Neuronal damage in rat brain and spinal cord after cardiac arrest and massive hemorrhagic shock.
OBJECTIVE
Severe global ischemia often results in severe damage to the central nervous system of survivors. Hind-limb paralysis is a common deficit caused by global ischemia. Until recently, most studies of global ischemia of the central nervous system have examined either the brain or spinal cord, but not both. Spinal cord damage specifically after global ischemia has not been studied in detail. Because the exact nature of the neuronal damage to the spinal cord and the differences in neuronal damage between the brain and spinal cord after global ischemia are poorly understood, we developed a new global ischemia model in the rat and specifically studied spinal cord damage after global ischemia. Further, we compared the different forms of neuronal damage between the brain and spinal cord after global ischemia.


METHODS
Randomized, controlled study using three different global ischemia models in the rat.


METHODS
University research laboratory.


METHODS
Male, adult Sprague-Dawley rats (300 g).


METHODS
Animals were divided into three experimental groups, group A (n = 6, survived for 7 days), 12 mins of hemorrhagic shock; group B (n = 6, survived for 7 days), 5 mins of cardiac arrest; or group C (n = 6, each for 6 hrs, 12 hrs, 1 day, 3 days, and 7 days), 7 mins of hemorrhagic shock and 5 mins of cardiac arrest. Motor deficit of the hind limbs was studied 6 hrs to 7 days after resuscitation. Also, nonoperated animals (n = 6) were used as the control. Histologic analysis (hematoxylin and eosin, Fluoro-Jade B, terminal deoxynucleotidyl transferase- mediated dUTP end-labeling [TUNEL], Klüver-Barrera) and ultrastructural analysis using electron microscopy were performed on samples from the CA1 region of the hippocampus and lumbar spinal cord. Demyelination of the white matter of the lumbar spinal cord was analyzed semiquantitatively using Scion Image software.


RESULTS
No paraplegic animals were observed in either group A or B. All group C animals showed severe hind-limb paralysis. Severe neuronal damage was found in the CA1 region of the hippocampus in all groups, and the state of delayed neuronal cell death was similar among the three groups. Neuronal damage in the lumbar spinal cord was detected only in group C animals, mainly in the dorsal horn and intermediate gray matter. Demyelination was prominent in the ventral and ventrolateral white matter in group C. A significant difference was observed between control and group C rats with Scion Image software. Ultrastructural analysis revealed extensive necrotic cell death in the intermediate gray matter in the lumbar spinal cord in group C rats.


CONCLUSIONS
The combination in the global ischemia model (i.e., hemorrhagic shock followed by cardiac arrest) caused severe neuronal damage in the central nervous system. Thereby, hind-limb paralysis after global ischemia might result from spinal cord damage. These results suggest that therapeutic strategies for preventing spinal cord injury are necessary when treating patients with severe global ischemia.
Kudo
Yoshifumi
Y
Department of Anatomy, Showa University School of Medicine, Tokyo, Japan.
Ohtaki
Hirokazu
H
Dohi
Kenji
K
Yin
Li
L
Nakamachi
Tomoya
T
Endo
Sakura
S
Yofu
Sachiko
S
Hiraizumi
Yutaka
Y
Miyaoka
Hideyo
H
Shioda
Seiji
S
D000818:Animals; D016923:Cell Death; D003711:Demyelinating Diseases / Q000473:pathology; D004195:Disease Models, Animal; D006323:Heart Arrest / Q000150:complications*; D006614:Hindlimb / Q000294:innervation; D006624:Hippocampus / Q000473:pathology; D002534:Hypoxia, Brain / Q000209:etiology / Q000473:pathology*; D008159:Lumbar Vertebrae / Q000473:pathology; D008297:Male; D009048:Motor Skills; D009336:Necrosis / Q000473:pathology; D009474:Neurons / Q000473:pathology*; D010264:Paraplegia / Q000209:etiology / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000150:complications*; D020760:Spinal Cord Ischemia / Q000209:etiology / Q000473:pathology*