The characteristics of neuronal injury in a static compression model of spinal cord injury in adult rats.
Studies of spinal cord injury using contusion (impact) injury paradigms have shown that neuronal death is an acute event that is largely over within 24 h. However, much less is known about cell death following compression injury, despite compression being a key component of natural spinal injuries. We have therefore used neuronal nuclei (NeuN) immunostaining to examine the spatiotemporal pattern of neuronal loss after static compression injury in adult rats. 3D reconstruction was used to reveal the full effect of the injury. Neuronal loss at the injury epicentre, assessed by NeuN immunostaining, amounted to 44% at 1 day but increased to 73% at 3 days and 81% at 1 month. Neuronal loss was also seen 5 mm rostral and caudal to the epicentre, but was not significant until 3 days. NeuN loss was greatest in the ventral horns and in the intermediate grey matter, with the lateral dorsal horns relatively spared. Cystic cavities formed after injury, but were not evident until 4 weeks and were small in size. In contrast to the slow profile of neuronal loss, the compression injury also evoked a transient expression of activating transcription factor-3 (ATF3) and activated c-Jun in neurons. ATF3 expression peaked at 3 days and declined at 7 days. Our spatiotemporal analysis of compression injury shows that neuronal loss is much more protracted than in contusion injury, and highlights the potential for neuroprotective strategies. This study is also the first indication of ATF3 involvement in spinal cord injury.
Huang
W L
WL
Neuroscience Centre, Institute of Cell and Molecular Science, Queen Mary University of London, UK. w.huang@qmul.ac.uk
George
K J
KJ
Ibba
V
V
Liu
M C
MC
Averill
S
S
Quartu
M
M
Hamlyn
P J
PJ
Priestley
J V
JV
D051700:Activating Transcription Factor 3 / Q000378:metabolism; D000818:Animals; D016923:Cell Death / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D021621:Imaging, Three-Dimensional / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D007796:Laminectomy / Q000379:methods; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013117:Spinal Cord Compression / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D013997:Time Factors
D051700:Activating Transcription Factor 3; C497108:Atf3 protein, rat; D016755:Proto-Oncogene Proteins c-jun; D010751:Phosphopyruvate Hydratase