Abstract
Neurotrauma activates the release of membrane phospholipid-derived second messengers, such as free arachidonic acid (20:4n-6, AA) and diacylglycerols (DAGs). In the present study, we analyze the effect of cortical impact injury of low-grade severity applied to the rat frontal right sensory-motor cortex (FRC) on the accumulation of free fatty acids (FFAs) and DAGs in eight brain areas 30 min and 24 hours after the insult. At these times, accumulation of FFAs and DAGs occurred mainly in the damaged FRC. The cerebellum was the only other brain area that displayed a significant accumulation of DAGs by day one post-injury. By 30 min, accumulation of free AA in the FRC displayed the greatest relative increase (300% over sham value), followed by free docosahexaenoic acid (22:6n-3, DHA, 150%), while both 20:4-DAGs and 22:6-DAGs were increased 100% over sham values. At day one, free 22:6 and 22:6-DAGs showed the greatest increase (590% and 230%, respectively). These results suggest that TBI elicits the hydrolysis of phospholipids enriched in excitable membranes, targeting early on 20:4-phospholipids (by 30 min post-trauma) and followed 24 hours later by preferential hydrolysis of DHA-phospholipids. These lipid metabolic changes may contribute to the initiation and maturation of neuronal and fiber track degeneration observed following cortical impact injury.
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REFERENCES
Faden, A. I. and Vink R. 1989. Chemical pathology of CNS trauma. Pages 14–21, in D. Bihari and J. W. Holaday (eds), Update in Intensive Care and Emergency Medicine, Vol. 9: Brain Failure. Springer: Berlin.
Katayama, Y., Becker, D. P., Tamura, T., and Hovda, D. A. 1990. Massive increase in extracellular potassium and the indiscriminate release of glutamate following concussive brain injury. J. Neurosurg. 73:889–900.
Hayes, R. L., Jenkins, L. W., and Lyeth, B. G. 1991. Neurotransmitter mediated mechanisms of traumatic brain injury: acetylcholine and exitatory amino acids. Pages 9–25, in J. A. Jane, D. K. Anderson, J. C. Torner, and W. Young (eds), Central Nervous System Trauma Status Report. Mary Ann Liebert Inc., New York.
Nilsson, P., Hillered, L., Ponten, U., and Ungerestdet, U. 1990. Changes in cortical extracellular levels of energy-related metabolites and amino acids following concussive brain injury in rats. J. Cereb. Blood Flow Metab. 10:631–637.
Nilsson, P., Hillered, L., Olsson, Y., Sheardown, M. J., and Hansen, A. J. 1993. Regional changes in interstitial K+ and Ca2+ levels following cortical compression contusion trauma in rats. J. Cereb. Blood Flow Metab. 13:183–192.
Siesjö, B. K. 1993. Basic mechanisms of traumatic brain damage. Neurotrauma. 22:959–969.
Choi, D. W. 1988. Glutamate neurotoxicity and diseases of the nervous system. Neurochem. 1:623–634.
Nilsson, P., Laursen, H., Hillered, L., and Hansen, A. J. 1996. Calcium movements in traumatic brain injury: The role of glutamate receptor-operated ion channels. J. Cereb. Blood Flow Metab. 16:262–270.
Nicotera, P., Bellomo, G., and Orrenius, S. 1992. Calcium-mediated mechanisms in chemically induced cell death. Annu. Rev. Pharmacol. Toxicol. 32:449–470
Tymianski, M. and Tator C. H. 1996. Normal and abnormal calcium homeostasis in neurons: A basis for the pathophysiology of traumatic and ischemic central nervous system injury. Neurosurgery. 38:1176–1195.
Bonventre, J. V. 1996. Roles of phospholipases A2 in brain cell and tissue injury associated with ischemia and excitotoxicity. J. Lipid Mediat. Cell Signal. 14:15–23.
Farooqui, A. A., Yang, H.-C., and Horrocks, L. 1997. Involvement of phospholipase A2 in neurodegeneration. Neurochem. Int. 30:517–522.
Bazan, N. G. and Rodriguez De Turco, E. B. 1980. Membrane lipids in the pathogenesis of brain edema: Phospholipids and arachidonic acid, the earliest membrane components changed at the onset of ischemia. Pages 197–205, in J. Cervos-Navarro and R. Ferszt (eds), Advances in Neurology: Brain Edema. New York, Raven Press.
Bazan, N. G., Rodriguez De Turco, E. B., and Allan, G. 1995. Mediators of injury in neurotrauma: Intracellular signal transduction and gene expression. J. Neurotrauma. 12:789–911.
Shohami, E., Shapira, Y., Yadid, G., Reisfeld, N., and Yedgar, S. 1989. Brain phospholipase A2 is activated after experimental closed head injury in the rat. J. Neurochem. 53:1541–1546.
Wei, E. P., Lamb, R. G., and Kontos, H. A. 1982. Increased phospholipase C activity after experimental brain injury. J. Neurosurg. 56:695–698.
Dhillon, H. S., Donaldson, D., Dempsey, R. J., and Prasad, M. R. 1994. Regional levels of free fatty acids and Evans blue extravasation after experimental brain injury. J. Neurotrauma. 11:405–415.
Dhillon, H. S., Carbary, T., Dose, J., Dempsey R. J., and Prasad, M. R. 1995. Activation of phosphatidylinositol bisphosphate signal transduction pathway after experimental brain injury: a lipid study. Brain Res. 698:100–106.
Dhillon, H. S., Carman, H. M., Zhang, D., Scheff, S. W., and Renuka Prasad, M. 1999. Severity of Experimental brain injury on lactate and free fatty acid accumulation and Evans blue extravasation in the rat cortex and hippocampus. J. Neurotrauma 16:455–469.
Soblosky, J. S., Matthews, M. A., Davidson, J. F., Tabor, S. L., and Carey, M. E. 1996a. Traumatic brain injury of the forelimb and hindlimb sensorimotor areas in the rat: physiological, histological and behavioral correlates. Behav. Brain Res. 79:79–92.
Soblosky, J. S., Tabor, S. L., Matthews, M. A., Davidson, J. F., Chorney, D. A., and Carey, M. E. 1996b. Reference memory and allocentric spatial localization deficits after unilateral cortical brain injury in the rat. Behav. Brain Res. 80:185–194.
Matthews, M. A., Carey, M. E., Soblosky, J. E., Davidson, J. F., and Tabor, S. L. 1998. Focal brain injury and its effects on cerebral mantle, neurons, and fiber tracks. Brain Research 794:1–18.
Homayoun, P., Rodriguez De Turco, E. B., Parkins, N. E., Lane, D. C., Soblosky, J., Carey, M. E., and Bazan, N. G. 1997. Delayed phospholipid degradation in rat brain after traumatic brain injury. J. Neurochem. 69:199–205.
Bazan, N. G. 1970. Effects of ischemia and electroconvulsive shock on free fatty acid pool in the brain. Biochim. Biophys. Acta 218:1–10.
Aveldaño, M. I. and Bazan, N. G. 1975a. Rapid production of diacylglycerols enriched in 20:4 and stearate during early brain ischemia. J. Neurochem. 25:919–920.
Aveldaño, M. I. and Bazan, N. G. 1975b. Differential lipid deacylation during brain ischemia in a homeotherm and poikilotherm. Content and composition of free fatty acids and triacylglycerols. Brain Res. 100:99–110.
Katsura, K., Rodriguez De Turco, E. B., Folbergrova, J., Bazan, N. G., and Siesjö, B. K. 1993. Coupling among energy failure, loss of ion homeostasis, and phospholipase A2 and C activation during ischemia. J. Neurochem. 61:1677–1684.
Rodriguez De Turco, E. B., Morelli De Liberti, S. A., and Bazan, N. G. 1983. Stimulation of free fatty acid and diacylglycerol production in cerebrum and cerebellum during bicuculline-induced status epilepticus. Effect of pretreatment with alpha-methyl-p-tyrosine and p-chlorophenylalanine. J. Neurochem. 40:252–259.
