Effect of mivazerol, a alpha-agonist, on striatal norepinephrine concentration during transient forebrain ischemia in
T Kimura1, K Sato, T Nishikawa
1Department of Anesthesia and Intensive Care Medicine, Akita University School of Medicine, Akita, Japan. kimtetsu@doc.med.akita-u.ac.jp
Background:
We have previously reported that mivazerol, a alpha(2)-agonist, possibly provides neuroprotection against transient forebrain ischemia in rats. This study was designed to investigate the ability of mivazerol to attenuate ischemia-induced increase in striatal norepinephrine concentration after transient forebrain ischemia in rats.
Methods:
Male Sprague-Dawley rats, anesthetized with halothane, were assigned to one of three groups (n=10 each); control (C, normal saline 1 ml/kg), mivazerol 20 microg/kg (M20), and 40 microg/kg (M40) groups. Monitored variables included temporal muscle temperature (maintained at 37.5+/-0.1 degrees C), electroencephalogram, systolic/diastolic blood pressure, heart rate, arterial blood gases, and blood glucose concentrations. Thirty minutes after subcutaneous drug administration, forebrain ischemia was induced with hemorrhagic hypotension (systolic arterial pressure: 40-50 mmHg) and bilateral carotid artery occlusion for 10 min, and then the brain was reperfused. Norepinephrine concentration in the interstitial fluids in the striatum was analyzed using in vivo microdialysis in combination with high-performance liquid chromatography.
Results:
Ischemia resulted in a prompt increase in norepinephrine concentrations in the striatum in all groups. However, there were no significant differences in norepinephrine concentrations in the striatum between the three groups at any period.
Conclusions:
Our results indicate that mivazerol did not attenuate ischemia-induced increase in striatal norepinephrine concentration. This suggests that the possible neuroprotective property of mivazerol is not related to inhibition of norepinephrine release in the brain.
Insights
Mivazerol, an alpha(2)-agonist, did not reduce the increase in striatal norepinephrine after forebrain ischemia in rats. This suggests its potential neuroprotective effects are not linked to inhibiting norepinephrine release in the brain.
Area of Science:
- Neuroscience
- Pharmacology
- Ischemia Research
Background:
- Mivazerol, an alpha(2)-agonist, may offer neuroprotection against transient forebrain ischemia.
- Previous studies suggested a potential neuroprotective role for mivazerol.
Purpose of the Study:
- To investigate if mivazerol attenuates the ischemia-induced increase in striatal norepinephrine concentration.
- To explore the mechanism of mivazerol's potential neuroprotective effects.
Main Methods:
- Male Sprague-Dawley rats underwent transient forebrain ischemia.
- Rats received saline, mivazerol 20 µg/kg, or 40 µg/kg.
- Striatal norepinephrine was measured using in vivo microdialysis and HPLC.
Main Results:
- Forebrain ischemia increased striatal norepinephrine in all experimental groups.
- No significant differences in norepinephrine levels were observed between control and mivazerol-treated groups.
Conclusions:
- Mivazerol did not attenuate the ischemia-induced increase in striatal norepinephrine.
- The neuroprotective property of mivazerol is likely not mediated by the inhibition of norepinephrine release.
