Abstract
The effects of reversible middle cerebral artery occlusion on regional pH and ATP distribution were studied in a new stroke model in rats by a planimetric method. Thirty minutes of ischemia was followed by 2, 4 and 24 hours of reperfusion. Ischemia resulted in acidosis and ATP depletion. In some areas tissue pH reached the threshold of the umbelliferone method (about pH 6.0). Areas with ATP depletion were significantly smaller than regions of pH alteration not only at the end of ischemia but during the first 4 hours of recirculation as well. By 4 hours of reperfusion large areas with altered pH were associated with ATP depletion in smaller regions, mostly in the hippocampus and the frontal cortex. The areas of ATP depletion were acidic initially, but by 4 hours alkaline pH could also be detected. Twenty four hours after ischemia alkaline areas (pH>7.4) were found with ATP depletion, suggesting irreversible tissue damage, in cortical areas, in the hippocampus, and in the thalamus. By 24 hours of reperfusion there was no significant difference between the size of areas with altered pH and ATP depletion.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Astrup J, Siesjö BK, Symon L (1981) Thresholds in cerebral ischemia. The ischemic penumbra.Stroke 12:723–725
Bereczki D, Csiba L, Németh Gy (1988) The vulnerability of gerbils to focal cerebral ischemia. Neurological signs and regional biochemical changes after ischemia and recirculation.Ear Arch Psychiatry Neurol Sci 238:11–18
Crumrine RC, LaManna JC (1991) Regional cerebral metabolites, blood flow, plasma volume and mean transit time in total cerebral ischemia in the rat.J Cereb Blood Flow Metab 11:272–282
Csiba L, Paschen W, Hossmann KA (1983) A topographic quantitative method for measuring brain tissue pH under physiological and pathophysiological conditions.Brain Res 289:334–337
Csiba L, Bereczki D, Paschen W, Linn F (1988) The correlation between electrophysiological parameters (EEG, DC and tissue available O2) and regional metabolites (pH, ATP, glucose, NADH, K) after 45 min MCA occlusion and 3 hours recirculation in cats. In: Mechanisms of cerebral hypoxia and stroke. Ed. Somjen G, Plenum Press, New York, pp 137–138
Csiba L, Bereczki D, Shima T, Okada Y, Yamane K, Yamada T, Nishida M, Okita S (1992) A modified model of reversible middle cerebral artery embolization in rats without craniectomy.Acta Neurochir (Wien)114:51–58
Folbergrová J, Memezawa H, Smith M-L, Siesjö BK (1992) Focal and perifocal changes in tissue energy state during middle cerebral artery occlusion in normo- and hyperglycemic rats.J Cereb Blood Flow Metab 12:25–33
Garcia JH, Anderson ML (1989) Physiopathology of cerebral ischemia.Crit Rev Neurobiol 4:303–324
Gibson G, Miller SA, Venables GS, Strong J (1983) Evidence of acidosis in the ischemic penumbra.J Cereb Blood Flow Metab 3: (Suppl 1) S401
Graf R, Kataoka K, Rosner G, Heiss WD (1986) Cortical deafferentation in cat focal ischemia: disturbance and recovery of sensory functions in cortical areas with different degrees of cerebral blood flow reduction.J Cereb Blood Flow Metab 6:566–573
Hossmann KA (1982) Treatment of experimental cerebral ischemia.J Cereb Blood Flow Metab 2:275–297
Kaplan BA, Pulsinelli WA (1989) Energy metabolites in the ischemic penumbra (Abstract).Soc Neurosci Abstr 15:855
Kim S-H, Handa H, Ishikawa M, Hirai O, Yoshida S, Imadaka K (1985) Brain tissue acidosis and changes of energy metabolism in mild incomplete ischemia. Topographical study.J Cereb Blood Flow Metab 5:432–438
