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Attenuation of ischemia-induced extracellular adenosine accumulation by homocysteine
1Department of Pathology, School of Medicine and Biomedical Sciences, State University of New York, Buffalo 14215.
Insights
Homocysteine reduces basal interstitial fluid adenosine and cerebral blood flow. It also lessens the rise in adenosine during ischemia and impairs blood flow recovery after the event.
Area of Science:
- Neuroscience
- Cardiovascular Science
- Biochemistry
Background:
- Homocysteine is implicated in various neurological conditions.
- Adenosine plays a crucial role in regulating cerebral blood flow (CBF).
- The interaction between homocysteine, adenosine, and CBF during ischemia is not fully understood.
Purpose of the Study:
- To investigate the impact of homocysteine on interstitial fluid (ISF) adenosine levels.
- To assess the effects of homocysteine on cerebral blood flow (CBF) before, during, and after ischemic events.
- To elucidate the mechanism by which homocysteine influences adenosine metabolism and CBF.
Main Methods:
- Utilized microdialysis probes in halothane-anesthetized rats to measure local CBF and ISF adenosine.
- Administered L-homocysteine thiolactone locally to one hemisphere.
- Induced transient cerebral ischemia via bilateral carotid occlusion and hemorrhage, followed by reperfusion.
Main Results:
- Homocysteine decreased basal ISF adenosine and CBF.
- The ischemia-induced increase in ISF adenosine was attenuated on the side where homocysteine was administered.
- CBF remained lower on the homocysteine-treated side throughout the reperfusion period, indicating reduced hyperemia.
Conclusions:
- Homocysteine significantly alters adenosine levels and reduces cerebral blood flow.
- Homocysteine interferes with the brain's natural response to ischemia and reperfusion.
- These findings suggest a potential role for homocysteine in cerebrovascular dysfunction during ischemic conditions.
Abstract:
The purpose of this study was to determine the effects of homocysteine, which consumes intracellular adenosine via formation of S-adenosylhomocysteine, on interstitial fluid (ISF) adenosine and cerebral blood flow (CBF) before, during, and after cerebral ischemia. Microdialysis probes, used to measure local CBF (H2 clearance) and to sample ISF, were implanted bilaterally into the caudate nucleus of halothane-anesthetized rats (n = 8). L-Homocysteine thiolactone was administered locally via one of the probes. Animals were exposed to 20 min of ischemia, induced by bilateral carotid occlusion plus hemorrhage to an arterial blood pressure of 50 mm Hg, followed by 60 min of reperfusion. Before ischemia, CBF and dialysate adenosine were decreased with homocysteine. During ischemia and early reperfusion, dialysate purine metabolites increased on both sides of the brain; however, the ischemia-induced increase in adenosine was attenuated on the side of local homocysteine. CBF was lower on the side of homocysteine throughout reperfusion. These data demonstrate that homocysteine (a) decreases basal ISF adenosine and CBF, (b) attenuates the increase in dialysate adenosine during ischemia, and (c) reduces hyperemia during early reperfusion.