Unraveling the role of neutrophils during spinal cord regeneration in zebrafish

• Autor(a) principal: Lameira, Maria Leonor Rebola
• Data de Publicação: 2022
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/132079
• topic: Spinal cord; Spinal Cord Injury; Inflammation; Neutrophils; Regeneration; Zebrafish; Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias

The spinal cord is a key component of the central nervous system, and it enables the communication between the brain and the body. Injuries in the spinal cord result not only in loss of sensitive and motor function, but also in long-term complications that increase the morbidity of the patients. The immune system plays a key role in the development of this complex condition by triggering a systemic inflammatory response, which impairs regeneration in mammals. By contrast, zebrafish (Danio rerio) possess a remarkable regenerative capacity, recovering their swimming behaviour following a spinal cord injury (SCI). It is known that the immune system is a crucial player during tissue regeneration. However, the role of neutrophils, which are the first leukocytes to be recruited to the injury site, remains vastly unexplored. Therefore, the aim of this study was to understand whether neutrophils play an essential role in spinal cord regeneration in zebrafish larvae, a very useful model for biomedical studies. In the current study, it is shown that neutrophils are early recruited to the injury site, leaving gradually over time. Moreover, the main chemokines involved in the recruitment and resolution of the neutrophilic inflammatory process are upregulated in the used SCI model. In addition, this neutrophil dynamic can be modulated causing subsequent effects in the regenerative process. For instance, when neutrophil recruitment is delayed, defects in axonal regrowth, which lead to further impaired regeneration, were observed. Conversely, when neutrophilic inflammation resolution is accelerated, larvae show an improved axonal regrowth and an earlier recovery of the swimming capacity. Taken together, these results show that neutrophils are key players in defining the regenerative outcome following SCI, adding to the growing evidence on their beneficial role in tissue regeneration.