An evaluation of white matter injury after spinal cord ischemia in rats: a comparison with gray matter injury.
We quantitatively assessed both gray and white matter injury after spinal cord ischemia in rats, and the relationship between the magnitude of gray and white matter injury was determined. Twenty-five male rats were anesthetized with isoflurane, and spinal cord ischemia (SCI) was induced by balloon intraaortic occlusion combined with hypotension. The animals were randomly allocated to one of the following three groups: animals with SCI for 12 min (SCI-12; n = 8), 15 min (SCI-15; n = 9), or those with sham operation (n = 8). Twenty-four hours after reperfusion, hindlimb motor function was assessed using the Basso-Beattie-Bresnahan scale scoring. Gray matter damage was assessed on the basis of the number of normal neurons in the ventral horn. White matter damage was assessed on the basis of the extent of vacuolation and amyloid precursor protein immunoreactivity in the ventral and ventrolateral white matter. There were significantly less normal neurons in the SCI-15 group compared with those in the SCI-12 and sham groups (P < 0.05). There was a significant positive correlation between the Basso-Beattie-Bresnahan scores and the number of normal neurons. The percentages of vacuolation areas in the SCI-15 group were significantly larger compared with those in the SCI-12 and sham groups (30% +/- 10% versus 9% +/- 7%, 0% +/- 0%, P < 0.05). Immunohistochemical analysis revealed increased amyloid precursor protein immunoreactivity in the swollen axons, especially in the SCI-15 group. There was a significant negative correlation between the number of normal neurons and percentages of vacuolation areas. These results indicate that both gray and white matter were injured after SCI in rats and the degree of white mater injury was correlated with the severity of gray matter injury after a relatively short recovery period.
Kurita
Naoko
N
Departments of Anesthesiology and Pathology, Nara Medical University, Kashihara, Nara, Japan.
Kawaguchi
Masahiko
M
Horiuchi
Toshinori
T
Inoue
Satoki
S
Sakamoto
Takanori
T
Nakamura
Mitsutoshi
M
Konishi
Noboru
N
Furuya
Hitoshi
H
D016564:Amyloid beta-Protein Precursor / Q000032:analysis; D000818:Animals; D001794:Blood Pressure; D001812:Blood-Brain Barrier; D001921:Brain / Q000473:pathology*; D007150:Immunohistochemistry; D007511:Ischemia / Q000473:pathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000098:blood supply*
D016564:Amyloid beta-Protein Precursor
Svensson LG, Crawford ES, Hess KR, et al. Experience with 1509 patients undergoing thoracoabdominal aortic operation. J Vasc Surg 1993;17:357–70.
Wan IYP, Angelini GD, Bryan AJ, et al. Prevention of spinal cord ischemia during descending thoracic and thoracoabdominal aortic surgery. Eur J Cardiothorac Surg 2001;19:203–13.
Coselli JS, LeMaire SA, Conklin LD, et al. Morbidity and mortality after extent II thoracoabdominal aortic aneurysm repair. Ann Thorac Surg 2002;73:1107–16.
Derrow AE, Seeger JM, Dame DA, et al. The outcome in the United States after thoracoabdominal aortic aneurysm repair, renal artery bypass, and mesenteric revascularization. J Vasc Surg 2001;34:54–61.
Juvonen T, Biancari F, Rimpiläinen J, et al. Strategies for spinal cord protection during descending thoracic and thoracoabdominal aortic surgery: up-to-date experimental and clinical results—a review. Scand Cardiovasc J 2002;36:136–60.
de Haan P, Kalkman CJ, Jacobs MJ. Pharmacologic neuroprotection in experimental spinal cord ischemia: a systematic review. J Neurosurg Anesthesiol 2001;13:3–12.
Matsumoto M, Iida Y, Sakabe T, et al. Mild and moderate hypothermia provide better protection than a burst-suppression dose of thiopental against ischemic spinal cord injury in rabbits. Anesthesiology 1997;86:1120–7.
Kakinohana M, Taira Y, Marsala M. The effect of graded postischemic spinal cord hypothermia on neurological outcome and histopathology after transient spinal ischemia in rat. Anesthesiology 1999;90:789–98.
Lips J, de Haan P, Bodewits P, et al. Neuroprotective effects of riluzole and ketamine during transient spinal cord ischemia in the rabbit. Anesthesiology 2000;93:1303–11.
Follis F, Scremin OU, Blisard KS, et al. Selective vulnerability of white matter during spinal cord ischemia. J Cereb Blood Flow Metab 1993;13:170–8.
Blisard KS, Follis F, Wong R, et al. Degeneration of axons in the corticospinal tract secondary to spinal cord ischemia in rats. Paraplegia 1995;33:136–40.
Kanellopoulos GK, Xu XM, Hsu CY, et al. White matter injury in spinal cord ischemia: protection by AMPA/kainate glutamate receptor antagonism. Stroke 2000;31:1945–52.
Taira Y, Marsala M. Effect of proximal arterial perfusion pressure on function, spinal cord blood flow, and histopathologic changes after increasing intervals of aortic occlusion in the rat. Stroke 1996;27:1850–8.
Basso DM, Beattie MS, Bresnahan JC. A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma 1995;12:1–21.
Pantoni L, Garcia JH, Gutierrez JA. Cerebral white matter is highly vulnerable to ischemia. Stroke 1996;27:1641–7.
Dietrich WD, Kraydieh S, Prado R, et al. White matter alterations following thromboembolic stroke: a beta-amyloid precursor protein immunocytochemical study in rats. Acta Neuropathol 1998;95:524–31.
Kalaria RN, Bhatti SU, Palatinsky EA, et al. Accumulation of the beta amyloid precursor protein at sites of ischemic injury in rat brain. Neuroreport 1993;4:211–4.
Stephenson DT, Rash K, Clemens JA. Amyloid precursor protein accumulates in regions of neurodegeneration following focal cerebral ischemia in the rat. Brain Res 1992;393:128–35.
Yam PS, Patterson J, Graham DI, et al. Topographical and quantitative assessment of white matter injury following a focal ischemic lesion in the rat brain. Brain Res Brain Res Protoc 1998;2:315–22.
Valeriani V, Dewar D, McCulloch J. Quantitative assessment of ischemic pathology in axons, oligodendrocytes, and neurons: attenuation of damage after transient ischemia. J Cereb Blood Flow Metab 2000;20:765–71.
Imai H, McCulloch J, Graham DI, et al. New method for the quantitative assessment of axonal damage in focal cerebral ischemia. J Cereb Blood Flow Metab 2002;22:1080–9.
Westergren H, Yu WR, Farooque M, et al. Systemic hypothermia following spinal cord compression injury in the rat: axonal changes studied by beta-APP, ubiquitin, and PGP 9.5 immunohistochemistry. Spinal Cord 1999;37:696–704.
Yam PS, Takasago T, Dewar D, et al. Amyloid precursor protein accumulates in white matter at the margin of a focal ischaemic lesion. Brain Res 1997;760:150–7.
Kato H, Kanellopoulos GK, Matsuo S, et al. Neuronal apoptosis and necrosis following spinal cord ischemia in the rat. Exp Neurol 1997;148:464–74.
Kawaguchi M, Kimbro JR, Drummond JC, et al. Isoflurane delays but does not prevent cerebral infarction in rats subjected to focal ischemia. Anesthesiology 2000;92:1335–42.
Sakamoto T, Kawaguchi M, Kurita N, et al. Long-term assessment of hind limb motor function and neuronal injury following spinal cord ischemia in rats. J Neurosurg Anesthesiol 2003;15:104–9.