ABSTRACT
The pathophysiology of uremic encephalopathy and the various cerebral disorders associated with uremia are poorly understood. The aim of the present work was to study the role played by the major uremic toxins [non protein nitrogen, urea, uric acid, creatinine and phenols] in this regard. This was achieved by determining their concentrations in the plasma, the cerebrum, cerebellum, brain stem and skeletal muscles of rats with experimental uremia induced by bilateral ligation of both ureters for 48 hours. Results revealed that uremic rats showed an apparent alteration in alertness and appeared drowsy compared with their pre-fed controls suggesting an early stage of metabolic encephalopathy. It was evident from the study that the blood brain barrier was broken in uremia as there was high concentration of the studied uremic metabolites in the brain parts of uremic animals compared with controls. However, this barrier was not totally ruptured because the concentration of any given metabolite was higher in the skeletal muscle than the brain parts. The affinity of the different brain parts to the same metabolite was also different. So, it was justified to postulate that the composite picture of the uremic patients may be due to the variability in the concentrations of these studied toxins and/or others in the different parts of the brain resulting in disturbance of their normal function. The effect of the metabolites studied on the nervous system was also reviewed