Targeted insult to subsurface cortical blood vessels using ultrashort laser pulses: three models of stroke.
We present a method to produce vascular disruptions within rat brain parenchyma that targets single microvessels. We used two-photon microscopy to image vascular architecture, to select a vessel for injury and to measure blood-flow dynamics. We irradiated the vessel with high-fluence, ultrashort laser pulses and achieved three forms of vascular insult. (i) Vessel rupture was induced at the highest optical energies; this provides a model for hemorrhage. (ii) Extravasation of blood components was induced near the lowest energies and was accompanied by maintained flow in the target vessel. (iii) An intravascular clot evolved when an extravasated vessel was further irradiated. Such clots dramatically impaired blood flow in downstream vessels, in which speeds dropped to as low as approximately 10% of baseline values. This demonstrates that a single blockage to a microvessel can lead to local cortical ischemia. Lastly, we show that hemodilution leads to a restoration of flow in secondary downstream vessels.
Nishimura
Nozomi
N
Department of Physics, University of California at San Diego, La Jolla, California 92093, USA.
Schaffer
Chris B
CB
Friedman
Beth
B
Tsai
Philbert S
PS
Lyden
Patrick D
PD
Kleinfeld
David
D
D000818:Animals; D001777:Blood Coagulation; D001783:Blood Flow Velocity / Q000187:drug effects / Q000528:radiation effects; D001929:Brain Edema / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology; D002199:Capillary Permeability / Q000528:radiation effects; D002540:Cerebral Cortex / Q000098:blood supply* / Q000473:pathology / Q000528:radiation effects; D003911:Dextrans / Q000097:blood; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000166:cytology; D005337:Fibrin / Q000032:analysis; D005452:Fluoresceins; D006438:Hemodilution; D006470:Hemorrhage / Q000473:pathology; D006493:Heparin / Q000494:pharmacology; D002534:Hypoxia, Brain / Q000473:pathology; D007834:Lasers / Q000009:adverse effects; D008027:Light / Q000009:adverse effects; D008297:Male; D008833:Microcirculation / Q000528:radiation effects; D018613:Microscopy, Confocal / Q000379:methods; D008869:Microtubule-Associated Proteins / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects / Q000528:radiation effects; D012421:Rupture / Q000473:pathology; D012965:Sodium Chloride / Q000494:pharmacology; D020521:Stroke / Q000473:pathology*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology; D014746:Vimentin / Q000032:analysis
D003911:Dextrans; D005452:Fluoresceins; D008869:Microtubule-Associated Proteins; D014746:Vimentin; C052526:fluorescein-dextran; D012965:Sodium Chloride; D005337:Fibrin; D006493:Heparin; D010959:Tissue Plasminogen Activator