The review by Jerry Silver and Jared H. Miller discusses the role of the glial scar in inhibiting axon regeneration in the adult central nervous system (CNS). The glial scar, primarily composed of reactive astrocytes and proteoglycans, forms after CNS injury and acts as a physical barrier that prevents axons from crossing the lesion site. Chondroitin and keratan sulfate proteoglycans are key inhibitory molecules produced by reactive astrocytes, contributing to the failure of axon regeneration. The authors explore the mechanisms by which these molecules inhibit axon growth, including their role in growth cone collapse and the formation of dystrophic endings. They also highlight the potential benefits of the glial scar, such as stabilizing the CNS tissue and repairing the blood-brain barrier (BBB). The review further examines the differential responses of axons to the glial scar, with some axons capable of regenerating despite the inhibitory environment. Strategies to enhance regeneration, such as modifying proteoglycans and blocking myelin inhibitors, are discussed. The authors conclude that a combination of treatments, including removing extrinsic inhibitors and enhancing intrinsic growth potential, may be necessary to achieve long-distance and functional regeneration after CNS injury.The review by Jerry Silver and Jared H. Miller discusses the role of the glial scar in inhibiting axon regeneration in the adult central nervous system (CNS). The glial scar, primarily composed of reactive astrocytes and proteoglycans, forms after CNS injury and acts as a physical barrier that prevents axons from crossing the lesion site. Chondroitin and keratan sulfate proteoglycans are key inhibitory molecules produced by reactive astrocytes, contributing to the failure of axon regeneration. The authors explore the mechanisms by which these molecules inhibit axon growth, including their role in growth cone collapse and the formation of dystrophic endings. They also highlight the potential benefits of the glial scar, such as stabilizing the CNS tissue and repairing the blood-brain barrier (BBB). The review further examines the differential responses of axons to the glial scar, with some axons capable of regenerating despite the inhibitory environment. Strategies to enhance regeneration, such as modifying proteoglycans and blocking myelin inhibitors, are discussed. The authors conclude that a combination of treatments, including removing extrinsic inhibitors and enhancing intrinsic growth potential, may be necessary to achieve long-distance and functional regeneration after CNS injury.