PMID- 36028204 OWN - NLM STAT- MEDLINE DCOM- 20221108 LR - 20221116 IS - 1873-6300 (Electronic) IS - 0891-0618 (Linking) VI - 125 DP - 2022 Nov TI - The role of Tenascin C in intracerebral hemorrhage-induced secondary brain injury in rats via induction of neuronal cell death and neuroinflammation. PG - 102147 LID - S0891-0618(22)00077-1 [pii] LID - 10.1016/j.jchemneu.2022.102147 [doi] AB - BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) is a major cause of stroke that causes high rates of disability and mortality in adults. Tenascin C (TNC) protein, one of the matricellular proteins associated with platelet-derived growth factor receptor (PDGFR) activation, has been reported to induce neuronal apoptosis. However, the role and underlying mechanisms of TNC in ICH-induced secondary brain injury (SBI) have not yet been fully explained. The main purpose of this study was to explore the role of TNC and its potential mechanisms in ICH. METHODS: An ICH model was established by injecting autologous blood into the right basal ganglia in male Sprague Dawley (SD) rats, and imatinib, an inhibitor of PDGFR, was used to inhibit the release of TNC. RESULTS: We found that TNC protein was significantly increased in the brain tissues after ICH and expressed in both neurons and microglia. We also found that the TNC level was elevated in the cerebrospinal fluid (CSF) after ICH. Additionally, we observed that the infiltration of activated microglia and the release of TNFalpha and IL-1beta induced by ICH were decreased after inhibition of the protein levels of TNC and cleaved-TNC by a chemical inhibitor (imatinib). Furthermore, imatinib improved neuronal cell death and neurobehavioral abnormalities induced by ICH. CONCLUSION: In summary, our study revealed that TNC protein plays an important role in ICH-induced SBI, and inhibition of TNC could alleviate ICH-induced neuroinflammation, neuronal cell death, and neurobehaviour. Therefore, TNC may be a potential therapeutic target for ICH-induced SBI. CI - Copyright (c) 2022 Elsevier B.V. All rights reserved. FAU - Ding, Jiasheng AU - Ding J AD - Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu Province, China; Institute of Stroke Research, Soochow University, China. FAU - Lian, Jinrong AU - Lian J AD - Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu Province, China; Institute of Stroke Research, Soochow University, China. FAU - Wang, Jiahe AU - Wang J AD - Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu Province, China; Institute of Stroke Research, Soochow University, China. FAU - Yang, Siyuan AU - Yang S AD - Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu Province, China; Institute of Stroke Research, Soochow University, China. FAU - Li, Haiying AU - Li H AD - Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu Province, China; Institute of Stroke Research, Soochow University, China. FAU - Shen, Haitao AU - Shen H AD - Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu Province, China; Institute of Stroke Research, Soochow University, China. FAU - Sun, Qing AU - Sun Q AD - Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu Province, China; Institute of Stroke Research, Soochow University, China. Electronic address: qsun@suda.edu.cn. FAU - Li, Xiang AU - Li X AD - Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu Province, China; Institute of Stroke Research, Soochow University, China. Electronic address: xiangli2017@suda.edu.cn. FAU - Chen, Gang AU - Chen G AD - Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu Province, China; Institute of Stroke Research, Soochow University, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220824 PL - Netherlands TA - J Chem Neuroanat JT - Journal of chemical neuroanatomy JID - 8902615 RN - 0 (Tenascin) RN - 8A1O1M485B (Imatinib Mesylate) SB - IM MH - Animals MH - Rats MH - Male MH - *Tenascin/metabolism MH - Rats, Sprague-Dawley MH - Imatinib Mesylate/pharmacology MH - Neuroinflammatory Diseases MH - Cerebral Hemorrhage/complications/metabolism MH - Cell Death/physiology MH - *Brain Injuries/complications/drug therapy/metabolism MH - Disease Models, Animal OTO - NOTNLM OT - Intracerebral hemorrhage OT - Neuroinflammation OT - Neuronal cell death OT - Secondary brain injury OT - Tenascin C COIS- Declaration of Competing Interest The authors declare that they have no competing interests. EDAT- 2022/08/27 06:00 MHDA- 2022/11/09 06:00 CRDT- 2022/08/26 19:28 PHST- 2022/03/15 00:00 [received] PHST- 2022/08/18 00:00 [revised] PHST- 2022/08/22 00:00 [accepted] PHST- 2022/08/27 06:00 [pubmed] PHST- 2022/11/09 06:00 [medline] PHST- 2022/08/26 19:28 [entrez] AID - S0891-0618(22)00077-1 [pii] AID - 10.1016/j.jchemneu.2022.102147 [doi] PST - ppublish SO - J Chem Neuroanat. 2022 Nov;125:102147. doi: 10.1016/j.jchemneu.2022.102147. Epub 2022 Aug 24.