Gj. Lees et W. Leong, BRAIN-LESIONS INDUCED BY SPECIFIC AND NONSPECIFIC INHIBITORS OF SODIUM-POTASSIUM ATPASE, Brain research, 649(1-2), 1994, pp. 225-233
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.