7 beta-hydroxycholesterol and 7 beta-hydroxycholesteryl-3-esters reduce the extent of reactive gliosis caused by an electrolytic lesion in rat brain.
Electrolytic lesions performed in brain cortex of six-day-old or adult rats resulted in the appearance of many reactive astrocytes around the injury site after a postoperative delay of eight days. They were revealed by immunohistochemistry using antibodies against glial fibrillary acidic protein. Injection of tritiated thymidine 24 h prior to autopsy indicated that, in neonates, 50% of the reactive astrocytes were proliferating. Infusion of 2 microliters of liposome suspension made of phosphatidylcholine and a monosialoganglioside, in the injury site, immediately after the electrolytic lesion did not modify the extent of the reactive gliosis. Liposomes containing 3 nmol of either 7 beta-hydroxycholesterol, 7 beta-hydroxycholesteryl-3-stearate or 7 beta-hydroxycholesteryl-3-oleate reduced by about 50% the intensity of the reactive gliosis in the frontal cortex of six-day-old rats and by 40% the number of dividing astrocytes. In the adult rat cortex the intensity of the glial reaction was also decreased by 30% by 15 nmol 7 beta-hydroxycholesteryl-3-oleate. Further investigations demonstrated that it is the 7 beta-hydroxy function which is needed for the biological activity of these oxysterols. These findings, which demonstrate anti-proliferative and anti-inflammatory properties of 7 beta-hydroxycholesterol on astrocytes, facilitate the future investigation of the influence of reactive gliosis on functional recovery following brain injury. This anti-proliferative property could also be used in other kinds of pathologies involving glial cell proliferation, such as glioblastomas.
Bochelen
D
D
Laboratoire de Neurobiologie Moléculaire des Interactions Cellulaires, CNRS, Strasbourg, France.
Eclancher
F
F
Kupferberg
A
A
Privat
A
A
Mersel
M
M
D000818:Animals; D001253:Astrocytes / Q000473:pathology*; D001345:Autoradiography; D001930:Brain Injuries / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002788:Cholesterol Esters / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000276:immunology; D005911:Gliosis / Q000473:pathology / Q000517:prevention & control*; D006888:Hydroxycholesterols / Q000494:pharmacology*; D007150:Immunohistochemistry; D008081:Liposomes; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D002788:Cholesterol Esters; D005904:Glial Fibrillary Acidic Protein; D006888:Hydroxycholesterols; D008081:Liposomes; C011724:cholest-5-en-3 beta,7 alpha-diol