Paralysis following spinal cord injury(SCI) is due to failure of axonal regeneration. It is believed that the capacities of neurons to regrow their axons are due partly to their intrinsic characteristics, which in turn are greatly influenced by several types of inhibitory molecules that are present, or even increased in the extracellular environment of the injured spinal cord. Many of these inhibitory molecules have been studied extensively in recent years. It has been suggested that the small GTPase Rho A is an intracellular convergence point for signaling by these extracellular inhibitory molecules, but due to the complexity of the central nervous system(CNS) in mammals, and the limitation of pharmacological tools, the specific roles of Rho A are unclear. By exploiting the anatomical and technical advantages of the lamprey CNS, we recently demonstrated that Rho A knockdown promotes true axon regeneration through the lesion site after SCI. In addition, we found that Rho A knockdown protects the large, identified reticulospinal neurons from apoptosis after their axons were axotomized in spinal cord. Therefore, manipulation of the Rho A signaling pathway may be an important approach in the development of treatments that are both neuroprotective and axon regeneration-promoting, to enhance functional recovery after SCI. Paralysis following spinal cord injury (SCI) is due to failure of axonal regeneration. It is believed to the ability of neurons to regrow their axons are due partly to their intrinsic characteristics, which in turn are greatly influenced by several types of inhibitory molecules that are present, or even increased in the extracellular environment of the injured spinal cord. Many of these inhibitory molecules have been studied extensively in recent years. It has been suggested that the small GTPase Rho A is an intracellular convergence point for signaling by these extracellular inhibitory molecules , but due to the complexity of the central nervous system (CNS) in mammals, and the limitation of pharmacological tools, the specific roles of Rho A are unclear. By exploiting the anatomical and technical advantages of the lamprey CNS, we recently prototype that Rho A knockdown promotes true axon regeneration through the lesion site after SCI. In addition, we found that Rho A knockdown pr otects the large, identified reticulospinal neurons from apoptosis after their axons were axotomized in spinal cord. Therefore, manipulation of the Rho A signaling pathway may be an important approach in the development of treatments that are both neuroprotective and axon regeneration-promoting, to enhance functional recovery after SCI.