Laser Doppler flowmetry in non-human primate stroke studies: model refinement for pre-clinical development of cerebroprotective strategies.

Abstract

BACKGROUND:

Safety, feasibility, and efficacy trials in non-human primate stroke models are essential to the evaluation of experimental therapies and their translation to humans. Although Laser Doppler Flowmetry has been successfully employed in rodent stroke to continuously monitor cerebral blood flow, it has not been applied in primate studies. This investigation examined the utility of Laser Doppler Flowmetry in refining an existing baboon model of cerebral ischemia/reperfusion.

METHOD:

Continuous Laser Doppler Flowmetry monitoring was used, in non-human primates, to document local cerebral blood flow before, during, and after middle cerebral artery territory occlusion. In each baboon (n = 7) a single Doppler probe was placed into the left frontal cortex through a precoronal burr hole. Correlations between Laser Doppler Flowmetry values and latencies to Motor Evoked Potential dropout were compared using a linear regression model.

FINDINGS:

Placement of the Laser Doppler probe was easily accomplished in all animals. Laser Doppler Flowmetry tracings accurately documented blood flow changes that occurred with each technical manipulation during the procedure. Laser Doppler confirmed decreased perfusion that coincided both regionally and temporally with vessel occlusion. Depth of ischemia as measured by Laser Doppler Flowmetry was associated with Motor Evoked Potential dropout latencies for individual animals.

CONCLUSIONS:

Continuous, single probe Laser Doppler Flowmetry is a reliable method of documenting perfusion changes following middle cerebral artery territory occlusion in a baboon model of reperfused stroke. This advanced intraoperative monitoring technique may lead to more accurate evaluation of acute stroke therapies in pre-clinical trials.

• Authors: C J Winfree, W J Mack, D Hoh, R King, A F Ducruet, A L D'Ambrosio, M E Sughrue, J McKinnell, E S Connolly Jr
• Journal: Acta neurochirurgica (Acta Neurochir (Wien)) Vol. 145 Issue 12 Pg. 1105-10; discussion 1110 (Dec 2003) ISSN: 0001-6268 [Print] Austria
• PMID: 14663568 (Publication Type: Journal Article)

Chemical References

• Neuroprotective Agents

Topics

• Animals
• Cerebral Cortex (blood supply)
• Disease Models, Animal
• Dominance, Cerebral (physiology)
• Drug Evaluation, Preclinical
• Electric Stimulation
• Electrodes, Implanted
• Evoked Potentials, Motor (physiology)
• Frontal Lobe (blood supply)
• Infarction, Middle Cerebral Artery (physiopathology)
• Laser-Doppler Flowmetry
• Male
• Motor Cortex (blood supply)
• Muscle, Skeletal (innervation)
• Neuroprotective Agents (pharmacology)
• Papio
• Reaction Time (physiology)
• Reperfusion Injury (physiopathology)