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Early perifocal cell changes and edema in traumatic injury of the spinal cord are reduced by indomethacin, an inhibitor of prostaglandin synthesis

Experimental study in the rat

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Summary

The possibility that prostaglandins participate in the formation of perifocal edema and cell changes following a localized trauma to the spinal cord was investigated in a rat model. A laminectomy was performed in urethane-anesthetized animals at the thoracic T10–11 segment. Using a scalpel blade a unilateral lesion, about 2 mm deep and 5 mm long was made 1 mm to the right of the midline. The deepest part of the injury occupied Rexed's lamina VII of the dorsal horn. Animals were pretreated with the prostaglandin synthesis inhibitor, indomethacin (10 mg/kg, i.p. 30 min prior to trauma). Five hours after the injury the water content was determined and cell changes in and around the primary lesion were examined by light and electron microscopy. Normal and injured rats without indomethacin pretreatment served as controls. Untreated injured rats showed a profound increase of water content in the traumatized T10–11, the rostral (T9) and caudal (T12) segments compared with normal rats. These segments also exhibited marked cell changes in ipsilateral and contralateral dorsal and ventral horns. The gray matter had a spongy appearance and some nerve cells were condensed and distorted. The white matter contained many distorted fibers. Immunostaining for myelin basic protein showed a marked reduction of reaction product in the injured animals compared with normal rats. Ultrastructurally widened extracellular spaces, cytoplasmic vacuolation, swollen and condensed neurons, swollen astrocytes and vesiculation of myelin were frequent findings. Pretreatment of rats with indomethacin significantly reduced the accumulation of water in the traumatized and in the rostral and caudal segments. The structural changes were less pronounced particularly in the cranial and caudal segments. The results indicate that prostaglandins somehow are involved in the pathophysiology of perifocal spinal cord injury and influence both the fluid microenvironment and the early cell changes.

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Supported by grants from the Swedish Medical Research Council projects nr 320, Trygg-Hansa, Söderbergs stiftelse, Hedlunds stifelse, Swärds stiftelse Thurings stiftelse, RTP, Wallenius Line, Ahléns and from the University Grants Commission New Delhi, India

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Sharma, H.S., Olsson, Y. & Cervós-Navarro, J. Early perifocal cell changes and edema in traumatic injury of the spinal cord are reduced by indomethacin, an inhibitor of prostaglandin synthesis. Acta Neuropathol 85, 145–153 (1993). https://doi.org/10.1007/BF00227761

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