Summary
In order to investigate the time course change of local cerebral blood flow (1CBF) and local cerebral glucose metabolism (1CGM) and the effect of MK-801 (dizocilpine), an NMDA receptor antagonist on glucose metabolism in a middle cerebral artery occlusion-reperfusion model,14C-Iodo-antipyrine and14C-Deoxyglucose autoradiographic method have been used. The 1CBF was reduced to 0–10% of the control level in the ischaemic core and to 12–40% in the ischaemic penumbra between 60 and 120 min after the onset of the ischaemia. In the ischaemic core, the marked hyperfusion appeared at 15 min and maintained about 30 to 45 min following reperfusion. In the ischaemic penumbra, the hyperfusion during reperfusion was not found. Hypermetabolism occurred at 30 min and reached to the peak at 60 min after the middle cerebral artery (MCA) occlusion both in the ischaemic core and in the penumbra. The shift from hyper- to hypometabolism was observed during the ischaemia. The reperfusion following 2 hours of MCA occlusion facilitated the decrease of cerebral glucose metabolism in the ischaemic region. The pretreatment of MK-801 (0.4 mg/kg) inhibited both increased glucose metabolism during the ischaemia and decreased glucose metabolism during the reperfusion. The effect of limiting decreased glucose metabolism during the reperfusion by MK-801 was remarkable in the ischaemic penumbra. These findings support the hypothesis that excitation-induced hypermetabolism play a major role in the ischaemic insult following focal cerebral vascular occlusion.
Similar content being viewed by others
References
Andine P, Jacobson I, Hagberg H (1988) Calcium uptake evoked by electrical stimulation is enhanced postischaemically and precedes delayed neuronal death in CA1 of rat hippocampus: involvement of N-methyl-D-aspartate receptors. J Cereb Blood Flow Metab 8: 799–807
Back T, Ginsberg MD, Dietrich WD, Watson BD (1996) Induction of spreading depression in the ischemic hemisphere following experimental middle cerebral artery occlusion: effect on infarct morphology. J Cereb Blood Flow Metab 16: 202–213
Back T, Hoehn-Berlage M, Kohno K, Hossmann K-A (1994) Diffusion NMR imaging in experimental stroke: correlation with cerebral metabolites. Stroke 25: 494–500
Back T, Zhao W, Ginsberg MD (1995) Three-dimensional image analysis of brain glucose metabolism-blood flow uncoupling and its electrophysiological correlates in the acute ischemic penumbra following middle cerebral artery occlusion. J Cereb Blood Flow Metab 15: 566–577
Benveniste H, Drejer J, Schousboe A, Diemer NH (1984) Elevation of the extracellular concentration of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. J Neurochem 43: 1369–1374
Bolander HG, Persson L, Hillered E, d'Argy R, Poten U, Olsson Y (1989) Regional cerebral blood flow and histopathologic changes after middle cerebral artery occlusion in rats. Stroke 20: 930–937
Chi OZ, Anwar M, Sinha AK, Weiss HR (1991) Effects of MK-801 on cerebral regional oxygen consumption in focal cerebral ischemia in rats. Circ Res 69: 414–420
Dawson VE, Dawson TM, Bartley DA, Uhl GR, Snyder SH (1993) Mechanisms of nitric oxide-mediated neurotoxicity in primary brain cultures. J Neurosci 13: 2651–2661
Drejer J, Benveniste H, Diemer NH, Schousboe A (1985) Cellular origin of ischemia-induced glutamate release from brain tissue in vivo and in vitro. J Neurochem 45: 145–151
Fieschi C, Sakurada O, Sokoloff E (1978) Eocal glucose utilization during resolution of embolic experimental ischemia. Adv Neurol 20: 223–229
