Preferential regeneration of spinal axons through the scar in hemisected lamprey spinal cord.
Axons of lamprey spinal cord can regenerate across a complete spinal transection. Thus, unlike the scar of injured mammalian spinal cords, the scar in the lamprey is not an absolute impediment to regeneration. However, it is still not known whether the scar is a relative impediment or whether it provides a favorable environment for regeneration compared to the spinal cord parenchyma. In order to answer this question, the cords of 12 large larval sea lampreys (4-5 years old) were hemisected at the level of the third gill and the animals allowed to recover for 10 weeks. The large reticulospinal neurons (Müller and Mauthner cells) or their giant axons were injected intracellularly with HRP and their regenerating neurites visualized in central nervous system (CNS) wholemounts. Forty-five of seventy-one regenerating neurites (64%) grew beyond the level of the hemisection. Of these, 36 (82%) regenerated through the scar and remained on the same side of the cord as their parent axons, while only 8 (18%) crossed the midline and grew around the scar. Thus, regenerating neurites of giant reticulospinal axons tended to grow through the hemisection scar rather than around it. Once they passed the level of injury, they continued to elongate in their appropriate paths. It is possible that this tendency for axons to regenerate through the scar reflects the greater amount of empty spaces on the hemisected side. In order to rule this out, 13 animals received contralateral simultaneous hemisections at the level of the 3rd and 7th gills. This procedure created large numbers of degenerating axons and potential empty spaces both rostral and caudal to the scars within both hemicords; 92 of 158 neurites (58%) regenerated beyond the level of their respective hemisections. All of these grew through the scar and none crossed to the contralateral side. Distal to either hemisection, neurites remained on their correct side regardless of whether the contralateral cord contained normal CNS parenchyma or axonal debris and empty spaces produced by Wallerian degeneration. Moreover, in hemisected and double hemisected animals, as well as in completely transected control animals, neurites regenerating in their correct direction grew further than those that were misrouted. Because lamprey spinal axons grow preferentially through a scar rather than around it, the scar may play a positive role in supporting axonal regeneration.
Lurie
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David Mahoney Institute of Neurological Sciences, University of Pennsylvania School of Medicine, Philadelphia 19104.
Selzer
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D000818:Animals; D001369:Axons / Q000502:physiology*; D001696:Biomechanical Phenomena; D002921:Cicatrix / Q000503:physiopathology*; D006735:Horseradish Peroxidase; D007798:Lampreys / Q000502:physiology*; D007814:Larva / Q000502:physiology; D008854:Microscopy, Electron; D009416:Nerve Regeneration / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology* / Q000648:ultrastructure
D006735:Horseradish Peroxidase