Influence of blood glucose level on postischemic recovery of the brain function and energy metabolism, and on ischemic neuronal change

Lactate accumulates in the brain tissue during ischemia due to anaerobic glycolysis and produces lactic acidosis. It is suggested that lactic acidosis is an important causative factor for ischemic cell damage. In complete or severe incomplete cerebral ischemia, concentrations of cerebral tissue lactate are influenced by levels of blood glucose. This study explores the influence of levels of blood glucose in the cerebral ischemic rats on postischemic recovery of the tissue energy metabolism and EEG, on the neuropathology, and on the accumulation of free fatty acids in brain tissue during ischemia. Severe incomplete cerebral ischemia was induced by four-vessel occlusion and reducing the systolic arterial pressure to 100 mmHg and recirculation was started by release of bilateral carotid artery clamping and restoration of arterial blood pressue to preischemic level. The EEG was continuously recorded from gold-coated screws inserted bilaterally in the parietal bones with the tips in extradural position, against a reference inserted prefrontal bone. The brains were frozen in situ with liquid nitrogen and then chiselled out during irrigation with liquid nitrogen. Concentrations of ATP and free fatty acids in brain tissue were determined with high performance liquid chromatography. Immediately after the end of 120 minutes of recirculation period, the brains were removed and fixed in formalin and stained by hematoxylin-eosin and luxol fast blue methods to observe ischemic changes. Experimental animals were divided into 3 groups according to their preischemic blood glucose levels as follows. Group 1 animals were normoglycemic controls (blood glucose levels 116-196 mg/dl, mean 149 mg/dl). Group 2 animals were injected 0.5 ml of 50% glucose solution before ischemia (blood glucose levels 316-430 mg/dl, mean 373 mg/dl). Group 3 animals were injected 2 ml of 50% glucose solution before ischemia (blood glucose levels 684-954 mg/dl, mean 788 mg/dl). After four-vessel occlusion associated with mild hypotension, the EEG became isolectric within 10-20 seconds in all experimental animals. Following 30 minutes of ischemia, a spontaneous EEG returned after 17-35 minutes of recirculation in group 1 animals and after 40-63 minutes in group 2 animals. At the end of the 120 minutes recirculation periods, the EEG activity in group 1 animals showed better recovery than in group 2. Group 3 animals did not recover any significant EEG activity or showed only a burst suppression pattern.