Gill R, Andine P, Hillered E, Persson E, Hagberg H (1992) The effect of MK-801 on cortical spreading depression in the penumbral zone following focal ischemia in the rat. J Cereb Blood Flow Metab 12: 371–379
Gill R, Foster AC, Woodruff GN (1987) Systemic administration of MK-801 protects against ischaemic neuropathology in rats. Br J Pharmacol 91: 311
Ginsberg MD (1990) Local metabolic responses to cerebral ischemia. Cerebrovasc Brain Metab Rev 2: 58–93
Ginsberg MD, Graham DI, Busto R (1985) Regional glucose utilization and blood flow following graded forebrain ischemia in the rat: correlation with neuropathology. Ann Neurol 18: 470–481
Ginsberg MD, Smith DW, Wachtel MS, Gonzalez-Carvajal M, Busto R (1986) Simultaneous determination of local cerebral glucose utilization and blood flow by carbon-14 double-label autoradiography: method of procedure and validation studies in the rat. J Cereb Blood Flow Metab 6: 273–285
Graham SH, Chen J, Sharp FR, Simon RP (1993) Limiting ischemic injury by inhibition of excitatory amino acid release. J Cereb Blood Flow Metab 13: 88–97
Hagberg H, Lehmann A, Sandberg M, Nustrom B, Jacobson I, Hmberger A (1985) Ischemia-induced shift of inhibitory and excitatory amino acids from intra- to extracellular compartments. J Cereb Blood Flow Metab 5: 413–419
Hakim AM, Hogan MJ, Carpenter S (1992) Time course of cerebral blood flow and histological outcome after focal cerebral ischemia in rats. Stroke 23: 1138–1144
Hasegawa Y, Fisher M, Baron BM, Metealf G (1994) The competitive NMDA antagonist MDL-100,453 reduces infarct size after experimental stroke. Stroke 25: 1241–1246
Hossmann K-A, Mies G, Paschen W, Csiba L, Bodsch W, Rapin JR, Le Poncin-Lafitte M, Takahashi K (1985) Multiparametric imaging of blood flow and metabolism after middle cerebral artery occlusion in cats. J Cereb Blood Flow Metab 5: 97–107
Iijima T, Mies G, Hossmann KA (1992) Repeated negative DC deflections in rat cortex following middle cerebral artery occlusion are abolished by MK-801: effect on volume of ischemic injury. J Cereb Blood Flow Metab 12: 727–733
Koizumi J, Yoshida Y, Nakazawa T, Ooneda G (1986) Experimental studies of ischemic brain edema. 1. A new experimental model of cerebral embolism in rats in which recirculation can be introduced in the ischemic area. Jpn J Stroke 8: 1–8 (Jpn)
Koizumi Z, Yoshida Y, Nishigaya K, Kanai H, Ooneda G (1989) Experimental studies of ischemic brain edema. Effect of recirculation of the blood flow after ischemia on post ischemic brain edema. Jpn J Stroke 11: 11–17 (Jpn)
Lauritzen M, Hansen AJ (1992) The effect of glutamate receptor blockade on anoxic depolarization and cortical spreading depression. J Cereb Blood Flow Metab 12: 223–229
Levy DE, Duffy TE (1977) Cerebral energy metabolism during transient ischemia and recovery in the gerbil. J Neurochem 28: 63–70
MacDermott AB, Mayer ML, Westbrook GL (1986) NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurons. Nature 321: 519–522
Mies G, Auer LM, Ebhardt G, Traupe H, Heiss W-D (1983) Flow and neuronal density in tissue surrounding chronic infarction. Stroke 14: 22–27
Nakai H, Matsuda H, Takara E, Diksic M, Meyer E, Yamamoto YL (1987) Simultaneous in vivo measurement of lumped constant and rate constants in experimental cerebral ischemia using F-18 FDG. Stroke 18: 158–167
