Graphene Oxide Nanosheets Reduce Astrocyte Reactivity to Inflammation and Ameliorate Experimental Autoimmune Encephalomyelitis.
Giuseppe Di MauroRoberta AmorielloNeus LozanoAlberto CarnascialiDaniele GuastiMaurizio BecucciGiada CellotKostas KostarelosClara BalleriniLaura BalleriniPublished in: ACS nano (2023)
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 2+ signaling, contribute to disease progression. Therapeutic approaches wish to reduce the overactivation in Ca 2+ 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 2+ 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.
Keyphrases
- spinal cord
- high resolution
- oxidative stress
- neuropathic pain
- cerebral ischemia
- protein kinase
- cancer therapy
- drug delivery
- small molecule
- traumatic brain injury
- stem cells
- cell therapy
- quality improvement
- mesenchymal stem cells
- mass spectrometry
- human health
- bone marrow
- highly efficient
- high speed
- high throughput sequencing