Biology subjects

Serrano, M. C.

Publications and source records attributed to Serrano, M. C..

3 recordsLinked to original sources

bioRxiv2026

Collagen-based scaffolds loaded with iron oxide nanoparticles promote functional sensorimotor recovery in spinal cord injury

Spinal cord injury disrupts sensorimotor circuits, leading to chronic deficits that require coordinated repair of both spinal and supraspinal circuits. Here, we developed and evaluated a hybrid collagen hydrogel containing chitosan-functionalized iron oxide nanoparticles as a therapeutic scaffold to promote multi-level recovery in a C6 hemisection model in rats. In vitro, both the nanoparticles and the resulting hybrid scaffold show preserved neuronal viability, excitability, and network connectivity. In vivo, scaffold-implanted rats demonstrate significant improvements in gross motor function and postural control, as well as recovery of fine motor skills, forelimb dexterity and grip strength. Sensory evaluations show preserved hindlimb tactile responses accompanied by plasticity within the somatosensory cortex, indicating functional recovery of the different tracts related to sensory and motor functions. At the lesion site, the scaffold enhances neurite outgrowth and modulates the inflammatory milieu, providing a permissive environment for neural repair. These findings indicate that these hybrid collagen scaffolds support relevant integrated structural and functional recovery features after SCI and represent a promising platform for further optimization toward the effective release of therapeutics at the injured spinal cord.

physiology↗

bioRxiv2026

The intracellular region of truncated neurotrophin receptor TrkB-T1 promotes stroke-related effects in glial reactivity and neurotoxicity

The development of advanced therapies for stroke, spinal cord injury or neurodegenerative diseases -main causes of death, disability and dementia- requires a profound understanding of the complex interactions established among excitotoxic neuronal death, aberrant neurotrophic-signaling, glial reactivity, and neuroinflammation. However, the master proteins coordinating these mechanisms have not been yet defined. Different evidence suggests that the truncated form of the neurotrophin tyrosine kinase receptor, TrkB-T1, might play such a key role. The levels of this TrkB isoform increase in stroke while those of the full-length pro-survival isoform (TrkB-FL) are reduced. Additionally, ischemic stroke and, specifically, excitotoxicity induce TrkB-T1 regulated intramembrane proteolysis (RIP), a process releasing a receptor ectodomain able to bind the brain-derived neurotrophic factor (BDNF) and leading to decreased BDNF-signaling. We hypothesize that the second RIP product, TrkB-T1 intracellular domain (TrkB-T1-ICD), might similarly contribute to neurotoxicity but also reactive gliosis and neuroinflammation. Herein, we first demonstrate migration of the cytoplasmic TrkB-T1-ICD to the nuclei of neurons undergoing excitotoxicity, suggesting a possible role in the transcriptional control induced by injury. Then, taking advantage of cell-penetrating peptides (CPPs), we produce a TrkB-T1-ICD mock peptide (Bio-LTT1Ct) containing the short TrkB-T1 intracellular region (23 amino acids) and test it in vitro and in vivo. Notably, this peptide migrates to the nucleus of both neurons and astrocytes cultured in vitro and provokes cell death. Additionally, Bio-LTT1Ct induces early transcriptional changes in neurons resembling those triggered by excitotoxicity such as the inhibition of the promoter activity of pro-survival transcription factors CREB and MEF2, and altered mRNA levels of their regulated genes. In vivo, Bio-LTT1Ct is accessible to the brain cortex after intranasal delivery, being efficiently distributed into cortical neurons and astrocytes of both hemispheres. Moreover, peptide administration is sufficient to promote important pathological hallmarks of stroke such as the imbalance of the TrkB isoforms, and the reactivity of astrocyte and microglia, cells that acquire proinflammatory profiles. Altogether, these results establish TrkB-T1 RIP as a central mechanism of ischemic damage and demonstrate that the receptor intracellular region is sufficient to recapitulate stroke-like effects on neurotoxicity, glial reactivity and neuroinflammation.

neuroscience↗

bioRxiv2023

GRAPHENE OXIDE AS A NOVEL IMMUNOTHERAPY TOOL FOR THE MODULATION OF MYELOID-DERIVED SUPPRESSOR CELL ACTIVITY IN THE CONTEXT OF MULTIPLE SCLEROSIS

Multiple Sclerosis (MS) is a chronic, inflammatory disease of the central nervous system. Despite the pharmacological arsenal approved for MS, there are treatment-reluctant patients for whom cell therapy appears as the only therapeutic alternative. Myeloid-derived suppressor cells (MDSCs) are immature cells of the innate immune response able to immunosuppress T lymphocytes and to promote oligodendroglial differentiation in experimental autoimmune encephalomyelitis (EAE), a preclinical model for MS. Culture devices need to be designed so that MDSCs maintain a state of immaturity and immunosuppressive function similar to that exerted in the donor organism. Graphene oxide (GO) has been described as a biocompatible material with the capacity to biologically modulate different cell types, including immune cells. In the present work, we show how MDSCs isolated from immune organs of EAE mice maintain an immature phenotype and highly immunosuppressive activity on T lymphocytes after being cultured on 2D reduced GO films (rGO200) compared to those grown on glass. This activity is depleted when MDSCs are exposed to slightly rougher and more oxidized GO substrates (rGO90). The greater reduction in cell size of cells exposed to rGO90 compared to rGO200 is associated with the activation of apoptosis processes. Taken together, the exposure of MDSCs to GO substrates with different redox state and roughness appears as a good strategy to control MDSC activity in vitro. This versatility of GO nanomaterials and the impact of their physico-chemical properties in immunomodulation open the door to its possible selective therapeutic use for pathologies where MDSCs need to be enhanced or inhibited.

immunology↗