Regenerative Medicine Program, Departments of Physiology and Biochemistry and Medical Genetics, the Spinal Cord Research Center, University of Manitoba, Winnipeg, MB R3E 0J9, Canada.
Mol Neurobiol. 2012 Oct;46(2):251-64. doi: 10.1007/s12035-012-8287-4. Epub 2012 Jun 9.
Reactive astrogliosis is a pathologic hallmark of spinal cord injury (SCI). It is characterised by profound morphological, molecular, and functional changes in astrocytes that occur within hours of SCI and evolves as time elapses after injury. Astrogliosis is a defense mechanism to minimize and repair the initial damage but eventually leads to some detrimental effects. Reactive astrocytes secrete a plethora of both growth promoting and inhibitory factors after SCI. However, the production of inhibitory components surpasses the growth stimulating factors, thus, causing inhibitory effects. In severe cases of injury, astrogliosis results in the formation of irreversible glial scarring that acts as regeneration barrier due to the expression of inhibitory components such as chondroitin sulfate proteoglycans. Scar formation was therefore recognized from a negative perspective for many years. Accumulating evidence from pharmacological and genetic studies now signifies the importance of astrogliosis and its timing for spinal cord repair. These studies have advanced our knowledge regarding signaling pathways and molecular mediators, which trigger and modulate reactive astrocytes and scar formation. In this review, we discuss the recent advances in this field. We also review therapeutic strategies that have been developed to target astrocytes reactivity and glial scaring in the environment of SCI. Astrocytes play pivotal roles in governing SCI mechanisms, and it is therefore crucial to understand how their activities can be targeted efficiently to harness their potential for repair and regeneration after SCI.
反应性星形胶质细胞增生是脊髓损伤 (SCI) 的病理标志。它的特点是星形胶质细胞在 SCI 发生后数小时内发生深刻的形态、分子和功能变化，并随着损伤后时间的推移而演变。星形胶质细胞增生是一种防御机制，可最大程度地减轻和修复初始损伤，但最终会导致一些不利影响。SCI 后，反应性星形胶质细胞会分泌大量促进生长和抑制因子。然而，抑制性成分的产生超过了生长刺激因子，从而导致抑制作用。在严重的损伤情况下，星形胶质细胞增生导致不可逆的胶质瘢痕形成，由于抑制性成分（如软骨素硫酸盐蛋白聚糖）的表达，胶质瘢痕充当了再生障碍。因此，多年来，瘢痕形成一直被视为负面因素。药理学和遗传学研究的积累证据现在表明星形胶质细胞增生及其对脊髓修复的时机的重要性。这些研究提高了我们对触发和调节反应性星形胶质细胞和瘢痕形成的信号通路和分子介质的认识。在这篇综述中，我们讨论了该领域的最新进展。我们还回顾了针对 SCI 环境中星形胶质细胞反应性和胶质瘢痕的治疗策略。星形胶质细胞在控制 SCI 机制中起着关键作用，因此了解如何有效地靶向它们的活动以利用它们在 SCI 后的修复和再生潜力至关重要。
