Chemobrain is a well-established clinical syndrome that impairs patient's daily function, in particular attentiveness, coordination and multi-tasking. Thus, it interferes with patient's quality of life. The putative pharmacological intervention against chemobrain relies on understanding the molecular mechanisms underlying it. This study aimed to examine the potential neuroprotective effects of two immunomodulators: Interferon-β-1a (IFN-β-1a), as well as Tumor necrosis function-alpha (TNF-α) inhibitor; Infliximab in doxorubicin (DOX)-induced chemobrain in rats. Besides, the current study targets investigating the possible molecular mechanisms in terms of neuromodulation and interference with different death routes controlling neural homeostasis. Herein, the two immunomodulators IFN-β-1a at a dose of 300,000 units; s.c.three times per week, or Infliximab at a dose of 5 mg/kg/week; i.p. once per week were examined against DOX (2 mg/kg/w, i.p.) once per week for 4 consecutive weeks in rats.The consequent behavioral tests and markers for cognitive impairment, oxidative stress, neuroinflammation, apoptosis and neurobiological abnormalities were further evaluated. Briefly, IFN-β-1a or Infliximab significantly protected against DOX-induced chemobrain. IFN-β-1a or Infliximab ameliorated DOX-induced hippocampal histopathological neurodegenerative changes, halted DOX-induced cognitive impairment, abrogated DOX-induced mitochondrial oxidative, inflammatory and apoptotic stress, mitigated DOX-induced autophagic dysfunction and finally upregulated the mitophagic machineries. In conclusion, these findings suggest that either IFN-β-1a or Infliximab offers neuroprotection against DOX-induced chemobrain which could be explained by their antioxidant, anti-inflammatory, pro-autophagic, pro-mitophagic and antiapoptotic effects. Future clinical studies are recommended to personalize either use of IFN-β-1a or infliximab to ameliorate DOX-induced chemobrain.

化疗脑是一种公认​​的临床综合征，会损害患者的日常功能，尤其是注意力、协调性和多任务处理能力。因此，它会影响患者的生活质量。针对化学脑的推定药理学干预依赖于了解其背后的分子机制。本研究旨在检测两种免疫调节剂的潜在神经保护作用：干扰素-β-1a (IFN-β-1a)，以及肿瘤坏死功能-α (TNF-α) 抑制剂；英夫利昔单抗在多柔比星 (DOX) 诱导的大鼠化学脑中的作用。此外，目前的研究旨在调查神经调节和干扰控制神经稳态的不同死亡途径的可能分子机制。在此，两种免疫调节剂IFN-β-1a的剂量为300,000单位；一周三次，或英夫利昔单抗，剂量为 5 mg/kg/周；每周一次腹腔注射针对 DOX（2 mg/kg/w，腹腔注射）每周一次连续 4 周在大鼠中进行检查。进一步评估随后的行为测试和认知障碍、氧化应激、神经炎症、细胞凋亡和神经生物学异常的标志物. 简而言之，IFN-β-1a 或英夫利昔单抗可显着防止 DOX 诱导的化学脑。IFN-β-1a 或英夫利昔单抗改善了 DOX 诱导的海马组织病理学神经退行性变化，阻止了 DOX 诱导的认知障碍，消除了 DOX 诱导的线粒体氧化、炎症和凋亡应激，减轻了 DOX 诱导的自噬功能障碍，并最终上调了线粒体自噬机制。综上所述，这些发现表明，IFN-β-1a 或英夫利昔单抗可提供针对 DOX 诱导的化学脑的神经保护作用，这可以通过它们的抗氧化、抗炎、促自噬、促线粒体自噬和抗细胞凋亡作用来解释。建议未来的临床研究个性化使用 IFN-β-1a 或英夫利昔单抗来改善 DOX 诱导的化学脑。