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.
Similar content being viewed by others
References
Abe K, Yoshidomi M, Kogure K (1989) Arachidonic acid metabolism in ischemic neuronal damage. Ann NY Acad Sci 559:259–268
Anderson DK, Sauders RD, Demediuk P, Dugan LL, Braughler JM, Hall ED, Means ED, Horrocks LA (1985) Lipid hydrolysis and peroxidation in injured spinal cord: partial protection with methylprednisolone or vitamin E and selenium. CNS Trauma 2:257–267
Balentine JD (1988) Spinal cord trauma: in search of the meaning of granular axoplasm and vesicular myelin. J Neuropathol Exp Neurol 47:77–92
Banik NL, Powers JM, Hogan EL (1980) The effects of spinal cord trauma on myelin. J Neuropathol Exp Neurol 39:232–244
Barkai AI, Bazan NG (1989) Arachidonic acid metabolism in the nervous system. Physiological and pathological significance. Ann NY Acad Sci 559, New York
Bhattacharya SK, Dasgupta G, Sen AP (1989) Prostaglandins modulate central serotonergic neurotransmission. Indian J Exp Biol 27:393–398
Braughler JM, Duncan LA, Chase RL (1985) Interaction of lipid peroxidation and calcium in the pathogenesis of neuronal injury. CNS Trauma 2:269–283
Chan PH, Fishman RA, Caronna J, Schmidley JW, Prioleau G, Lee J (1983) Induction of brain edema following intracerebral injection of arachidonic acid. Ann Neurol 13:625–632
Chan PH, Longar S, Chen S, Yu ACH, Hillard L, Chu L, Imaizumi S, Pereira B, Moore K, Woolworth V, Fishman R (1989) The role of arachidonic acid and oxygen radical metabolites in the pathogenesis of vasogenic brain edema and astrocytic swelling. Ann NY Acad Sci 559:237–247
de la Torre JC (1981) Spinal cord injury. Review of basic and applied research. Spine 6:315–335
Demediuk P, Faden AI (1989) Eicosanoid production after traumatic spinal cord injury in the rat. Inhibition by BW 755c and potentiation by hypomagnesia. Am NY Acad Sci 559:433–434
Demediuk P, Saunders RD, Clendenon NR, Means ED, Anderson DK, Horrocks LA (1985) Changes in lipid metabolism in traumatized spinal cord. Prog Brain Res 63:211–226
Demediuk P, Faden AI, Vink R, Romhanyi R, McIntosh TK (1989) Effects of traumatic brain injury on arachidonic acid metabolism and brain water content in the rat. Ann NY Acad Sci 559:431–432
Dey PK, Sharma HS (1983) Ambient temperature and development of brain edema in anaesthetized animals. Indian J Med Res 77:554–563
Dey PK, Sharma HS (1984) Influence of ambient temperature and drug treatments on brain edema induced by impact injury on skull in rat. Indian J Physiol Pharmacol 28:177–186
Dey PK, Feldberg W, Gupta KP, Milton AS, Wendlandt S (1974) Further studies on the role of prostaglandin in fever. J Physiol (Lond) 241:629–646
Dey PK, Feldberg W, Wendlandt S (1974) Lipid A and prostaglandins. J Physiol (Lond) 239:102–103
Elliott KAC, Jasper H (1949) Measurement of experimentally induced brain swelling and shrinkage. Am J Physiol 157:122–129
Faden AI, Salzman S (1992) Pharmacological strategies in CNS trauma, Trends Pharmacol Sci 13:29–35
Faden AI, Lemke M, Demediuk P (1988) Effects of BW755C, a mixed cyclo-oxygenase-lipoxygenase inhibitor, following traumatic spinal cord injury in rats. Brain Res 463:63–68
Furlow TW, Hallenbeck JM (1978) Indomethacin prevents in impaired perfusion in the dog's brain after global ischemia. Stroke 9:591–594
Gustafsson LE (1989) Mechanisms involved in the action of prostaglandins as modulators of neurotransmission. Ann NY Acad Sci 559:178–181
Hall ED, Wolf DF (1988) A pharmacological analysis of the pathophysiological mechanisms of post-traumatic spinal cord ischemia. J Neurosurg 64:951–961
Hallenbeck JM, Jacobs TP, Faden AI (1983) Combined PGI2, indomethacin, and heparin improves neurological recovery after spinal trauma in cats. J Neurosurg 58:749–754
Hertting G, Seregi A (1989) Formation and function of eicosanoids in the central nervous system. Ann NY Acad Sci 559:84–99
Hsu CY, Halushka PV, Hogan EL, Banik NL, Lee WA, Perot PL (1985) Alteration of thromboxane and prostacyclin levels in experimental spinal cord injury. Neurology 35:1003–1009
Hsu CY, Halushka PV, Hogan EL, Cox RD (1986) Increased thromboxane level in experimental spinal cord injury. J Neurol Sci 74:289–296
Hsu CY, Halushka PV, Spicer KM, Hogan EL, Martin HF (1988) Temporal profile of thromboxane-prostacyclin imbalance in experimental spinal cord injury. J Neurol Sci 83:55–62
Hsu CY, Liu TH, Xu J, Hogan EL, Chao J, Sun G, Tai HH, Beckman JS, Freeman BA (1989) Arachidonic acid and its metabolites in cerebral ischemia. Ann NY Acad Sci 559:282–295
Iannotti F, Crockard A, Ladds G, Symon L (1981) Are prostaglandins involved in experimental ischemic edema in gerbils? Stroke 12:301–306
Kim HJ, Levasseur JE, Patterson JL, Jackson GF, Madge GE, Povlishock JT, Kontos HA (1989) Effect of indomethacin on acute mortality in experimental brain injury. J Neurosurg 71:565–572
