We studied the effect of brain and spinal cord injury induced by fluid-perc
ussion on the local synthesis of neurosteroids as measured by a gas-chromat
ographic/mass-spectrometric method. In the nervous system of sham operated
rats i.v. infusion of pregnenolone (PREGN)-sulfate results in a 2-4 fold in
crease in PREGN, progesterone (PROG), 5alpha-dehydroprogesterone (5 alpha-D
HP) and 3alpha-hydroxy-5alpha-pregnan-20-one (3 alpha 5 alpha-THP, allopreg
nanolone) concentrations, as compared to vehicle treated rats. When PREGN-s
ulfate was infused 1,3 or 7 days after brain or spinal cord injury it was o
bserved a large time-dependent increase of FROG, 5 alpha-DHP and 3 alpha 5
alpha-THP levels in the peri-focal but not in the focal site. This increase
in neurosteroids content may be due essentially to the glial cells hyperpl
asia in the peri-focal area and to an activation of the pathways involved i
n the metabolism of PREGN-sulfate to FROG, 5 alpha-DHP and 3 alpha 5 alpha-
THP. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.