Department of Developmental Biology, Washington University School of Medicine, Saint Louis, MO, USA.
Adv Neurobiol. 2024;39:213-231. doi: 10.1007/978-3-031-64839-7_9.
Spinal cord injuries cause irreversible loss of sensory and motor functions. In mammals, intrinsic and extrinsic inhibitions of neuronal regeneration obstruct neural repair after spinal cord injury. Although astrocytes have been involved in a growing list of vital homeostatic functions in the nervous system, their roles after injury have fascinated and puzzled scientists for decades. Astrocytes undergo long-lasting morphological and functional changes after injury, referred to as reactive astrogliosis. Although reactive astrogliosis is required to contain spinal cord lesions and restore the blood-spinal cord barrier, reactive astrocytes have detrimental effects that inhibit neuronal repair and remyelination. Intriguingly, elevated regenerative capacity is preserved in some non-mammalian vertebrates, where astrocyte-like glial cells display exclusively pro-regenerative effects after injury. A detailed molecular and phenotypic catalog of the continuum of astrocyte reactivity states is an essential first step toward the development of glial cell manipulations for spinal cord repair.
脊髓损伤会导致感觉和运动功能的不可逆转丧失。在哺乳动物中,神经元再生的内在和外在抑制阻碍了脊髓损伤后的神经修复。尽管星形胶质细胞在神经系统的许多重要的稳态功能中发挥作用,但它们在损伤后的作用几十年来一直令科学家着迷和困惑。星形胶质细胞在损伤后会发生持久的形态和功能变化,称为反应性星形胶质增生。尽管反应性星形胶质增生是为了控制脊髓损伤并恢复血脊髓屏障所必需的,但反应性星形胶质细胞具有抑制神经元修复和髓鞘再生的有害作用。有趣的是,在一些非哺乳动物的脊椎动物中,再生能力得以保留,其中星形胶质细胞样胶质细胞在损伤后仅表现出促进再生的作用。详细的分子和表型图谱描绘了星形胶质细胞反应性状态的连续体,这是开发用于脊髓修复的胶质细胞操作的重要第一步。