People's Liberation Army of China, Jingzhou, China. FAU - Han, Cong AU - Han C AD - Department of Neurosurgery, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine. FAU - Lu, Xiuzhen AU - Lu X AD - Department of Neurosurgery, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine. FAU - Zhang, Hang AU - Zhang H AD - Department of Neurosurgery, No. 205 Hospital of People's Liberation Army of China, Jingzhou, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180523 PL - United States TA - J Neurophysiol JT - Journal of neurophysiology JID - 0375404 RN - 0 (Bdnf protein, rat) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Dcx protein, rat) RN - 0 (Doublecortin Protein) RN - 0 (Neuroprotective Agents) RN - EC 2.7.10.1 (Ntrk2 protein, rat) RN - EC 2.7.10.1 (Receptor, trkB) RN - FYY3R43WGO (Minocycline) MH - Animals MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Cerebral Cortex/drug effects/physiopathology MH - Cerebral Hemorrhage/physiopathology/*prevention & control MH - Doublecortin Protein MH - Maze Learning/drug effects MH - Microglia/*drug effects/metabolism MH - Minocycline/*administration & dosage MH - Neurogenesis/*drug effects MH - Neuroprotective Agents/*administration & dosage MH - Rats, Sprague-Dawley MH - Receptor, trkB/*metabolism MH - Signal Transduction/drug effects MH - Up-Regulation OTO - NOTNLM OT - ICH OT - TrkB/BDNF pathway OT - microglial polarization OT - minocycline OT - neurogenesis EDAT- 2018/05/24 06:00 MHDA- 2019/08/02 06:00 CRDT- 2018/05/24 06:00 PHST- 2018/05/24 06:00 [pubmed] PHST- 2019/08/02 06:00 [medline] PHST- 2018/05/24 06:00 [entrez] AID - 10.1152/jn.00234.2018 [doi] PST - ppublish SO - J Neurophysiol. 2018 Sep 1;120(3):1307-1317. doi: 10.1152/jn.00234.2018. Epub 2018 May 23.