These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Vascular adhesion protein-1 plays an important role in postischemic inflammation and neuropathology in diabetic, estrogen-treated ovariectomized female rats subjected to transient forebrain ischemia.
    Author: Xu HL, Salter-Cid L, Linnik MD, Wang EY, Paisansathan C, Pelligrino DA.
    Journal: J Pharmacol Exp Ther; 2006 Apr; 317(1):19-29. PubMed ID: 16339390.
    Abstract:
    Endothelial vascular adhesion protein-1 (VAP-1) facilitates leukocyte adhesion and infiltration. This relates partly to the function of VAP-1 as a semicarbazide-sensitive amine oxidase (SSAO). We examined the effects of VAP-1/SSAO inhibition [via LJP-1207 (N'-(2-phenyl-allyl)-hydrazine hydrochloride)] on pial venular leukocyte adhesion and infiltration (at 2-10 h of reperfusion) and neuropathology (at 72 h of reperfusion) after transient forebrain ischemia (TFI). A model associated with increased postischemic inflammation was used-i.e., diabetic ovariectomized (OVX) female rats given chronic estrogen replacement therapy (ERT). We compared rats treated, either at the onset or at 6 h of reperfusion, with saline or LJP-1207. Additional rats, rendered neutropenic 24 h before TFI, were studied. In saline-treated controls, intravascular accumulation of adherent leukocytes gradually increased, reaching 15 to 20% of the venular area, at which point neutrophil infiltration commenced (at approximately 6 h). In the rats given LJP-1207 at the onset of reperfusion, limited neutrophil adhesion ( approximately 5% maximum) and no infiltration were observed. These results generally paralleled those in neutropenic rats. In rats treated at 6 h of reperfusion, the pattern of neutrophil adhesion was similar to that of the saline-treated group up to 6 h, but further infiltration was essentially prevented. Neurologic outcomes and histopathology were similar to one another in the LJP-1207-treated and neutropenic groups and significantly improved over those in saline-treated controls. Thus, VAP-1-mediated post-TFI leukocyte adhesion/infiltration in diabetic OVX females given chronic ERT contributes substantially to neuropathology. One implication is that specifically preventing leukocyte infiltration provides a substantial measure of neuroprotection. This could explain the finding of LJP-1207 having at least a 6-h therapeutic window in this model.
    [Abstract] [Full Text] [Related] [New Search]