Suppression of fibrotic scar formation promotes axonal regeneration without disturbing blood-brain barrier repair and withdrawal of leukocytes after traumatic brain injury

The Journal of Comparative Neurology
Nozomu YoshiokaHitoshi Kawano

Abstract

The fibrotic scar containing type IV collagen (Col IV) formed in a lesion site is considered as an obstacle to axonal regeneration, because intracerebral injection of 2,2'-dipyridyl (DPY), an inhibitor of Col IV triple-helix formation, suppresses fibrotic scar formation in the lesion site and promotes axonal regeneration. To determine the role of the fibrotic scar on the healing process of injured central nervous system (CNS), the restoration of blood-brain barrier (BBB) and withdrawal of inflammatory leukocytes were examined in mice subjected to unilateral transection of the nigrostriatal dopaminergic pathway and intracerebral DPY injection. At 5 days after injury, destruction of BBB represented by leakage of Evans blue (EB) and widespread infiltration of CD45-immunoreactive leukocytes was observed around the lesion site, whereas reactive astrocytes increased surrounding the BBB-destroyed area. By 2 weeks after injury, the region of EB leakage and the diffusion of leukocytes were restricted to the inside of the fibrotic scar, and reactive astrocytes gathered around the fibrotic scar. In the DPY-treated lesion site, formation of the fibrotic scar was suppressed (84% decrease in Col IV-deposited area), reactive astrocytes occupi...Continue Reading

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Citations

Mar 1, 2012·Cell and Tissue Research·Hitoshi KawanoGeoffrey Raisman
Jan 28, 2014·Neuron·Joshua E Burda, Michael V Sofroniew
Jul 17, 2016·BMC Neuroscience·Kathleen K KellyJulie A Siegenthaler
Oct 28, 2016·Brain Research Bulletin·Dan LiHong-Peng Li
Mar 18, 2016·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Mariano Guardia Clausi, Steven W Levison
Jan 24, 2017·Journal of Tissue Engineering and Regenerative Medicine·Moonhang KimByung Hyune Choi
May 2, 2018·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Pietro G Di SummaSrinivas Madduri
Jun 2, 2020·Frontiers in Neuroscience·Noelia Esteban-GarciaLeyre Sánchez-Sánchez-Rojas
Feb 3, 2021·Nature Neuroscience·Cayce E DorrierRichard Daneman
Oct 17, 2020·Neural Regeneration Research·Zhuo ZhangDan Li
May 5, 2021·Stroke; a Journal of Cerebral Circulation·Lingling Xu, Yao Yao
Mar 26, 2021·Tissue Engineering. Part a·Ahad M SiddiquiNicolas N Madigan
Jun 8, 2021·Frontiers in Immunology·Colleen N BodnarAdam D Bachstetter

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