TY - JOUR
T1 - Protection from brain damage and bacterial infection in murine stroke by the novel caspase-inhibitor Q-VD-OPH
AU - Braun, Johann Sebastian
AU - Prass, Konstantin
AU - Dirnagl, Ulrich
AU - Meisel, Andreas
AU - Meisel, Christian
PY - 2007/8
Y1 - 2007/8
N2 - Infarction size and infections are important determinants of stroke outcome in humans. Bacterial infections are promoted by stroke-induced immunodeficiency which in experimental stroke is mainly characterized by extensive lymphocyte apoptosis and dysfunction. Pharmacological inhibition of caspases may improve stroke outcome not only by reducing apoptotic brain damage but also by attenuating stroke-induced immunodeficiency. We investigated the effects of systemic administration of the novel, non-toxic caspase-inhibitor quinolyl-valyl-O-methylaspartyl-[-2,6-difluorophenoxy]-methyl ketone (Q-VD-OPH) on stroke-induced neuronal and lymphocyte apoptosis, susceptibility to infections, and mortality in a murine model of stroke induced by middle cerebral artery occlusion (MCAO). Q-VD-OPH reduced ischemic brain damage and stroke-induced programmed cell death in thymus and spleen, decreased susceptibility to post-stroke bacteremia, and improved survival. Therefore, Q-VD-OPH may be a promising therapeutic agent in stroke.
AB - Infarction size and infections are important determinants of stroke outcome in humans. Bacterial infections are promoted by stroke-induced immunodeficiency which in experimental stroke is mainly characterized by extensive lymphocyte apoptosis and dysfunction. Pharmacological inhibition of caspases may improve stroke outcome not only by reducing apoptotic brain damage but also by attenuating stroke-induced immunodeficiency. We investigated the effects of systemic administration of the novel, non-toxic caspase-inhibitor quinolyl-valyl-O-methylaspartyl-[-2,6-difluorophenoxy]-methyl ketone (Q-VD-OPH) on stroke-induced neuronal and lymphocyte apoptosis, susceptibility to infections, and mortality in a murine model of stroke induced by middle cerebral artery occlusion (MCAO). Q-VD-OPH reduced ischemic brain damage and stroke-induced programmed cell death in thymus and spleen, decreased susceptibility to post-stroke bacteremia, and improved survival. Therefore, Q-VD-OPH may be a promising therapeutic agent in stroke.
KW - Caspases
KW - Infection
KW - Ischemia
KW - MCAO
KW - Q-VD-OPH
KW - Stroke
UR - http://www.scopus.com/inward/record.url?scp=34547124824&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34547124824&partnerID=8YFLogxK
U2 - 10.1016/j.expneurol.2007.03.032
DO - 10.1016/j.expneurol.2007.03.032
M3 - Article
C2 - 17585906
AN - SCOPUS:34547124824
SN - 0014-4886
VL - 206
SP - 183
EP - 191
JO - Experimental Neurology
JF - Experimental Neurology
IS - 2
ER -