H. Kato et al., PROTECTION OF RAT SPINAL-CORD FROM ISCHEMIA WITH DEXTRORPHAN AND CYCLOHEXIMIDE - EFFECTS ON NECROSIS AND APOPTOSIS, Journal of thoracic and cardiovascular surgery, 114(4), 1997, pp. 609-618
Objective: We examined the characteristics of neuronal cell death afte
r transient spinal cord ischemia in the rat and the effects of an N-me
thyl-D-aspartate antagonist, dextrorphan, and a protein synthesis inhi
bitor, cycloheximide, Methods: Spinal cord ischemia was induced for 15
minutes in Long-Evans rats with use of a 2F Fogarty catheter, which w
as passed through the left carotid artery and occluded the descending
aorta, combined with a blood volume reduction distal to the occlusion,
The rats were killed after 1, 2, and 7 days, Other groups of rats wer
e pretreated with dextrorphan (30 mg/kg, intraperitoneally, n = 7), cy
cloheximide (30 mg, intrathecally, n = 7), or vehicle (saline solution
, n = 12) and killed after 2 days, Results: This model reliably produc
ed paraplegia and histopathologically distinct morphologic changes con
sistent with necrosis or apoptosis by light and electron microscopic c
riteria in different neuronal populations in the lumbar cord, Scattere
d necrotic neurons were seen in the intermediate gray matter (laminae
3 to 7) after 1, 2, and 7 days, whereas apoptotic neurons were seen in
the dorsal horn laminae 1 to 3 after 1 and 2 days, Deoxyribonucleic a
cid extracted from lumbar cord showed internucleosomal fragmentation (
laddering) on gel electrophoresis indicative of apoptosis, The severit
y of paraplegia in the rats treated with dextrorphan and cycloheximide
was attenuated 1 day and 2 days after ischemia, The numbers of both n
ecrotic and apoptotic neurons were markedly reduced in both dextrorpha
n- and cycloheximide-treated rats. Conclusions: The results suggest th
at both N-methyl-D-aspartate receptor-mediated excitotoxicity and apop
tosis contribute to spinal cord neuronal death after ischemia and that
pharmacologic treatments directed at blocking both of these processes
may have therapeutic utility in reducing spinal cord ischemic injury.