Delayed death of identified reticulospinal neurons after spinal cord injury in lampreys.
There is controversy about whether axotomized neurons undergo death or only severe atrophy after spinal cord injury (SCI) in mammals. Lampreys recover from complete spinal transection, but only about half of the severed spinal-projecting axons regenerate through the site of injury. The fates of the unregenerated neurons remain unknown, and until now death of axotomized spinal-projecting neurons has not been described in the lamprey brain. We now report that in animals allowed to survive for 12 or more weeks after spinal cord transection, several identified reticulospinal (RS) neurons were missing in Nissl-stained or neurofilament-immunostained brain whole mounts. At earlier times, these neurons were swollen and pale in Nissl-stained preparations. Retrograde fluorescent labeling from the site of transection combined with TUNEL histochemistry suggested that neuronal death, including that of the identified RS neurons, began in animals 4 weeks posttransection, reaching a peak at 12-16 weeks. This was not seen in untransected animals. The TUNEL positivity suggests that some cells were dying by apoptosis. Of special interest, among the identified neurons, this delayed cell death was restricted to neurons that at earlier posttransection times have a low probability of regeneration. These data show that SCI induces delayed cell death in lamprey spinal-projecting neurons and suggest that the reason why some neurons are "bad regenerators" is that they are already undergoing apoptotic cell death. Thus protection from apoptosis may be necessary in order to enhance axonal regeneration after SCI.
Shifman
M I
MI
Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. mshifman@mail.med.upenn.edu
Zhang
G
G
Selzer
M E
ME
D000818:Animals; D019771:Axotomy; D016923:Cell Death; D004525:Efferent Pathways / Q000033:anatomy & histology*; D020287:In Situ Nick-End Labeling; D007798:Lampreys / Q000033:anatomy & histology*; D009416:Nerve Regeneration; D009474:Neurons / Q000166:cytology*; D012154:Reticular Formation / Q000033:anatomy & histology*; D013116:Spinal Cord / Q000166:cytology / Q000473:pathology; D013119:Spinal Cord Injuries / Q000473:pathology*