氧化应激
DNA损伤
视神经
细胞凋亡
瓦勒氏变性
变性(医学)
病理
少突胶质细胞
细胞生物学
生物
医学
解剖
髓鞘
神经科学
DNA
中枢神经系统
内分泌学
遗传学
作者
Lillian M. Toomey,Melissa Papini,Thomas Clarke,Alexander J. Wright,Eleanor M Denham,Andrew Warnock,Terry McGonigle,Carole A. Bartlett,Melinda Fitzgerald,Chidozie C. Anyaegbu
摘要
Optic nerve injury causes secondary degeneration, a sequela that spreads damage from the primary injury to adjacent tissue, through mechanisms such as oxidative stress, apoptosis, and blood-brain barrier (BBB) dysfunction. Oligodendrocyte precursor cells (OPCs), a key component of the BBB and oligodendrogenesis, are vulnerable to oxidative deoxyribonucleic acid (DNA) damage by 3 days post-injury. However, it is unclear whether oxidative damage in OPCs occurs earlier at 1 day post-injury, or whether a critical ‘window-of-opportunity’ exists for therapeutic intervention. Here, a partial optic nerve transection rat model of secondary degeneration was used with immunohistochemistry to assess BBB dysfunction, oxidative stress, and proliferation in OPCs vulnerable to secondary degeneration. At 1 day post-injury, BBB breach and oxidative DNA damage were observed, alongside increased density of DNA-damaged proliferating cells. DNA-damaged cells underwent apoptosis (cleaved caspase3+), and apoptosis was associated with BBB breach. OPCs experienced DNA damage and apoptosis and were the major proliferating cell type with DNA damage. However, the majority of caspase3+ cells were not OPCs. These results provide novel insights into acute secondary degeneration mechanisms in the optic nerve, highlighting the need to consider early oxidative damage to OPCs in therapeutic efforts to limit degeneration following optic nerve injury.
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