Increased neurosteroids synthesis after brain and spinal cord injury in rats.
We studied the effect of brain and spinal cord injury induced by fluid-percussion on the local synthesis of neurosteroids as measured by a gas-chromatographic/mass-spectrometric method. In the nervous system of sham operated rats i.v. infusion of pregnenolone (PREGN)-sulfate results in a 2-4 fold increase in PREGN, progesterone (PROG), 5alpha-dehydroprogesterone (5alpha-DHP) and 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha5alpha-THP, allopregnanolone) concentrations, as compared to vehicle treated rats. When PREGN-sulfate was infused 1, 3 or 7 days after brain or spinal cord injury it was observed a large time-dependent increase of PROG, 5alpha-DHP and 3alpha5alpha-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 hyperplasia in the peri-focal area and to an activation of the pathways involved in the metabolism of PREGN-sulfate to PROG, 5alpha-DHP and 3alpha5alpha-THP.
di Michele
F
F
IRCCS Santa Lucia, Rome, Italy.
Lekieffre
D
D
Pasini
A
A
Bernardi
G
G
Benavides
J
J
Romeo
E
E
D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology*; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D018696:Neuroprotective Agents / Q000378:metabolism; D011284:Pregnenolone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000502:physiology; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D013256:Steroids / Q000032:analysis / Q000096:biosynthesis*; D013997:Time Factors
D018696:Neuroprotective Agents; D013256:Steroids; D011284:Pregnenolone