Nedergaard M, Gjedde A, Diemer NH (1986) Focal ischemia of the rat brain: autoradiographic determination of cerebral glucose utilization, glucose content, and blood flow. J Cereb Blood Flow Metab 6: 607–615
Nishigaya K, Yoshida Y, Sasuga M, Nukui H, Ooneda G (1991) Effect of recirculation on exacerbation of ischemic vascular lesions in rat brain. Stroke 22: 635–642
Nishikawa T, Kirsch JR, Kochler RC, Miyabe M, Traystman RJ (1994) Competitive N-Methyl-D-Aspartate receptor blockade reduces brain injury following transient focal ischemia in cats. Stroke 25: 2258–2263
Palkovits M, Brownstein MJ (1988) Maps and guide to microdissection of the rat brain. In: Maps. Elsevier, New York, pp 81–142
Park CK, Nehls DG, Graham DI, Teasdale GM, McCulloch J (1988) The glutamate antagonist MK-801 reduces focal ischemic brain damage in the rat. Ann Neurol 24: 543–551
Pulainwlli WA, Levy DE, Duffy TE (1982) Regional cerebral blood flow and glucose metabolism following transient forebrain ischemia. Ann Neurol 11: 499–509
Reivich M (1974) Blood flow metabolism couple in brain. In: Brain dysfunction in metabolic disorders. Raven, New York, pp 125–140
Rothman SM, Olney JW (1986) Glutamate and the pathophysiology of hypoxic-ischemic brain damage. Ann Neurol 19: 105–111
Rothman SM, Olney JW (1987) Excitotoxicity and the NMDA receptor. Trends Neurosci 10: 299–302
Sakurada O, Kennedy C, Jehle J, Brown JD, Carbin GL, Sokoloff L (1978) Measurement of local cerebral blood flow with iodo-C-14-antipyrine. Am J Physiol 234: 59–66
Saturo K, Greenberg JH, Hickey WF, Reivich M (1989) Local cerebral glucose utilization in chronic middle cerebral artery occlusion in the cat. J Cereb Blood Flow Metab 9: 535–547
Siesjö BK (1992) Pathophysiology and treatment of focal cerebral ischemia, I: Pathophysiology. J Neurosurg 77: 169–184
Siesjö BK (1992) Pathophysiology and treatment of focal cerebral ischemia, II: mechanisms of damage and treatment. J Neurosurg 77: 337–354
Shiraishi K, Sharp F, Simon R (1989) Sequential metabolic changes in rat brain following middle cerebral artery occlusion: a 2-deoxyglucose study. J Cereb Blood Flow Metab 9: 765–773
Silverstein FS, Buchanan K, Johnston MV (1986) Perinatal hypoxia-ischemia disrupts striatal high-affinity [3H] glutamate uptake into synaptosomes. J Neurochem 47: 1614–1619
Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M (1977) The14C deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 28: 897–917
Tanaka K, Greenberg JH, Gonatas NK, Reivich M (1985) Regional flow-metabolism couple following middle cerebral artery occlusion in cat. J Cereb Blood Flow Metab 5: 241–252
Uematsu D, Greenberg JH, Araki N, Reivich M (1991) Mechanism underlying protective effect of MK-801 against NMDA-induced neuronal injury in vivo. J Cereb Blood Flow Metab 11: 779–785
Welsh FA, Greenberg JH, Jones SC, Ginsberg MD, Reivich M (1980) Correlation between glucose utilization and metabolic levels during focal ischemia in cat brain. Stroke 11: 79–84
Yang GY, Betz AL (1995) Reperfusion-induced injury to the blood-brain barrier after middle cerebral artery occlusion in rats. Stroke 25: 1658–1665
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Liu, Y., Mituska, S., Hashizume, K. et al. The sequential change of local cerebral blood flow and local cerebral glucose metabolism after focal cerebral ischaemia and reperfusion in rat and the effect of MK-801 on local cerebral glucose metabolism. Acta neurochir 139, 770–779 (1997). https://doi.org/10.1007/BF01420052
Issue Date:
DOI: https://doi.org/10.1007/BF01420052