Statins decrease chondroitin sulfate proteoglycan expression and acute astrocyte activation in central nervous system injury.
Statins elicit numerous favorable effects on central nervous system (CNS) injury, including inhibition of the rhoA/ROCK pathway. In the present study, we show that statins decrease acute astrocyte activation in CNS injury, and decrease chondroitin sulfate proteoglycan (CSPG) levels in astrocyte cultures as well as CNS injury. CSPG levels decreased by up to 45% in simvastatin-treated astrocyte cultures compared to control cultures. In simvastatin-treated animals, CSPG levels declined by 60% 8 days after brain stab injury, and by 62-64% 4 weeks after spinal cord injury (SCI). Glial fibrillary acid protein (GFAP) levels decreased in brain stab at 8 days after surgery/intervention, suggesting that statins produce a decrease in astrocyte activation. Attenuation of astrocyte activation may contribute to the decline in CSPG levels. However, there are likely other contributing factors, since GFAP levels were not a contributing factor in the decline of CSPG levels in astrocyte cultures. Robust locomotor improvements were not observed with any treatment. The numerous beneficial effects of statins on CNS injury render them an attractive candidate in the treatment of CNS injury.
Holmberg
Eric
E
Spinal Cord Society Research Center, 2401 Research Boulevard., Suite 206, Fort Collins, CO 80526-1826, USA. eholmberg@scs.cbeyond.com
Zhang
Shu-xin
SX
Sarmiere
Patrick D
PD
Kluge
Bridget R
BR
White
Jason T
JT
Doolen
Suzanne
S
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D001930:Brain Injuries / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019821:Simvastatin / Q000494:pharmacology*; D013119:Spinal Cord Injuries / Q000378:metabolism*
D011508:Chondroitin Sulfate Proteoglycans; D005904:Glial Fibrillary Acidic Protein; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin