Scavenger Receptor Class-A Has a Central Role in Cerebral Ischemia–Reperfusion Injury

Abstract

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 À/À 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 À/À mice was significantly reduced by 63.9% compared with WT mice after cerebral I/R. In SR-A À/À 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 0 -deoxyuridine 5 0 -triphosphate-biotin nick end labelingpositive apoptotic cells were significantly increased in WT mice after cerebral I/R, but not in SR-A À/À mice. Cerebral I/R increased nuclear factor-jB activation in WT mice, but not in SR-A À/À 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.

Toll-Like Receptors: New Players in Myocardial Ischemia/Reperfusion Injury

“…Interestingly, either deficiency of TLR4 (27,73,74) or TLR2 (101) protected the brain from cerebral I/R injury. Similar observations have been found in either CD36 (33,89,96) or SR-A knockout mice (112). Deficiency of either CD36 (33, 89, 96) or SR-A (112) protects the brain from cerebral I/R injury.…”

Increased stability of phosphatase and tensin homolog by intermedin leading to scavenger receptor A inhibition of macrophages reduces atherosclerosis in apolipoprotein E-deficient mice

“…Studies of SR-A −/− mice have shown that SR-A enhances the pathogenesis of diabetic nephropathy [42], pulmonary Mycobacterium tuberculosis infection [43], cerebral ischemia-reperfusion injury [44], and the development of colitis and Alzheimer disease [16,17,45], and SR-A-positive macrophages play a pivotal role in the progression of ovarian and prostate cancers [14,15]. Thus, our finding of IMD downregulating SR-A expression may be helpful in treating these diseases.…”

Scavenger Receptor-A (CD204): A Two-Edged Sword in Health and Disease

“…While there are differences in the experimental models employed by Xu 111 and Lu 112 both studies led to the same conclusion: SR-A contributes to brain injury after ischemia and/or reperfusion. In support of this concept, Murgas et al used SR-A −/− astrocytes in vitro to demonstrate that the presence of SR-A contributes to the neuro-inflammatory response (Table 3).…”

“…112 After 60 minutes of occlusion, the blockage was removed and reperfusion allowed for varying periods of time. SR-A −/− mice showed less cerebral damage (smaller infarct size) after ischemia and decreased cerebral and systemic inflammatory response when compared with WT mice with cerebral ischemia/reperfusion.…”