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A Comparative Investigation of Axon-Blood Vessel Growth Interaction in the Regenerating Sciatic and Optic Nerves in Adult Mice

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Abstract

The vascular and the nervous systems share similarities in addition to their complex role in providing oxygen and nutrients to all cells. Both are highly branched networks that frequently grow close to one another during development. Vascular patterning and neural wiring share families of guidance cues and receptors. Most recently, this relationship has been investigated in terms of peripheral nervous system (PNS) regeneration, where nerves and blood vessels often run in parallel so endothelial cells guide the formation of the Büngner bands which support axonal regeneration. Here, we characterized the vascular response in regenerative models of the central and peripheral nervous system. After sciatic nerve crush, followed by axon regeneration, there was a significant increase in the blood vessel density 7 days after injury. In addition, the optic nerve crush model was used to evaluate intrinsic regenerative potential activated with a combined treatment that stimulated retinal ganglion cells (RGCs) regrowth. We observed that a 2-fold change in the total number of blood vessels occurred 7 days after optic nerve crush compared to the uncrushed nerve. The difference increased up to a 2.7-fold change 2 weeks after the crush. Interestingly, we did not observe differences in the total number of blood vessels 2 weeks after crush, compared to animals that had received combined treatment for regeneration and controls. Therefore, the vascular characterization showed that the increase in vascular density was not related to the efficiency of both peripheral and central axonal regeneration.

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Data Availability

The data supporting the findings of this study are available in Github at https://github.com/victorresend/Barbara-s-manuscript-files.git, reference number: #001. These data were derived from the following resources available in the public domain: (https://drive.google.com/drive/folders/164kwm_07smXNLJEUnofZVPwhTX6lO7j?usp=share_link and https://drive.google.com/drive/folders/1-Gi36nlNth%2D%2DntbHnxHPU52BN332-zK4?usp=share_link).

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Acknowledgements

The authors are grateful to Luciano Cavalcante for the laboratory technical support. We also are grateful for grant support from Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro, and the National Institute for Translational Neuroscience.

Funding

This work was supported by grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq VTRR 2014; CNPq VTRR 2018, CNPq RAMR PQ2), the Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (Faperj VTRR 2013; Faperj VTRR 2015; Faperj RAMR 2019), and the INCT-INNT (RAMR National Institute for Translational Neuroscience).

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Authors and Affiliations

  1. Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil

    Barbara Rangel da Silva, Ricardo A. de Melo Reis & Victor Túlio Ribeiro-Resende

  2. Núcleo Multidisciplinar de Pesquisa em Biologia (Numpex-Bio), Campus de Duque de Caxias Geraldo Cidade, Universidade Federal do Rio de Janeiro, Duque de Caxias, Brazil

    Victor Túlio Ribeiro-Resende

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BRS: performed all the animal handling experiments, tissue processing, immunolabeling, and quantitative analysis; analyzed the data imaging by optical microscopy; and wrote and discussed the manuscript. RAMR: analyzed the data and wrote and discussed the manuscript. VTRR: general coordinator, analyzed the data, and discussed and wrote the manuscript.

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Correspondence to Victor Túlio Ribeiro-Resende.

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All Animal handling and surgical procedures were carried out in accordance with the approved guidelines for the Use of Animals in Research from the Federal University of Rio de Janeiro (CEUA IBCCF protocol#175-18) and from National Institutes of Health Guidelines for the Care and Use of Laboratory Animals.

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da Silva, B.R., de Melo Reis, R.A. & Ribeiro-Resende, V.T. A Comparative Investigation of Axon-Blood Vessel Growth Interaction in the Regenerating Sciatic and Optic Nerves in Adult Mice. Mol Neurobiol 61, 2215–2227 (2024). https://doi.org/10.1007/s12035-023-03705-0

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