Assessment of the effect of 2-chloroadenosine in normal rat brain using spin-labeled MRI measurement of perfusion

Adenosine analogs such as 2-chloroadenosine are potent cerebrovasodilators. Spin-labeled MRI was used to investigate the spatial distribution, dose-re sponse, and timing of the effect of 2-chloroadenosine on cerebral blood flo w (CBF) after intraparenchymal injection into rat brain. Sprague-Dawley rat s (N = 10) were injected with 2-chloroadenosine at doses of 0.3, 6.0, or 12 nmoles, or saline vehicle (2-4 muL) CBF was serially quantified in a slice through the injection site in a circular (3.6 mm diameter) region of inter est (ROI) around the injection and in ipsilateral hemispheric ROIs at simil ar to 90 min and similar to 180 min. Marked 3.17- and 3.93-fold increases i n CBF (vs, vehicle) were seen in the circular ROI at similar to 90 min and similar to 180 min after 12-nmol injection, respectively. Similarly, 2.92- and 2.78-fold increases in hemispheric CBF were observed at similar to 90 m in and similar to 180 min, respectively, after injection of 12 nmoles, Line ar dose-response relationships were observed at both times after injection in both ROIs (all P < 0.01), Spin-labeling MRI assessment revealed that par enchymal injection of 2-chloroadenosine produces potent, dose-dependent, an d sustained vasodilation over large areas of brain. This treatment and imag ing paradigm should facilitate investigation of the effect of CBF promotion in models of traumatic and ischemic brain injury, (C) 2001 Wiley-Liss, Inc .