title: Longitudinal assessment of imatinib's effect on the blood-brain barrier after ischemia/reperfusion injury with permeability MRI.
abstract: Acute ischemic stroke (AIS) often results in degeneration of the blood-brain barrier (BBB), which can lead to vasogenic edema and an increased risk of intracerebral hemorrhage. Imatinib is an agent that may be able to protect the BBB and reduce the risk of the harmful consequences of BBB degeneration. We sought to measure the effect of Imatinib on the BBB after experimental stroke longitudinally in vivo with permeability dynamic contrast-enhanced MRI. Ischemia/reperfusion injury was induced with a transient middle cerebral artery occlusion surgery. Rats were given Imatinib at 2 and 20 h after stroke onset. Post-assessment included neurologic functioning, MR imaging, Evans Blue extravasation, Western blot, and immunohistology assay. Imatinib protected the BBB by 24 h but failed to decrease BBB permeability at an earlier time-point. Imatinib also reduced infarct volume, edema, and improved neurologic functioning by 24 h. Rats treated with Imatinib also had a higher expression of the BBB structural protein Zona ocludens-1 and a reduction in nuclear factor-kappa beta (NF-κβ) activation. Imatinib is a promising agent to protect the BBB after AIS, but its effect on the BBB may not become prominent until 24 h after the onset of ischemia. This finding may help elucidate Imatinib's role in the clinical management of AIS and influence future study designs.
authors.affiliation: Department of Physiology and Experimental Medicine, Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Zamir
authors.initials: Z
authors.lastname: Merali
authors.forename: Jackie
authors.initials: J
authors.lastname: Leung
authors.forename: D
authors.initials: D
authors.lastname: Mikulis
authors.forename: F
authors.initials: F
authors.lastname: Silver
authors.forename: Andrea
authors.initials: A
authors.lastname: Kassner
mesh_terms: D000818:Animals; D001549:Benzamides / Q000008:administration & dosage*; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism*; D002545:Brain Ischemia / Q000150:complications* / Q000188:drug therapy; D000068877:Imatinib Mesylate; D020244:Infarction, Middle Cerebral Artery; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D010539:Permeability; D010879:Piperazines / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications* / Q000188:drug therapy; D020521:Stroke / Q000150:complications* / Q000188:drug therapy; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D001549:Benzamides; D016328:NF-kappa B; D010879:Piperazines; D011743:Pyrimidines; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; D000068877:Imatinib Mesylate