Selective Vulnerability of White Matter during Spinal Cord Ischemia

Abstract

The long-term effects of spinal cord ischemia were studied in 21 rats by lesion scores (LS, n = 21), somatosensory evoked potentials (SEP, n = 16), electromyographic measurements (EMG, n = 12) and histology of the spinal cord (n = 21) 48.5 +/- 57.2 days after 10- to 12-min occlusion of the thoracic aorta and subclavian arteries. All the animals were initially paraplegic with a spastic presentation but seven recovered within 2 days (group A), demonstrating low LS (3.4 +/- 1.05) normal EMGs (n = 3) and unremarkable histology. The 14 paraplegic animals presented relevant findings of the lumbar cord consisting of white matter lesions only (group B, n = 7) or white and gray matter lesions (group C, n = 7). Group B animals showed severe deficit (LS = 11.8 +/- 2.93) without denervation on EMG (n = 5) or muscle atrophy on histology. Group C animals displayed equal impairment (LS = 14.4 +/- 0.71), denervation on EMG (n = 4), and muscle atrophy. Resting motor unit activity of groups B and C were significantly different from group A (p < 0.001), while LS of groups B and C did not differ (p = 0.083). These data underscore the nature and the extent of white matter lesions during spinal cord ischemia, a finding which has generally been eclipsed by emphasis on gray matter lesions in previous studies.

The N -Methyl- d -Aspartate Antagonist CNS 1102 Protects Cerebral Gray and White Matter From Ischemic Injury Following Temporary Focal Ischemia in Rats

“…Although studies have demonstrated that white matter is susceptible to ischemic injury, the mechanisms of white matter injury are not well characterized. 7,14 In contrast to gray matter ischemia, in vitro studies suggest that activation of glutamate receptors may not be a key event in the mediation of ischemic cerebral white matter injury. Recent studies suggested some possible explanations for ischemic white matter injury.…”

White Matter Injury in Spinal Cord Ischemia

“…Descriptions of morphological changes in the white matter of the rat spinal cord 1 to 2 months after transient ischemia have been previously reported. 8,24 In one of these studies, degenerating axons containing aggregates of microtubules and dense bodies, disintegrating myelin sheaths, and scavenger cells were seen in the corticospinal tract of the lumbar cord 32 days after injury. 23 The postischemic loss of axons in the white mater of the 4th lumbar spinal cord segment may have resulted from local axonal injury or from a lesion in the more proximal axonal segments up to their cell bodies.…”

“…The conventional view that the white matter is less vulnerable to ischemic injury as compared with the gray matter is now being questioned. Increasing in vivo evidence indicates that ischemia may primarily damage white matter in the spinal cord 8 and the brain. 9,10 Whereas excitotoxins play a major role in the pathogenesis of ischemic gray matter injury, 4 the role of glutamate receptor action in ischemic white matter lesion is less clear.…”

Spinal Cord Ischemia

“…After 9 minutes of occlusion, motor dysfunction was severe, but it was reversible at 2 days. Pathology was limited to intermediate gray and dorsal horns predominantly, [17][18][19][20][21] with preservation of anterior horns. After occlusion for 11 minutes, neurological deficits were severe, with persistent paraplegia.…”

“…[1][2][3][4][5][6][7][8][9][10] Animal models of spinal cord ischemia have been described in the literature with variable reproducibility. [11][12][13][14][15][16][17][18][19][20][21] Zivin et al 15,16 developed a highly reproducible model in the rabbit that has become the standard for the study of experimental spinal cord ischemia. In the rabbit, transient occlusion of the infrarenal segment of aorta causes…”