BRAIN-LESIONS INDUCED BY SPECIFIC AND NONSPECIFIC INHIBITORS OF SODIUM-POTASSIUM ATPASE

The cytotoxicity in the brain of potent selective and non-selective in hibitors of Na+/K+ ATPase has been assessed. Following injection of ca rdiac glycosides into the dorsal hippocampus of rats, the extent of ne uronal loss roughly paralleled their potencies as inhibitors of the en zyme. Dihydroouabain was less potent than ouabain as a cytotoxin by an order of magnitude, similar to their relative affinities for Na+/K+ A TPase. The non-specific inhibitors, melittin, erythrosin B and zinc (c hloride) were less neurocytotoxic than the selective inhibitors having equivalent potencies. The toxicity of a low dose of ouabain appeared to be selective for neuronal perikarya as staining for acetylcholinest erase (present on the nerve terminals of the afferent cholinergic inne rvation) was unaffected. A higher dose of ouabain caused a non-specifi c necrosis including damage to the neuropil and a loss of cholinestera se staining. Concurrently, there was an invasion of the tissue by cell s resembling foaming macrophages. Other inhibitors of the enzyme cause d a mixed pathology with both types of responses evident. It is sugges ted that the pathological response may depend on the relative degrees to which the glial and neuronal activities of the enzyme are affected.