Reddy, T. S. and Bazan, N. G. 1987. Arachidonic acid, stearic acid and diacylglycerol accumulation correlates with the loss of phosphatidylinositol 4,5-bisphosphate in cerebrum 2 seconds after electroconvulsive shock. Complete reversion of changes 5 minutes after stimulation. J. Neurosci. Res. 18:449–455.
Birkle, D. L. and Bazan, N. G. 1987. Effect of bicuculline-induced status epilepticus on prostaglandins and hydroxyeicosatetraenoic acids in rat brain subcellular fractions. J. Neurochem. 48:1768–1778.
Visioli, F., Rhin, L. L., Rodriguez De Turco, E. B., Kreisman, N. R., and Bazan, N. G. 1993. Free fatty acid and diacylglycerol accumulation in the rat brain during recurrent seizures is related to cortical oxygenation. J. Neurochem. 61:1835–1842.
Marcheselli, V. L. and Bazan, N. G. 1990. Quantitative analysis of fatty acids in phospholipids, diacylglycerol, free fatty acids, and other lipids. J. Nutr. Biochem. 1:382–388.
Nakano, S., Kogure, K., Abe, K., and Yae, T. 1990. Ischemia-induced alterations in lipid metabolism of the girbil cerebral cortex: I. Changes in free fatty acid liberation. J Neurochem 54: 1911–1916.
Goto, Y., Okamoto, S., Yonekawa, Y., Taki, W., Kikuchi, H., Handa, H., and Kito, M. 1988. Degradation of phospholipid molecular species during experimental cerebral ischemia in the rat. Stroke 19:728–735.
Politi, L. E., Rodriguez De Turco, E. B., and Bazan, N. G. 1985. Dexamethasone effects on free fatty acid and diacylglycerol accumulation during experimentally induced vasogenic brain edema. Neurochem. Pathol. 3:249–269.
Cotman, C., Blank, M. L., and Moehl, A. 1969. Lipid composition of synaptic plasma membrane isolated from brain by zonal centrifugation. Biochem. 3:4606–4611.
Sun, G. Y. and Sun, A. Y. 1972. Phospholipids and acyl groups of synaptosomal and myelin membranes isolated from the cerebral cortex of squirrel monkey (Saimiri Sciureus). Biochim. Biophys. Acta. 280:306–315.
Homayoun, P., Durand, G., Pascal, G., and Bourre, J. M. 1988. Alteration in fatty acid composition of adult rat brain capillaries and choroid plexus induced by diet deficient in n-3 fatty acids: slow recovery after substitution with a nondeficient diet. J. Neurochem. 51:45–48.
Bénistant, C., Dehouck, M.-P., Fruchart, J.-C., Cecchelli, R., and Lagarde, M. 1995. Fatty acid composition of brain capillary endothelial cells: Effect of coculture with astrocytes. J. Lipid Res. 36:2311–2319.
Lecompte, M., Paget, C., Ruggiero, D., Wiernsperger, N., and Lagarde, M. 1996. Docosahexaenoic acid is a major n-3 polyunsaturated fatty acid in bovine retinal microvessels. J. Neurochem. 66:2160–2167.
Salem, N. and Niebylski, C. D. 1995. The nervous system has an absolute molecular species requirement for proper function. Mol. Membrane Biol. 12:131–134.
Bazan, N. G. 1990. Involvement of arachidonic acid and platelet-activating factor in the response of the nervous system to ischemia and convulsions. Pages 277–289, in N. G. Bazan (ed), Lipid Mediators in Ischemic Brain Damage and Experimental Epilepsy. New Trends in Lipid Mediators. Karger, Basel.
Bazan, N. G., Allan, G., and Rodriguez De Turco, E. B. 1993. Role of phospholipase A2 and membrane-derived lipid second messengers in excitable membrane function and transcriptional activation of genes: Implication in cerebral ischemia and neuronal excitability. Prog. Brain Res. 96:247–257.
Bazan, N. G. 1971. Phospholipase A1 and A2 in brain subcellular fractions. Acta. Physiol. Latino Am. 21:101–106.
