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Non-invasive Imaging and Analysis of Cerebral Ischemia in Living Rats Using Positron Emission Tomography with 18F-FDG
Published on: December 28, 2014
Dynamic spatio-temporal imaging of early reflow in a neonatal rat stroke model
Pierre-Louis Leger1, Philippe Bonnin, Pierre Lacombe
1Sorbonne Paris Cité, INSERM U676, Univ Paris Diderot, Paris, France.
Insights
This study reveals how blood flow recovers in immature rat brains after arterial occlusion. Early reflow shows a caudorostral gradient, with collateral pathways supporting perfusion despite mitochondrial impairment.
Area of Science:
- Neuroscience
- Cerebrovascular Physiology
- Pediatric Neurology
Background:
- Understanding cerebral blood flow dynamics is crucial for managing ischemic events in developing brains.
- Arterial occlusion in immature brains can lead to complex reperfusion patterns.
- The role of collateral circulation in early reflow is not fully elucidated.
Purpose of the Study:
- To investigate blood flow changes in large arteries and microvessels during the initial 15 minutes of reflow following arterial occlusion in a P7 rat model.
- To characterize the spatiotemporal patterns of cerebral reperfusion and their impact on tissue perfusion and energy metabolism.
Main Methods:
- Ultrasound imaging with Doppler recordings in internal carotid arteries (ICAs) and basilar trunk.
- Laser speckle Doppler monitoring for relative cerebral blood flow (rCBF) measurements.
- [(14)C]-iodoantipyrine autoradiography for tissue perfusion assessment.
- Mitochondrial oxygen consumption assays to evaluate cerebral energy metabolism.
Main Results:
- Gradual increases in mean blood flow velocities were observed in ICAs during early reflow.
- Ischemia showed residual perfusion in the middle cerebral artery (MCA) territory, while caudal regions remained perfused.
- Reflow demonstrated a caudorostral propagation of reperfusion via anastomoses, with reduced perfusion in the MCA territory.
- Autoradiography confirmed a caudorostral gradient and persistent perfusion in ventral/medial regions.
- Mitochondrial respiration impairment was noted in the ipsilateral cortex.
Conclusions:
- The immature rat brain utilizes a primary collateral pathway through the circle of Willis for immediate diversion of blood flow to ischemic areas.
- Secondary, efficient cortical anastomoses contribute to reperfusion in the immature brain.
- These findings highlight the complex interplay of collateral circulation and metabolic compromise during early cerebral reflow in young animals.
Abstract:
The aim of the study was to better understand blood-flow changes in large arteries and microvessels during the first 15 minutes of reflow in a P7 rat model of arterial occlusion. Blood-flow changes were monitored by using ultrasound imaging with sequential Doppler recordings in internal carotid arteries (ICAs) and basilar trunk. Relative cerebral blood flow (rCBF) changes were obtained by using laser speckle Doppler monitoring. Tissue perfusion was measured with [(14)C]-iodoantipyrine autoradiography. Cerebral energy metabolism was evaluated by mitochondrial oxygen consumption. Gradual increase in mean blood-flow velocities illustrated a gradual perfusion during early reflow in both ICAs. On ischemia, the middle cerebral artery (MCA) territory presented a residual perfusion, whereas the caudal territory remained normally perfused. On reflow, speckle images showed a caudorostral propagation of reperfusion through anastomotic connections, and a reduced perfusion in the MCA territory. Autoradiography highlighted the caudorostral gradient, and persistent perfusion in ventral and medial regions. These blood-flow changes were accompanied by mitochondrial respiration impairment in the ipsilateral cortex. Collectively, these data indicate the presence of a primary collateral pathway through the circle of Willis, providing an immediate diversion of blood flow toward ischemic regions, and secondary efficient cortical anastomoses in the immature rat brain.
