Scavenger receptor class-A has a central role in cerebral ischemia-reperfusion injury.
The innate immune response is involved in the pathophysiology of cerebral ischemia-reperfusion (I/R) injury. Recent evidence suggests that scavenger receptors have a role in the induction of innate immunity. In this study, we examined the role of scavenger receptor A (SR-A) in focal cerebral I/R injury. Both SR-A(-/-) mice (n=10) and age-matched wild-type (WT) mice (n=9) were subjected to focal cerebral ischemia (60 minutes), followed by reperfusion (for 24 hours). Infarct size was determined by TTC (triphenyltetrazolium chloride) staining. The morphology of neurons in the brain sections was examined by Nissl's staining. Activation of intracellular signaling was analyzed by western blot. Cerebral infarct size in SR-A(-/-) mice was significantly reduced by 63.9% compared with WT mice after cerebral I/R. In SR-A(-/-) mice, there was less neuronal damage in the hippocampus compared with WT mice. Levels of FasL, Fas, FADD, caspase-3 activity, and terminal deoynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling-positive apoptotic cells were significantly increased in WT mice after cerebral I/R, but not in SR-A(-/-) mice. Cerebral I/R increased nuclear factor-κB activation in WT mice, but not in SR-A(-/-) mice. These data suggest that SR-A has a central role in cerebral I/R injury and that suppression of SR-A may be a useful approach for ameliorating brain injury in stroke patients.
Lu
Chen
C
Department of Surgery, East Tennessee State University, Johnson City, Tennessee, USA. Li@etsu.edu
Hua
Fang
F
Liu
Li
L
Ha
Tuanzhu
T
Kalbfleisch
John
J
Schweitzer
John
J
Kelley
Jim
J
Kao
Race
R
Williams
David
D
Li
Chuanfu
C
D000818:Animals; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism*; D051117:Scavenger Receptors, Class A / Q000172:deficiency / Q000378:metabolism*
D016328:NF-kappa B; D051117:Scavenger Receptors, Class A