Biology subjects

Saude, L.

Publications and source records attributed to Saude, L..

3 recordsLinked to original sources

bioRxiv2024

Neutrophil immune profile controls spinal cord regeneration in zebrafish

Spinal cord injury triggers a strong innate inflammatory response in both non-regenerative mammals and regenerative zebrafish. Neutrophils are the first immune population to be recruited to the injury site. Yet, their role in the repair process, particularly in a regenerative context, remains largely unknown. Here, we show that, following rapid recruitment to the injured spinal cord, neutrophils mostly reverse migrate throughout the zebrafish body. In addition, promoting neutrophil inflammation resolution by inhibiting Cxcr4 boosts cellular and functional regeneration. Neutrophil-specific RNA-seq analysis reveals an enhanced activation state that correlates with a transient increase in tnf- expression in macrophage/microglia populations. Conversely, blocking neutrophil recruitment through Cxcr1/2 inhibition diminishes the presence of macrophage/microglia at the injury site and impairs spinal cord regeneration. Altogether, these findings provide new insights into the role of neutrophils in spinal cord regeneration, emphasizing the significant impact of their immune profile on the outcome of the repair process. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=185 HEIGHT=200 SRC="FIGDIR/small/576035v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@6153f1org.highwire.dtl.DTLVardef@1ce09faorg.highwire.dtl.DTLVardef@1f11187org.highwire.dtl.DTLVardef@1b5c152_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2022

New functional vessels form after spinal cord injury in zebrafish

The vascular system is inefficiently repaired after spinal cord injury in mammals, resulting in secondary tissue damage and immune deregulation that contribute to the limited functional recovery. Unlike mammals, zebrafish can repair the spinal cord and restore motility, but the vascular response to injury has not been investigated. Here we describe the zebrafish spinal cord vasculature, from the body size-dependent vessel ingression during development to the stereotypic vessel organization and barrier specialisation in adulthood. After injury, vessels rapidly regrow into the lesion, preceding the glial bridge and regenerating axons. The initial vascularisation of the injured tissue is done by dysmorphic and leaky vessels. Dysfunctional vessels are later removed, as pericytes are recruited and the blood-spinal cord barrier is re-established. Vascular repair involves an early burst of angiogenesis, likely in response to pro-angiogenic factors detected in the injured spinal cord, including the Vegf pathway. However, the inhibition of the Vegfr2 using genetic and pharmacological methods was not able to efficiently block the formation of new blood vessels, suggesting that other signalling pathways are also involved in this process. This study demonstrates that zebrafish can successfully re-vascularise the spinal tissue, reinforcing the value of this organism as a regenerative model for spinal cord injury.

developmental biology↗

bioRxiv2020

Depletion of senescent cells improves functional recovery after spinal cord injury

Persistent senescent cells (SCs) are known to underlie ageing-related chronic disorders, but it is now recognized that SCs may be at the center of tissue remodeling events, namely during development or organ repair. Here we show that two distinct senescence profiles are induced in the context of a spinal cord injury between the regenerating zebrafish and the non-regenerating mouse. While induced-SCs in the zebrafish are progressively cleared out, they accumulate over time in mice. Depletion of SCs in spinal cord injured mice, with different senolytic drugs, improved locomotor, sensory and bladder functions. This functional recovery is associated with improved myelin sparing, reduced fibrotic scar, attenuated inflammation and increased axonal growth. Targeting SCs is a promising therapeutic strategy not only for spinal cord injuries but potentially for other organs that lack regenerative competence.

neuroscience↗