International School for Advanced Studies (SISSA/ISAS), 34136Trieste, Italy.
Dipartimento di Medicina Sperimentale e Clinica, University of Florence, 50139Florence, Italy.
ACS Nano. 2023 Feb 14;17(3):1965-1978. doi: 10.1021/acsnano.2c06609. Epub 2023 Jan 24.
In neuroinflammation, astrocytes play multifaceted roles that regulate the neuronal environment. Astrocytes sense and respond to pro-inflammatory cytokines (CKs) and, by a repertoire of intracellular Ca signaling, contribute to disease progression. Therapeutic approaches wish to reduce the overactivation in Ca signaling in inflammatory-reactive astrocytes to restore dysregulated cellular changes. Cell-targeting therapeutics might take advantage by the use of nanomaterial-multifunctional platforms such as graphene oxide (GO). GO biomedical applications in the nervous system involve therapeutic delivery and sensing, and GO flakes were shown to enable interfacing of neuronal and glial membrane dynamics. We exploit organotypic spinal cord cultures and optical imaging to explore Ca changes in astrocytes, and we report, when spinal tissue is exposed to CKs, neuroinflammatory-associated modulation of resident glia. We show the efficacy of GO to revert these dynamic changes in astrocytic reactivity to CKs, and we translate this potential in an animal model of immune-mediated neuroinflammatory disease.
在神经炎症中,星形胶质细胞发挥着多方面的作用,调节神经元环境。星形胶质细胞感知和响应促炎细胞因子(CKs),并通过一系列细胞内钙信号转导,促进疾病进展。治疗方法希望减少炎症反应性星形胶质细胞中钙信号的过度激活,以恢复失调的细胞变化。细胞靶向治疗可以利用纳米材料多功能平台(如氧化石墨烯(GO))来实现优势。GO 在神经系统中的生物医学应用包括治疗药物的输送和检测,并且已经证明 GO 薄片能够实现神经元和神经胶质细胞膜动力学的接口。我们利用器官型脊髓培养物和光学成像来研究星形胶质细胞中的钙变化,并报告了当脊髓组织暴露于 CKs 时,与神经炎症相关的驻留神经胶质细胞的调节。我们展示了 GO 逆转 CKs 引起的星形胶质细胞反应性这些动态变化的功效,并在免疫介导的神经炎症性疾病的动物模型中转化了这种潜力。