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1572595 
Journal Article 
The Chronic Protective Effects of Limb Remote Preconditioning and the Underlying Mechanisms Involved in Inflammatory Factors in Rat Stroke 
Wei, D; Ren, C; Chen, X; Zhao, H 
2012 
1 
PLoS ONE
EISSN: 1932-6203 
7 
2 
22347410 
WOS:000302730100029 
We recently demonstrated that limb remote preconditioning
(LRP) protects against focal ischemia measured 2 days post-stroke. Here, we studied whether LRP
provides long-term protection and improves neurological function. We also investigated whether
LRP transmits its protective signaling via the afferent nerve pathways from the preconditioned
limb to the ischemic brain and whether inflammatory factors are involved in LRP, including the
novel galectin-9/Tim-3 inflammatory cell signaling pathway, which induces cell death in
lymphocytes. LRP in the left hind femoral artery was performed immediately before stroke. LRP
reduced brain injury size both at 2 days and 60 days post-stroke and improved behavioral outcomes
for up to 2 months. The sensory nerve inhibitors capsaicin and hexamethonium, a ganglion blocker,
abolished the protective effects of LRP. In addition, LRP inhibited edema formation and blood-
brain barrier (BBB) permeability measured 2 days post-stroke. Western blot and immunostaining
analysis showed that LRP inhibited protein expression of both galectin-9 and T-cell
immunoglobulin domain and mucin domain 3 (Tim-3), which were increased after stroke. In addition,
LRP decreased iNOS and nitrotyrosine protein expression after stroke. In conclusion, LRP executes
long-term protective effects against stroke and may block brain injury by inhibiting activities
of the galectin-9/Tim-3 pathway, iNOS, and nitrotyrosine.