Kogure K, Alonso FO (1978) A pictorial representation of endogenous brain ATP by a bioluminescent method.Brain Res 154:273–284
Kotila M (1984) Declining incidence and mortality of stroke?Stroke 15:255–259
Kumpski O, Staub F, Jansen M, Schödel F, Baethmann A (1988) Glial swelling during extracellular acidosisin vitro. Stroke19:385–392
Mauton KG, Baum HM (1984) CVD-mortality 1968–1978:observations and implications.Stroke 15:451457
Molnár L, Hegedüs K, Fekete I (1988) A new model for inducing transient cerebral ischemia and subsequent reperfuison in rabbits without craniectomy.Stroke 19:1262–1266
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 6:414–424
Nedergaard M (1987) Neuronal injury in the infarct border: a neuropathological study in the rat.Acta Neuropathol 73:267–274
Obrenovitch TP, Garofalo O, Harris RJ, Bordi M, Ono F, Momma F, Bachelard HS, Symon L (1988) Brain tissue concentrations of ATP, phosphocreatine, lactate and tissue pH in relation to reduced cerebral flow following experimental acute middle cerebral artery occlusion.J Cereb Blood Flow Metab 8:866–874
O'Brien MD, Waltz AG (1973) Transorbital approach for occluding the middle cerebral artery without craniectomy.Stroke 4:201–206
Paschen W, Niebuhr I, Hossmann K-A (1981) A bioluminescence method for the demonstration of regional glucose distribution in brain slices.J Neurochem 36:513–517
Paxinos G, Watson C (1982) The rat brain in stereotaxic coordinates. Sydney, Academic Press.
Peek EK, Lockwood AH, Izumiyama M, Yap EWH, Labove J (1989) Glucose metabolism and acidosis in the metabolic penumbra of rat brain.Metab Brain Dis 4:261–272
Pontén U, Ratcheson RA, Salfford LG, Siesjö BK (1973) Optimal freezing conditions for cerebral metabolites inrats. J Neurochem21:1127–1138
Raynaud C., Rancurel G, Samson Y, Baron JC, Soucy JP, Kieffer E, Cabanis E, Majdalani A, Ricard S, Bardy A, Bourguignon M, Syrota A, LassenN (1987) Pathophysiologic study of chronic infarcts with I-123 isopropyl iodo-amphetamine (IMP): the importance of periinfarct area.Stroke 18:21–29
Rodziewicz GS, Selman WR, Ricci A, Lust WD, Ratcheson RA (1987) Metabolic penumbra: a small volume (Abstract)Stroke 18:288
Selman WR, Ricci AJ, Cumrine RC, LaManna JC, Ratcheson RA, Lust WD (1990) The evolution of focal ischemic damage: a metabolic analysis.Metab Brain Dis 15:33–44
Strong AJ, Kirby M, Monteiro E (1991) Calibration of the umbelliferone fluorescence method for measurement of brain pH in coronal sections.J Cereb Blood Flow Metab 11(Suppl 2):S466
Tamura A, Graham DJ, McCulloch J, Teasdale GM (1981) Focal cerebral ischemia in the rat: 1. Description of technique and early neuropathological consequence following MCA occlusion.J Cereb Blood Flow Metab 1:53–60
Welsh FA (1984) Regional evaluation of ischemic metabolic alterations.J Cereb Blood Flow Metab 4:309–316
Welsh FA, Marcy VR, Sims RE (1991) NADH fluorescence and regional energy metabolites during focal ischemia and reperfusion of rat brain.J Cereb Blood Flow Metab 11:459–465
Yamane K, Shima T, Okada Y, Takeda T, Uozumi T (1990) Pathophysiological studies in the rat cerebral embolization model: measurement of epidural pressure and evaluation of tissue pH and ATP. ActaNeurochir (Suppl)51:223–225
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bereczki, D., Csiba, L. Spatial and temporal changes in tissue pH and ATP distribution in a new model of reversible focal forebrain ischemia in the rat. Metab Brain Dis 8, 125–135 (1993). https://doi.org/10.1007/BF00996926
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00996926