Kiwak KJ, Moskowitz MA, Levine L (1985) Leukotrienes production in gerbil brain after ischemic insult, subaracnoid hemorrhage, and concussive injury. J Neurosurg 62:865–869
Lands WEM, Samuelsson B (1968) Phospholipid precursors of prostaglandins. Biochim Biophys Acta 164:426–429
Means ED, Anderson DK (1987) The pathophysiology of acute spinal cord injury. In: Davidoff RA (ed) Handbook of the Spinal Cord, vol 5. Marcel Dekker, New York, pp 19–61
Monacada S, Vane JP (1979) Pharmacology and endogenous role of prostaglandin. Pharmacol Rev 30:293–331
Ojeda SR, Urbanski HF, Junier M-P, Capdevilla J (1989) The role of arachidonic acid and its metabolites in the release of neuropeptides. Ann NY Acad Sci 559:187–191
Olsson Y, Sharma HS, Pettersson CÅV (1990) Effects of p-chlorophenylalanine on microvascular permeability changes in spinal cord trauma. An experimental study in the rat using 131I-sodium and lanthanum tracers. Acta Neuropathol 79:595–603
Olsson Y, Sharma HS, Pettersson CÅV, Cervós-Navarro J (1992) Endogenous release of neurochemicals may increase vascular permeability, induce edema and influence on cell changes in trauma to the spinal cord. Prog Brain Res. 91:197–203
Pappius HM, Wolfe LS (1983) Effects of indomethacin and ibuprofen on cerebral metabolism and blood flow in traumatized brain. J Cereb Blood Flow Metab 3:448–459
Salzman SK, Puniak MA, Liu Z-J, Maitland-Heriot RP, Freeman GM, Agresta CA (1991) The serotonin antagonist mianserin improves functional recovery following experimental spinal trauma. Ann Neurol 30:533–541
Samuelsson B, Goldyne M, Granström E, Hamberg M, Hammarström S, Malmsten C (1978) Prostaglandins and thromboxanes. Annu Rev Biochem 47:997–1029
Samuelsson B, Hammarström S, Borgeat P (1979) Pathway of arachidonic acid metabolism. Adv Inflam Res 1:405–411
Sharma HS, Olsson Y (1990) Edema formation and cellular alterations following spinal cord injury in the rat and their modification with p-chlorophenylalanine. Acta Neuropathol 79:604–610
Sharma HS, Olsson Y, Dey PK (1990) Early accumulation of serotonin in rat spinal cord subjected to traumatic injury. Relation to edema and blood flow changes. Neuroscience 36:725–730
Sharma HS, Cervós-Navarro J, Dey PK (1991) Rearing at high ambient temperature during later phase of the brain development enhances functional plasticity of the CNS and induces tolerance to heat stress: an experimental study in the conscious normotensive young rats. Brain Dysfunct 4:104–124
Shohami E, Shapira Y, Sidi A, Cotev S (1987) Head injury induces increased prostaglandin synthesis in rat brain. J Cereb Blood Flow Metab 7:58–63
Shohami E, Shapira Y, Cotev S (1988) Experimental closed head injury in rats: prostaglandin production in a noninjured zone. Neurosurgery 22:859–863
Shapira Y, Davidson E, Weidenfeld Y, Cotev S, Shohami E (1988) Dexamethasone and indomethacin do not affect brain edema following head injury in rats. J Cereb Blood Flow Metab 8:395–402
Siegal T, Siegal T, Shohami E, Lossos F (1990) Experimental neoplastic spinal cord compression: effect of ketamine and MK-801 on edema and prostaglandins. Neurosurgery 26:963–970
Smith WL (1986) Prostaglandin biosynthesis and its compartmentation in vascular smooth muscle and endothelial cells. Annu Rev Physiol 48:251–262
Tator CH, Fehlings MG (1991) Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms. J Neurosurg 75:15–26
Ting P (1990) Indomethacin attenuates early postischemic vasogenic edema and cerbral injury. Adv Neurol 52:119–126
Tsubokura S, Watanabe Y, Ehara H, Imamura K, Sugimoto O, Kagamiyama H, Yamamoto S, Hayaishi O (1991) Localization of prostaglandin endoperoxidase syntethase in neurons and glia in monkey brain. Brain Res 543:15–24
White RP, Hagan AA (1982) Cerebrovascular actions of prostaglandins. Pharmacol Ther 18:313–331
Wieloch T (1990) Neuronal injury and cerebrovascular disorders. Curr Opin Neurol Neurosurg 3:944–950
Winkler T, Sharma HS, Stålberg E, Olsson Y (1992) Indomethacin, an inhibitor of prostaglandin synthesis attenuates alteration in spinal cord evoked potentials and edema formation after trauma to the spinal cord of the rat. Neuroscience (in press)
Wolfe LS (1982) Eicosanoids: prostaglandins, thromboxane, leukotrienes, and other derivatives of carbon-20 unsaturated fatty acids. J Neurochem 38:1–14
Wolfe LS, Coceani F (1979) The role of prostaglandins in the central nervous system. Annu Rev Physiol 41:669–684
Wolfe LS, Pellerin L (1989) Arachidonic acid metabolites in the rat and human brain. New findings on the metabolism of prostaglandin D2 and lipoxygenase products. Ann NY Acad Sci 559:74–83
Author information
Authors and Affiliations
Additional information
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
Rights and permissions
About this article
Cite this article
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
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00227761