Effects of Methylprednisolone and the Combination of α‐Tocopherol and Selenium on Arachidonic Acid Metabolism and Lipid Peroxidation in Traumatized Spinal Cord Tissue

Abstract

Traumatic injury of the spinal cord leads to a series of pathological events that result in tissue necrosis and paralysis. Among the earliest biochemical reactions are hydrolysis of fatty acids from membrane phospholipids, production of biologically active eicosanoids, and peroxidation of lipids. This study examines the effect of agents purported to improve recovery following spinal cord trauma, methylprednisolone sodium succinate (MPSS) and the combination of alpha-tocopherol and selenium (Se), on the posttraumatic alterations of membrane lipid metabolism. Pretreatment with either MPSS or alpha-tocopherol and Se reduced the trauma-induced release of total FFA including arachidonate in the injured spinal cord tissue. In addition, these agents decreased the postinjury levels of prostanoids. Pretreatment with either MPSS or alpha-tocopherol and Se also completely prevented the trauma-induced loss of cholesterol while inhibiting the increase of a cholesterol peroxidation product, 25-hydroxycholesterol. These data suggest that: perturbation of membrane lipid metabolism may contribute to the tissue necrosis and functional deficit of spinal cord injury and MPSS or the combination of alpha-tocopherol and Se may protect injured spinal cord tissue, at least in part, by limiting these posttraumatic membrane lipid changes.

Platelet aggregation in traumatic spinal cord injury

“…11 The products of membrane breakdown (including polyunsaturated fatty acids, prostanoids, leukotriens and free radicals), several cations, amino acids, monoamines, neuropeptides are proposed as injury factors. 12,13 Increased generation of free oxygen species and lipid peroxidation are early biochemical changes in central nervous system trauma. 13,14 It is suggested that chronic hypoventilation, activation of arachidonic acid metabolism, oxidation of extravasated hemoglobin, in®ltration and activation of macrophages and neutrophils are involved in the generation of free radicals.…”

Effect of postinjury intravenous or intrathecal methylprednisolone on spinal cord excitatory amino-acid release, nitric oxide generation, PGE2 synthesis, and myeloperoxidase content in a pig model of acute spinal cord injury

“…[18][19][20][21] One possible explanation for the differences in methylprednisolone's efficacy when comparing human and animal data is that in animal studies, methylprednisolone is almost invariably administered prior to spinal cord injury, or immediately after injury. [2][3][4]6 In contrast, in the human clinical situation, the time necessary for patient transport and work-up can delay methylprednisolone administration until many hours after the spinal cord injury. Consequently, it is unclear to what extent the experimental animal data can be extrapolated to the human clinical setting.…”

“…Multiple animal studies have shown that high-dose methylprednisolone treatment of acute spinal cord injury results in a reduction in biochemical mediators of secondary neurological injury [1][2][3][4][5][6] and significantly improved neurological function. [7][8][9][10][11] Unfortunately, results in humans have been less sanguine.…”

Travmati̇k Spi̇nal-Kord Lezyonlu Hastalarda Kollajen İle İndüklenen Trombosi̇t Agregasyonu

“…Spinal travma, mekanik hasarın yanısıra, sekonder patolojik değişiklikler olarak tanımlanan bir seri biyokimyasal, metabolik ve inflamatuvar süreçlere yol açar (8,9). Bu süreçlerde; poliansatüre yağ asitleri, prostanoidler, lökotrienler ve serbest radikaller gibi çe-şitli ürünlerin rol oynayabileceği öne sürülmektedir (10).…”