Autonomic and motor neuron death is progressive and parallel in a lumbosacral ventral root avulsion model of cauda equina injury.
Injuries to the cauda equina of the spinal cord result in autonomic and motor neuron dysfunction. We developed a rodent lumbosacral ventral root avulsion injury model of cauda equina injury to investigate the lesion effect in the spinal cord. We studied the retrograde effects of a unilateral L5-S2 ventral root avulsion on efferent preganglionic parasympathetic neurons (PPNs) and pelvic motoneurons in the L6 and S1 segments at 1, 2, 4, and 6 weeks postoperatively in the adult male rat. We used Fluoro-Gold-prelabeling techniques, immunohistochemistry, and quantitative stereologic analysis to show an injury-induced progressive and parallel death of PPNs and motoneurons. At 6 weeks after injury, only 22% of PPNs and 16% of motoneurons remained. Furthermore, of the neurons that survived at 6 weeks, the soma volume was reduced by 25% in PPNs and 50% in motoneurons. Choline acetyltransferase (ChAT) protein was expressed in only 30% of PPNs, but 80% of motoneurons remaining at 1 week postoperatively, suggesting early differential effects between these two neuronal types. However, all remaining PPNs and motoneurons were ChAT positive at 4 weeks postoperatively. Nuclear condensation and cleaved caspase-3 were detected in axotomized PPNs and motoneurons, suggesting apoptosis as a contributing mechanism of the neural death. We conclude that lumbosacral ventral root avulsions progressively deplete autonomic and motor neurons. The findings suggest that early neuroprotection will be an important consideration in future attempts of treating acute cauda equina injuries.
Hoang
Thao X
TX
Department of Neurology and Brain Research Institute, David Geffen School of Medicine at University of California--Los Angeles, Los Angeles, California 90095, USA.
Nieto
Jaime H
JH
Tillakaratne
Niranjala J K
NJ
Havton
Leif A
LA
D000818:Animals; D017776:Autonomic Pathways / Q000378:metabolism / Q000473:pathology*; D006690:Bisbenzimidazole / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002452:Cell Count; D016923:Cell Death; D002467:Cell Nucleus / Q000378:metabolism; D048429:Cell Size; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004195:Disease Models, Animal; D005456:Fluorescent Dyes / Q000378:metabolism; D007150:Immunohistochemistry; D007796:Laminectomy / Q000379:methods; D008161:Lumbosacral Region / Q000473:pathology; D008297:Male; D009046:Motor Neurons / Q000473:pathology*; D011128:Polyradiculopathy / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000473:pathology*; D013266:Stilbamidines / Q000378:metabolism; D013997:Time Factors
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D005456:Fluorescent Dyes; D013266:Stilbamidines; D002795:Choline O-Acetyltransferase; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D006690:Bisbenzimidazole