Biology subjects

Rosa, J. M.

Publications and source records attributed to Rosa, J. M..

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↗

bioRxiv2020

Cortical layer-specific modulation of neuronal activity after sensory deprivation due to spinal cord injury

Cortical areas have the capacity of large-scale reorganization following sensory deprivation. However, it remains unclear whether this phenomenon is a unique process that homogenously affects an entire deprived cortical region or it is suitable to changes depending on neuronal networks across distinct cortical layers. Here, we studied how local circuitries within each layer of the deprived cortex set the basis for neuroplastic changes after immediate sensory deprivation due to thoracic spinal cord injury (SCI) in anaesthetised rats. In vivo electrophysiological recordings from deprived hindlimb somatosensory cortex showed that SCI induces layer-specific changes mediating evoked and spontaneous activity. In supragranular layers 2/3, sensory deprivation increased gamma oscillations and the ability of these neurons to initiate up-states during spontaneous activity, suggesting altered corticocortical network and/or intrinsic properties that may serve to maintain the excitability of the cortical column after deprivation. On the other hand, sensory deprivation enhanced infragranular layers ability to integrate evoked-sensory inputs leading to increased and faster neuronal responses. Delayed evoked-responses onset were also observed in layers 5/6, suggesting alterations in thalamocortical connectivity. Altogether, our data indicate that SCI immediately modifies local circuitries within the deprived cortex allowing supragranular layers to better integrate spontaneous corticocortical information, and thus modifying column excitability, and infragranular layers to better integrate evoked-sensory inputs to preserve subcortical outputs. These layer-specific neuronal changes may guide the long-term alterations in neuronal excitability and plasticity associated to the rearrangements of somatosensory networks and the appearance of central sensory pathologies usually associated with spinal cord injury.

neuroscience↗

bioRxiv2020

Microglia-to-astrocyte communication modulates synaptic and cerebrovascular functions following traumatic brain injury

Background and purposeActivation of astrocytes contributes to synaptic remodeling, tissue repair and neuronal survival following traumatic brain injury (TBI). However, the mechanisms by which these cells interact to infiltrated inflammatory cells to rewire neuronal networks and repair brain functions remain poorly understood. Here, we explored how TLR4-induced astrocyte activation modified synapses and cerebrovascular integrity following TBI. Experimental approachWe used pharmacological and genetic approaches to determine how functional astrocyte alterations induced by activation of TLR4-pathway in inflammatory cells regulate synapses and neurovascular unit after TBI. For that, we used calcium imaging, immunofluorescence, flow cytometry, blood-brain barrier (BBB) integrity assessment and molecular and behavioral tools. Key resultsShortly after a TBI there is a recruitment of excitable and reactive astrocytes mediated by TLR4-pathway activation with detrimental effects on PSD-95/VGlut1 synaptic puncta, BBB integrity and neurological outcome. Pharmacological blockage of the TLR4-pathway with TAK242 partially reverted many of the observed effects. Synapses and BBB recovery after TAK242 administration were not observed in IP3R2-/- mice, indicating that effects of TLR4-inhibition depend on the subsequent astrocyte activation. In addition, TBI increased the astrocytic-protein thrombospondin-1 necessary to induce a synaptic recovery in a sub-acute phase. Conclusions and implicationsOur data demonstrate that TLR4-mediated signaling, most probably though microglia and/or infiltrated monocyte-astrocyte communication, plays a crucial role in the TBI pathophysiology and that its inhibition prevents synaptic loss and BBB damage accelerating tissue recovery/repair, which might represent a therapeutic potential in CNS injuries and disorders. Declaration of transparency and scientific rigourThis Declaration acknowledges that this paper adheres to the principles for transparent reporting and scientific rigour of preclinical research as stated in the BJP guidelines for Design & Analysis, Immunoblotting and Immunochemistry, and Animal Experimentation, and as recommended by funding agencies, publishers and other organisations engaged with supporting research. Bullet point summaryWhat is already known: O_LIAstrocytes and microglia participate in the early cerebral and synaptic response after traumatic brain injury. C_LIO_LITLR4 antagonism exerts neuroprotection in acute brain injuries. C_LI What this study adds: O_LIAcute astrocyte activation contributes to synaptic loss and BBB breakdown in the acute phase of TBI, and synaptic remodeling in the sub-acute phase. C_LIO_LIAstrocyte activation is mediated by microglia/infiltrating-monocytes activation through TLR4 receptors. C_LI Clinical significance: O_LIInhibition of astrocyte activation through TLR4 antagonism could be a promising option for TBI treatment. C_LI

neuroscience↗