title: Assessment of the effect of 2-chloroadenosine in normal rat brain using spin-labeled MRI measurement of perfusion.
abstract: Adenosine analogs such as 2-chloroadenosine are potent cerebrovasodilators. Spin-labeled MRI was used to investigate the spatial distribution, dose-response, and timing of the effect of 2-chloroadenosine on cerebral blood flow (CBF) after intraparenchymal injection into rat brain. Sprague-Dawley rats (N = 10) were injected with 2-chloroadenosine at doses of 0.3, 6.0, or 12 nmoles, or saline vehicle (2-4 microL). CBF was serially quantified in a slice through the injection site in a circular (3.6 mm diameter) region of interest (ROI) around the injection and in ipsilateral hemispheric ROIs at approximately 90 min and approximately 180 min. Marked 3.77- and 3.93-fold increases in CBF (vs. vehicle) were seen in the circular ROI at approximately 90 min and approximately 180 min after 12-nmol injection, respectively. Similarly, 2.92- and 2.78-fold increases in hemispheric CBF were observed at approximately 90 min and approximately 180 min, respectively, after injection of 12 nmoles. Linear dose-response relationships were observed at both times after injection in both ROIs (all P < 0.01). Spin-labeling MRI assessment revealed that parenchymal injection of 2-chloroadenosine produces potent, dose-dependent, and sustained vasodilation over large areas of brain. This treatment and imaging paradigm should facilitate investigation of the effect of CBF promotion in models of traumatic and ischemic brain injury.
authors.affiliation: Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: P M
authors.initials: PM
authors.lastname: Kochanek
authors.forename: K S
authors.initials: KS
authors.lastname: Hendrich
authors.forename: C L
authors.initials: CL
authors.lastname: Robertson
authors.forename: D S
authors.initials: DS
authors.lastname: Williams
authors.forename: J A
authors.initials: JA
authors.lastname: Melick
authors.forename: C
authors.initials: C
authors.lastname: Ho
authors.forename: D W
authors.initials: DW
authors.lastname: Marion
authors.forename: E K
authors.initials: EK
authors.lastname: Jackson
mesh_terms: D015762:2-Chloroadenosine / Q000494:pharmacology*; D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016014:Linear Models; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013113:Spin Labels
chemical_list: D013113:Spin Labels; D015762:2-Chloroadenosine