Photocuring CsA and bFGF-embedded hemostatic hydrogel promotes recovery from TBI by mitigating ferroptosis and neuroinflammation

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-06-09 DOI:10.1016/j.isci.2025.112865

Jianing Shen , Yong Li , Ning Bian , Lu Yang , Yangping Pan , Yuyu Niu , Lu Zhao , Lei Zhang , Jingkuan Wei

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引用次数: 0

Abstract

Traumatic brain injury (TBI) causes focal intracranial hemorrhage, neuroinflammation, and gliosis, which contribute to motor dysfunction. Therapies addressing singular aspects of TBI damage have demonstrated limited efficacy in mitigating its comprehensive impact. Here, we investigated the therapeutic efficacy of a combination therapy comprising cyclosporine A (CsA) and basic fibroblast growth factor (bFGF) during the acute phase of TBI, delivered in a hemostatic hyaluronan-based hydrogel (OCHAMA). The OCHAMA hydrogel substantially reduced iron deposition and inhibited key drivers within the ferroptotic pathway in focal mechanical brain injury. CsA and bFGF-embedded OCHAMA (OCHAMA/CF) treatment resulted in a significant reduction in CD8⁺ T lymphocyte infiltration and interferon-γ (IFN-γ) secretion, which correlated with attenuated neuroinflammation. TBI rats treated with OCHAMA/CF exhibited enhanced neuronal preservation and reduced lesion volume, which was associated with significant recovery of motor function. This therapeutic approach reshaped the peritraumatic neuroinflammatory microenvironment and facilitated neuron survival, underscoring its potential for widespread clinical applicability.

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光固化CsA和bfgf包埋止血水凝胶通过减轻铁下垂和神经炎症促进TBI恢复

外伤性脑损伤（TBI）可引起局灶性颅内出血、神经炎症和神经胶质瘤，从而导致运动功能障碍。针对TBI损伤单一方面的治疗已经证明在减轻其综合影响方面的效果有限。在这里，我们研究了环孢素a （CsA）和碱性成纤维细胞生长因子（bFGF）在TBI急性期联合治疗的疗效，并将其以止血透明质酸为基础的水凝胶（OCHAMA）递送。在局灶性机械性脑损伤中，OCHAMA水凝胶显著减少了铁沉积，抑制了铁迁移途径中的关键驱动因素。CsA和bfgf包埋OCHAMA （OCHAMA/CF）治疗导致CD8+ T淋巴细胞浸润和干扰素γ (IFN-γ)分泌显著减少，这与神经炎症减轻相关。经OCHAMA/CF处理的TBI大鼠神经元保存增强，病变体积减小，运动功能明显恢复。这种治疗方法重塑了创伤周围的神经炎症微环境，促进了神经元的存活，强调了其广泛临床应用的潜力。

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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