Cerebrovascular responses to soman: time and dose dependent effects.
The effects of convulsant and subconvulsant doses of soman on cerebral blood flow (rCBF) and permeability-capillary surface area products (rPS) were examined in 15 brain regions at 1 hr, 24 hr and 1 week after injection in male, Sprague-Dawley rats. Brain histology was examined 3 days after injection. A convulsant dose of soman (70 micrograms/kg, sc) produced large increases in blood flow in all brain regions 1 hr after injection. Such elevations were still observed in 7/15 brain regions 1 day later and in 2/15 regions (septal area and basal ganglia) 1 week later. Similarly, rPS was significantly elevated in every brain region at 1 hr after injection, in 11/15 brain regions at 24 hr, and 4/15 regions 1 week later. Blood pressure peaked at 1 hr and remained well above control levels (115 mm Hg) for 5 hr after drug administration. A subconvulsant dose of soman (33 micrograms/kg) led to a significant, though less dramatic increase in blood flow in all brain regions within 1 hr but not at 1 day or 1 week after injection. In contrast, rPS increases were generally small except in hind-brain structures at 1 hr and 1 day after agent injection. By 1 week however, rPS values appeared to be rising generally and were significantly elevated in the olfactory bulbs and tubercle, as well as hindbrain regions. At this dose, blood pressures were unchanged from control levels (110-120 mm Hg) at all time periods. At 72 hr following injection of a convulsant dose of soman, severe and extensive cellular changes were found in 11/17 regions. After a subconvulsant dose, such abnormalities were still observed in 6/17 brain regions. The data strongly indicate that soman exposure can produce prolonged regional effects on cerebrovascular functions and neuronal integrity even in the absence of physiologic or behavioral evidence of seizure activity or sustained elevations of blood pressure.
Goldman
H
H
Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan 48201.
Berman
R F
RF
Hazlett
J
J
Murphy
S
S
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002199:Capillary Permeability / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000473:pathology; D012999:Soman / Q000494:pharmacology*; D013997:Time Factors
D002800:Cholinesterase Inhibitors; D012999:Soman