The role of Tenascin C in intracerebral hemorrhage-induced secondary brain injury in rats via induction of neuronal cell death and neuroinflammation
The role of Tenascin C in intracerebral hemorrhage-induced secondary brain injury in rats via induction of neuronal cell death and neuroinflammation
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DOI：
10.1016/j.jchemneu.2022.102147
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发表时间：
2022-08-26
影响因子：
2.8
通讯作者：
Chen, Gang
中科院分区：
文献类型：
--
作者：
Ding, Jiasheng;Lian, Jinrong;Chen, Gang
背景：自发性脑出血（ICH）是导致成人高致残率和死亡率的脑卒中的主要原因。Tenascin C （TNC）蛋白是一种与血小板衍生生长因子受体（PDGFR）激活相关的基质细胞蛋白，已被报道可诱导神经元凋亡。然而，TNC在ich诱导的继发性脑损伤（SBI）中的作用和潜在机制尚未得到充分解释。本研究的主要目的是探讨TNC在ICH中的作用及其潜在机制。方法：采用自体血注入雄性SD大鼠右侧基底节区建立脑出血模型，采用PDGFR抑制剂伊马替尼抑制TNC释放。结果：我们发现脑出血后脑组织中TNC蛋白明显升高，且在神经元和小胶质细胞中均有表达。我们还发现脑脊液（CSF）中TNC水平升高。此外，我们观察到，化学抑制剂（伊马替尼）抑制TNC和切割-TNC蛋白水平后，激活的小胶质细胞的浸润和ICH诱导的TNF α和IL-1 β的释放减少。此外，伊马替尼改善脑出血引起的神经元细胞死亡和神经行为异常。结论：综上所述，我们的研究揭示了TNC蛋白在ich诱导的SBI中发挥重要作用，抑制TNC可以减轻ich诱导的神经炎症、神经元细胞死亡和神经行为。因此，TNC可能是ich诱导SBI的潜在治疗靶点。
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 TNF alpha and IL-1 beta 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.