Farooqui, A. A., Hirashima, Y., and Horrocks, L. A. 1992. Brain phospholipases and their role in signal transduction. Adv. Exp. Med. Biol. 318:11–25.
Woelk, H. and Porcellati, G. 1973. Subcellular distribution and kinetic properties of rat brain phospholipases A1 and A2. Hoppe-Seyler's Z. Physiol. Chem. 354:90–100.
Klein, J., Chalifa, V., Liscovitch, M., and Löffelholz, K. 1995. Role of phospholipase D activation in nervous system physiology and pathophysiology. J. Neurochem. 65:1445–1455.
Kolko, M., Decoster, M. A., Rodriguez De Turco, E. B., and Bazan, N. G. 1996. Synergy by secretory phospholipase A2 and glutamate on inducing cell death and sustained arachidonic acid metabolic changes in primary cortical neuronal cultures. J. Biol. Chem. 271:32722–32728.
Owada, Y., Tominaga, T., Yoshimoto, T., and Kondo, H. 1994. Molecular cloning of rat DNA for cytosolic phospholipase A2 and the increased gene expression in the dentate gyrus following transient forebrain ischemia. Mol. Brain Res. 25:364–368.
Lauritzen, I., Heurteaux, C., and Lazdanski, M. 1994. Expression of group II phospholipase A2 in rat brain after severe forebrain ischemia nad in endotoxic shock. Brain Res. 651:353–356.
Bonventre J. V., Huang, Z., Taheri, M. R., O'Leary, E., Li, E., Moskowitz, M. A., and Sapirstein, A. 1997. Reduced fertility and postischemic brain injury in mice deficient in cytosolic phospholipase A2. Nature 390:622–625.
Pete, M. J., Ross, A. H., and Exton, J. H. 1994. Purification and properties of phospholipase Al from bovine brain. J. Biol. Chem. 269:19494–19500.
Pete, M. J. and Exton, J. H. 1996. Purification of a lipophospholipase from bovine brain that selectively deacylates arachidonoyl-substituted lipophosphatidycholine. J. Biol. Chem. 271:18114–18121.
Pete, M. J., Wu, D. W., and Exton, J. H. 1996. Subcellular fractions of bovine brain degrade phosphatidycholine by sequential deacylation of the sn-1 and sn-2 positions. Biochim. et Biophys. Acta 1299:325–332.
Exton, J. H. 1994. Phosohatidycholine breakdown and signal transduction. Biochim. Et Biophys. Acta 1212:26–42.
Reddy, T. S., Sprecher, H., and Bazan, N. G. 1984. Long-chain acyl-coenzyme A synthetase from rat brain microsomes. Kinetics studies using [1-14C]docosashexaenoic acid substrate. Eur J Biochem. 145:21–29.
Reddy, T. S. and Bazan, N. G. 1985. Synthesis of arachidonoyl coenzyme A and docosahexaenoyl coenzyme A in synaptic plasma membranes of cerebrum and microsomes of cerebrum, cerebellum, and brain stem of rat brain. J Neurosci Res 13: 381–390.
Rabin, O., Chang, M. C. J., Grange, E., Bell, J., Rapoport, S. I., Deutsch, J., and Purdon, A. D. 1998. Selective acceleration of arachidonic acid reincorporation into brain membrane phospholipid following transient ischemia in awake gerbil. J. Neurochem. 70:325–334.
Rabin, O., Deutsch, J., Grange, E., Pettigrew, K. D., Chang, M. C. J., Rapoport, S. I., and Purdon, A. D. 1997. Changes in cerebral acyl-CoA concentrations following ischemia-reperfusion in awake gerbils. J. Neurochem. 68:2111–2118.
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Homayoun, P., Parkins, N.E., Soblosky, J. et al. Cortical Impact Injury in Rats Promotes a Rapid and Sustained Increase in Polyunsaturated Free Fatty Acids and Diacylglycerols. Neurochem Res 25, 269–276 (2000). https://doi.org/10.1023/A:1007583806138
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DOI: https://doi.org/10.1023/A:1007583806138