Brain Tissue Acidosis and Changes of Energy Metabolism in Mild Incomplete Ischemia—Topographical Study

Abstract

Summary: Regional changes of brain tissue pH and its correlation to energy metabolism were studied in various degrees of incomplete ischemia for 5 and 60 min in the unilateral common carotid occlusion of normally fed mongolian gerbils. The degree of ischemia was evaluated by the severity of neurological deficits following 60 min of occlusion, and animals were divided into three groups: symptomatic, borderline, and asymptomatic. Changes of NADH and ATP distribution corresponded well to the degree of ischemia. On the other hand, acidosis devel oped more clearly and extended in wider areas than the The brain is highly dependent on a continuous supply of glucose and oxygen to maintain neuronal function. Thus, the brain tissue is vulnerable to ischemia for lack of energy substrate and oxygen. Although it is evident that permanent breakdown of energy metabolism following ischemia causes irre versible brain tissue damage, energy failure during ischemia does not always result in permanent damage. Experimental studies have demonstrated a better recovery of energy metabolism (Hossmann and Kleihues, 1973; Nordstrom and Siesjo, 1978; Rehncrona et aI., 1980) following complete than in complete ischemia in spite of a similar perturbation of brain energy state. Thus, it seems clear that en ergy failure during ischemia is not a limiting factor for the functional and the structural damage during the postischemic reperfusion period. Instead, other possible factors such as formation of free radicals (Flamm et aI. , 1978), accumulation of free fatty acids (Bazan, 1970), and postischemic hypoperfu sion (Paschen et aI. , 1983) lactic acidosis following severe incomplete ischemia as an important factor of irreversible brain tissue damage (Rehncrona et aI. , 1980(Rehncrona et aI. , , 1981 Kalimo et aI. , 1981; Plum et aI. , 1983). However, development of lactic acidosis and its correlation to the changes of energy state in mild incomplete ischemia, which is not detrimental enough to cause irreversible cell damage, have not been well discussed (Ginsberg et a\. , 1983). In the present study, we have investi gated regional changes of brain tissue pH in various degrees of incomplete ischemia correlating with re gional changes of energy metabolism in normally fed mongolian gerbils following acute unilateral oc clusion of the common carotid. Regional changes of brain tissue pH were measured semiquantita tively using the umbelliferone technique (Fink and Koehler, 1970;Sundt et a\. , 1978; Welsh et aI. , 1982;Csiba et a\. , 1983). Regional changes of the redox state of brain tissue were assessed using NADH fluorescence histochemistry (Welsh and Rieder, 1978), and regional changes of ATP using the luci ferine luciferase bioluminescent method (Kogure and Alonso, 1978). MATERIALS AND METHODSForty-six mongolian gerbils of either sex, weighing 50-80 g, were used in this study. The animals were allowed REGIONAL METABOLISM AND pH IN CEREBRAL ISCHEMIA 433 FIG. 1. Ultraviolet light reflectance (UV), regional NADH fluorescence (NADH), regional ATP...

Relationships Among ATP Synthesis, K+ Gradients, and Neurotransmitter Amino Acid Levels in Isolated Rat Brain Synaptosomes

“…The most precipitous decline in [CrP]/[Cr] ratios and ATP levels are observed when limitation of mitochondrial respiration is accompanied by withdrawal of glucose, i.e., when both the mitochondrial and glycolytic ATP syntheses are compromised. It is noteworthy that a large stimulation of lactate production is one of the most consistent features of in vivo cerebral ischemia and hypoxia (see, e.g., Lowry et al, 1964;Siesjo and Nilsson, 1971;Bachelard et al, 1974;Rehncrona et al, 1981) and is consistent with the observation (Kim et al, 1985) that, in intact brain, changes of pH, most likely due to lactate accumulation, precede large decreases in ATP content.…”

Effects of Traumatic Brain Injury on Cerebral High-Energy Phosphates and pH: A31P Magnetic Resonance Spectroscopy Study

“…The 3to 8-h, post-injury value of 2.5 ± 0.5 (a 48% reduc tion) reflects a post-traumatic abnormality of cere bral energy metabolism which, in the absence of acidosis or of hypoxia (see Ishige et al, 1987), sug gests mitochondrial dysfunction. It has been postulated that neurological dysfunc tion following CNS injury may result from a reduc tion in ATP levels (Sato et al, 1984), from in creased H+ concentration (Swanson 1969;Siesj6 and Wieloch, 1985), from increased lactate concen tration (Myers and Yamaguchi, 1977;Courten Myers et al, 1985), or from a combination of these factors (Rosner and Becker, 1984;Kim et al, 1985). No decrease in ATP levels was observed in this present study.…”

The Use of In Vivo Fluorescence Image Sequences to Indicate the Occurrence and Propagation of Transient Focal Depolarizations in Cerebral Ischemia

“…2, 3, and 5a-c) appears to us likely to repre sent this boundary. This suggestion is supported (a) by the finding (Strong et aI., 1988) of differing hy-drogen clearance reactivities to cortical stimulation to either side of a similarly oriented apparent boundary on the MG in the cat MCAO model and (b) by frequent observation of a sharp interface be tween normal and acidotic pH on the convexity of MG lfrozen coronal section imaging with umbellif erone fluorescence (Strong et aI., 1985)]; acidosis is widely regarded as an early change in focal cortical ischemia (Astrup et aI., 1977;Gibson et aI., 1983;Harris and Symon, 1984;Hossmann et aI., 1985;Kim et al, 1985).…”