Changes of the Na/K ATPase activity in the cerebral cortical microvessels of rat after single intraperitoneal administration of mercuric chloride: histochemical demonstration with light and electron microscopy.
Since inorganic mercury salts only poorly penetrate the cerebral microvascular endothelial cells comprising the blood-brain barrier (BBB), their neurotoxicity may be predicted to result from interference with BBB transport enzymes. In the present study, we tested the effect of mercuric chloride (HgCl2) on Na+/K+ ATPase activity, a key enzyme involved in the ion transport in and out of the brain. Routine histochemical staining in conjunction with light and electron microscopy was used to evaluate the changes in the Na+/K+ ATPase activity in cerebral cortical microvessels of rats who received a single intraperitoneal injection of 6 mg/kg HgCl2. At 1 h after HgCl2 administration, light microscopy revealed uniform reduction of the Na+/K+ ATPase reaction in all cortical layers. Electron microscopy confirmed the enzyme reaction to be very weak to completely absent in both the luminal and abluminal endothelial cell membranes, and the luminal plasmalemma showed invaginations and pinocytic vesicles indicative of changes in its transport functions. The enzyme inhibition coincided with, and was likely to contribute to, profound perivascular swelling, involving mainly the astrocytic endfeet. The enzyme activity showed a partial recovery 18 h after HgCl2 treatment, mainly in cortical layers II and III. After 5 days, the recovery of the enzyme activity appeared complete as observed by light and electron microscopy. The recovery of the microvascular Na+/K+ ATPase coincided with the appearance of a strongly positive Na+/K+ ATPase reaction in the adjacent astrocytic processes and with the diminution of perivascular swelling.
Department of Neuropathology, Polish Academy of Sciences, Warsaw.
G
G
Szumańska
R
R
Gadamski
J
J
Albrecht
D000818:Animals; D001253:Astrocytes / Q000201:enzymology / Q000648:ultrastructure; D002196:Capillaries / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D002462:Cell Membrane / Q000201:enzymology / Q000648:ultrastructure; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D006651:Histocytochemistry; D007274:Injections, Intraperitoneal; D008297:Male; D008627:Mercuric Chloride / Q000008:administration & dosage / Q000494:pharmacology*; D008854:Microscopy, Electron; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D008627:Mercuric Chloride; D000254:Sodium-Potassium-Exchanging ATPase