Exp Neurol, 2008 · DOI: 10.1016/j.expneurol.2007.06.020 · Published: February 1, 2008
Axons often fail to regenerate after spinal cord injuries, posing a significant challenge in medicine and neuroscience. However, progress has been made in identifying inhibitory proteins in CNS myelin, leading to strategies that help axons overcome this inhibition. One successful strategy involves elevating intracellular cyclic AMP (cAMP), which promotes axonal regeneration in the central nervous system. This can be achieved through various methods like peripheral conditioning lesions, cAMP analogs, neurotrophin priming, or rolipram treatment. The effects of cAMP are transcription-dependent, activating CREB and upregulating genes like arginase I and interleukin-6, which directly aid axonal regeneration. Further research on cAMP-regulated genes and clinical trials of agents like rolipram could fully realize cAMP's therapeutic potential.
Rolipram, due to its efficacy in animal models and ability to cross the blood-brain barrier, should be considered a leading candidate for human clinical trials.
Identifying and studying additional cAMP-regulated genes may yield new agents capable of promoting axonal regeneration, potentially leading to more specific and effective therapies.
Combining cAMP-elevating strategies with other approaches, such as neurotrophin administration and cell transplantation, may enhance axonal regeneration and functional recovery after spinal cord injury.