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Assessment of the effect of 2-chloroadenosine in normal rat brain using spin-labeled MRI measurement of perfusion
P M Kochanek1, K S Hendrich, C L Robertson
1Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, USA.
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.
Insights
2-chloroadenosine significantly increases cerebral blood flow (CBF) in rats, demonstrating a potent, dose-dependent, and sustained cerebrovasodilation. This finding supports its potential use in treating brain injuries by promoting blood flow.
Area of Science:
- Neuroscience
- Pharmacology
- Medical Imaging
Background:
- Adenosine analogs, like 2-chloroadenosine, are known potent cerebrovasodilators.
- Investigating their effects on cerebral blood flow (CBF) is crucial for understanding potential therapeutic applications.
Purpose of the Study:
- To investigate the spatial distribution, dose-response, and timing of 2-chloroadenosine's effect on CBF.
- To evaluate 2-chloroadenosine's cerebrovasodilatory effects using spin-labeled MRI after intraparenchymal injection in rats.
Main Methods:
- Intraparenchymal injection of 2-chloroadenosine (0.3, 6.0, or 12 nmoles) or saline vehicle into Sprague-Dawley rat brains (N=10).
- Serial quantification of CBF using spin-labeled MRI in regions of interest (ROI) around the injection site and ipsilateral hemisphere at approximately 90 and 180 minutes post-injection.
- Analysis of dose-response relationships and spatial distribution of vasodilatory effects.
Main Results:
- A marked increase in CBF was observed: 3.77- and 3.93-fold in the circular ROI, and 2.92- and 2.78-fold in the hemispheric ROI at 90 and 180 minutes after a 12-nmol injection, respectively.
- Linear dose-response relationships were evident at both time points in both ROIs (P < 0.01).
- Spin-labeling MRI confirmed potent, dose-dependent, and sustained vasodilation over large brain areas.
Conclusions:
- Intraparenchymal injection of 2-chloroadenosine induces potent, dose-dependent, and sustained cerebrovasodilation.
- The established treatment and imaging paradigm can facilitate research into promoting CBF for conditions like traumatic and ischemic brain injury.