Interrelation between cerebral energy metabolism and behaviour in a rat model of permanent brain vessel occlusion

The present study investigates the interrelation between cerebral energy me tabolism and memory capacities after acute and permanent occlusions of caro tid and vertebral arteries in adult Wistar rats (n = 60). Tissue ATP, phosp hocreatine, ADP, AMP and adenosine concentrations were determined in rat br ain by high-pressure liquid chromatography (HPLC) analysis. Lactate and pyr uvate were measured spectrophotometrically. Rats underwent psychometric tes ting by means of a holeboard test, closed field activity, and passive avoid ance behaviour. Acute cerebral ischaemia was associated with a substantial deficit in energy load (- 50%). Cortical adenosine and lactate exhibited a 7- and a 10-fold increase, respectively, in concentration. After 2 weeks of four-vessel occlusion, cortical ATP and phosphocreatine showed a partial e nhancement in their concentrations if compared with acute ischaemia. Conseq uently, energy load (mu mol/g) increased from 0.59 to 1.42 in cerebral cort ex and from 0.58 to 1.14 in hippocampus under conditions of acute and perma nent ischaemia, respectively. While lactate was normalized, adenosine showe d a 2-fold increase in its cortical concentration. All animals improved the ir abilities in learning, memory and cognition after a 7-day training perio d. Acute vessel occlusion severely decreased working memory (WM), reference memory (RM) and locomotor activity. Simultaneously, the passive avoidance test showed a significant reduction in latency time from 247 +/- 85 s (sham ) to 145 +/- 132 s. The partial improvement in brain energy state was accom panied by a relative improvement in WM and RM, although both memory capacit ies remained significantly lower than in controls. The data of the present study demonstrate a Linear relationship between cerebral energy metabolism and brain memory capacities after acute and permanent vessel occlusions in rats. (C) 1999 Elsevier Science B.V. All rights reserved.