Reactive astrogliosis after spinal cord injury-beneficial and detrimental effects

Abstract

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.