Wang Ruizhong, King Tamara, Ossipov Michael H, Rossomando Anthony J, Vanderah Todd W, Harvey Pamela, Cariani Peter, Frank Eric, Sah Dinah W Y, Porreca Frank
Department of Pharmacology, University of Arizona, College of Medicine, 1501 N Campbell Avenue, Tucson, Arizona 85724-5050, USA.
Nat Neurosci. 2008 Apr;11(4):488-96. doi: 10.1038/nn2069. Epub 2008 Mar 23.
Dorsal root injury results in substantial and often irreversible loss of sensory functions as a result of the limited regenerative capacity of sensory axons and the inhibitory barriers that prevent both axonal entry into and regeneration in the spinal cord. Here, we describe previously unknown effects of the growth factor artemin after crush injury of the dorsal spinal nerve roots in rats. Artemin not only promoted re-entry of multiple classes of sensory fibers into the spinal cord and re-establishment of synaptic function and simple behavior, but it also, surprisingly, promoted the recovery of complex behavior. These effects occurred after a 2-week schedule of intermittent, systemic administration of artemin and persisted for at least 6 months following treatment, suggesting a substantial translational advantage. Systemic artemin administration produced essentially complete and persistent restoration of nociceptive and sensorimotor functions, and could represent a promising therapy that may effectively promote sensory neuronal regeneration and functional recovery after injury.
背根损伤会导致感觉功能大量丧失,且常常不可逆转,这是因为感觉轴突的再生能力有限,以及存在抑制性屏障,这些屏障既阻止轴突进入脊髓,也阻止其在脊髓中再生。在此,我们描述了生长因子Artemin在大鼠背侧脊神经根挤压伤后的一些此前未知的作用。Artemin不仅促进了多类感觉纤维重新进入脊髓,并重建了突触功能和简单行为,而且令人惊讶的是,它还促进了复杂行为的恢复。这些作用在间歇性全身给予Artemin两周后出现,并在治疗后持续至少6个月,这表明具有显著的转化优势。全身给予Artemin可基本实现伤害性感受和感觉运动功能的完全且持久恢复,可能代表一种有前景的疗法,可有效促进损伤后感觉神经元的再生和功能恢复。