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Updated: Jun 3, 2026
A Murine Model of Ischemic Retinal Injury Induced by Transient Bilateral Common Carotid Artery Occlusion
Published on: November 12, 2020
Rat pial microvascular responses to melatonin during bilateral common carotid artery occlusion and reperfusion
Dominga Lapi1, Sabrina Vagnani, Emilio Cardaci
1Department of Neuroscience, Federico II University Medical School, Naples, Italy. d.lapi@dfb.unipi.it
Abstract:
The present study assessed the in vivo rat pial microvascular responses induced by melatonin during brain hypoperfusion and reperfusion (RE) injury. Pial microcirculation of male Wistar rats was visualized by fluorescence microscopy through a closed cranial window. Hypoperfusion was induced by bilateral common carotid artery occlusion (BCCAO, 30 min); thereafter, pial microcirculation was observed for 60 min. Arteriolar diameter, permeability increase, leukocyte adhesion to venular walls, perfused capillary length (PCL), and capillary red blood cell velocity (V(RBC) ) were investigated by computerized methods. Melatonin (0.5, 1, 2 mg/kg b.w.) was intravenously administered 10 min before BCCAO and at the beginning of RE. Pial arterioles were classified in five orders according to diameter, length, and branchings. In control group, BCCAO caused decrease in order 2 arteriole diameter (by 17.5 ± 3.0% of baseline) that was reduced by 11.8 ± 1.2% of baseline at the end of RE, accompanied by marked leakage and leukocyte adhesion. PCL and capillary V(RBC) decreased. At the end of BCCAO, melatonin highest dosage caused order 2 arteriole diameter reduction by 4.6 ± 2.0% of baseline. At RE, melatonin at the lower dosages caused different arteriolar responses. The highest dosage caused dilation in order 2 arteriole by 8.0 ± 1.5% of baseline, preventing leakage and leukocyte adhesion, while PCL and V(RBC) increased. Luzindole (4 mg/kg b.w.) prior to melatonin caused order 2 arteriole constriction by 12.0 ± 1.5% of baseline at RE, while leakage, leukocyte adhesion, PCL and V(RBC) were not affected. Prazosin (1 mg/kg b.w.) prior to melatonin did not significantly change melatonin's effects. In conclusion, melatonin caused different responses during hypoperfusion and RE, modulating pial arteriolar tone likely by MT1 and MT2 melatonin receptors while preventing blood-brain barrier changes through its free radical scavenging action.
Insights
Melatonin protects the brain during hypoperfusion and reperfusion injury by modulating pial arteriolar tone and preventing blood-brain barrier damage. This neuroprotective effect is mediated through melatonin receptors and free radical scavenging.
Area of Science:
- Neuroscience
- Pharmacology
- Cerebrovascular Physiology
Background:
- Brain hypoperfusion and reperfusion (RE) injury can lead to significant neurological damage.
- Melatonin, a hormone with antioxidant properties, has shown potential neuroprotective effects.
- Understanding melatonin's impact on pial microcirculation during these injury phases is crucial.
Purpose of the Study:
- To investigate the in vivo effects of melatonin on rat pial microvascular responses during hypoperfusion and RE injury.
- To elucidate the mechanisms underlying melatonin's potential neuroprotective actions, including receptor involvement and antioxidant activity.
Main Methods:
- Male Wistar rats underwent bilateral common carotid artery occlusion (BCCAO) to induce hypoperfusion, followed by a reperfusion period.
- Pial microcirculation was visualized using fluorescence microscopy, assessing arteriolar diameter, permeability, leukocyte adhesion, capillary length, and red blood cell velocity.
- Melatonin was administered intravenously before BCCAO and at the start of RE; receptor antagonists (luzindole, prazosin) were used to probe mechanisms.
Main Results:
- BCCAO induced significant arteriolar constriction, increased permeability, leukocyte adhesion, and reduced capillary perfusion.
- Melatonin, particularly at higher doses, attenuated hypoperfusion-induced arteriolar constriction and prevented RE-induced damage.
- Melatonin administration increased arteriolar dilation, reduced leakage and leukocyte adhesion, and improved capillary perfusion during RE; luzindole blocked these effects.
Conclusions:
- Melatonin exhibits differential effects during hypoperfusion and RE, modulating pial arteriolar tone.
- The neuroprotective actions of melatonin are likely mediated via MT1 and MT2 melatonin receptors.
- Melatonin prevents blood-brain barrier disruption through its potent free radical scavenging activity.
