The treatment of traumatic brain injury with velcade.
Traumatic brain injury (TBI) elicits a strong inflammatory response that contributes to the acute pathological processes seen following TBI, including cerebral edema and disruption of the blood-brain barrier (BBB), in addition to longer-term neurological damage and cognitive impairment. Proteasome inhibitors reduce vascular thrombotic and inflammatory events and consequently protect vascular function. In the present study we evaluated the neuroprotective effect of Velcade (bortezomib), a potent and selective inhibitor of proteasomes, which is in clinical use for the treatment of multiple myeloma. When administered within 2 h after TBI onset, Velcade reduced inflammatory responses, lesion volume, and neurological functional deficits, and enhanced neuronal survival. Western blot and ELISA showed that Velcade decreased the expression of NF-κB. These results suggest that in the experimental setting, Velcade is an effective neuroprotective agent for the treatment of TBI.
Qu
Changsheng
C
Department of Neurosurgery, Henry Ford Health System, Detroit, Michigan 48202, USA.
Mahmood
Asim
A
Ning
Ruizhuo
R
Xiong
Ye
Y
Zhang
Li
L
Chen
Jieli
J
Jiang
Hao
H
Chopp
Michael
M
D000818:Animals; D001897:Boronic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D000069286:Bortezomib; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D008297:Male; D011719:Pyrazines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib