Post-ischemic vascular adhesion protein-1 inhibition provides neuroprotection in a rat temporary middle cerebral artery occlusion model

作者：Watcharotayangul Jittiya; Mao Lizhen; Xu Haoliang; Vetri Francesco; Baughman Verna L; Paisansathan Chanannait; Pelligrino Dale A^*

来源：Journal of Neurochemistry, 2012, 123: 116-124.

DOI：10.1111/j.1471-4159.2012.07950.x

• adhesion
• extravasation
• leukocyte trafficking
• neuroprotection
• neutrophil
• semicarbazide-sensitive amine oxidase

We examined the neuroprotective efficacy associated with post-ischemic vascular adhesion protein-1 (VAP-1) blockade in rats subjected to transient (1 h) middle cerebral artery occlusion (MCAo). We compared saline-treated control rats to rats treated with a highly selective VAP-1 inhibitor, LJP-1586 [Z-3-fluoro-2-(4-methoxybenzyl) allylamine hydrochloride]. Initial intraperitoneal LJP-1586 (or saline control) treatments were delayed until 6 h or 12 h reperfusion. At 72-h reperfusion, LJP-1586-treated rats displayed 51% and 33% smaller infarct volumes, relative to their controls, in the 6- and 12-h treatment groups, respectively. However, only in the 6-h treatment group was the infarct volume reduction significant (p < 0.05). On the other hand, we observed significantly improved neurologic functions in both 6- and 12-h treatment groups, versus their matched controls (p < 0.05). Also, the effect of 6-h LJP-1586 treatment on post-ischemic leukocyte trafficking in pial venules overlying the ischemic cortex was evaluated using intravital microscopy. These experiments revealed that: 1) LJP-1586 did not affect intravascular leukocyte (largely neutrophil) adhesion, at least out to 12-h reperfusion; and 2) the onset of neutrophil extravasation, which occurred between 68-h reperfusion in control rats, was prevented by LJP-1586-treatment. In conclusion, in rats subjected to transient MCAo, selective VAP-1 pharmacologic blockade provided neuroprotection, with a prolonged therapeutic window of 612-h reperfusion.

• 出版日期2012-11