The multimolecular cascade of spinal cord injury. Studies on prostanoids, calcium, and proteinases.
Experimental spinal cord injury in animals induced by weight drop produces neurological deficit and paralysis. Correlation of the progressive morphological changes in the lesion by both light and electron microscopy with the biochemical alterations revealed ischemia, edema, hemorrhage, tissue necrosis, granular changes in axons, vesicular degeneration of myelin and axonal calcification. The biochemical pathology was that of degradation of axonal (neurofilaments) and myelin proteins (MBP and PLP) with increased activities of proteolytic enzymes and particularly the neutral proteinase. The level of total calcium increased progressively in the lesion to a peak at 8 hrs. and subsequently remained constant thereafter. The capacity of calcium for activating proteinases and lipases and fostering the degradation of axon and myelin proteins as well as the liberation of arachidonic acid required for the synthesis of prostanoids must be relevant. An increased production of prostanoids is indicated by elevation of thromboxane (TxB2), a stable metabolite of TXA2 at 1 hour after injury. The 6-keto-PG1(1)a was also increased but to a lesser extent. We suspect that the activation of arachidonic acid metabolism contributes to post-traumatic vascular injury and the progressive ischemia. These putative roles for calcium in proteolysis and lipolysis, inducing degradation of macromolecules and production of prostanoids which initiate edema, lysolecithin a myelinolytic factor and mitochondrial dysfunction in spinal cord injury are discussed.
Banik
N L
NL
Department of Neurology, Medical University of South Carolina, Charleston 29425.
Hogan
E L
EL
Hsu
C Y
CY
D002118:Calcium / Q000502:physiology*; D010450:Endopeptidases / Q000502:physiology*; D005227:Fatty Acids / Q000502:physiology*; D006801:Humans; D011466:Prostanoic Acids / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000201:enzymology / Q000503:physiopathology*
D005227:Fatty Acids; D011466:Prostanoic Acids; D010450:Endopeptidases; D002118:Calcium