Targeted Occlusion to Surface and Deep Vessels in Neocortex Via Linear and Nonlinear Optical Absorption

We discuss two complementary methods for the study of cerebral blood flow and brain function in response to the occlusion of individual, targeted blood vessels. These bear on the study of microstroke and vascular dysfunction in cortex. One method makes use of linear optical absorption by a photosensitizer, transiently circulated in the blood stream, to induce an occlusion in a surface or near-surface vessel. The second method makes use of nonlinear optical interactions, without the need to introduce an exogenous absorber, to induce an occlusion in a subsurface microvessel. A feature of both methods is that the dynamics of blood flow and functional aspects of the vasculature and underlying neurons in the neighborhood of the occluded vessel may be monitored before, during, and after the occlusion. We present details of both methods and associated surgical procedures, along with example data from published studies.

[1]  J. Sharkey Perivascular Microapplication of Endothelin-1: A New Model of Focal Cerebral Ischaemia in the Rat , 1993, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[2]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[3]  D. Graham,et al.  Endothelin-1-Induced Reductions in Cerebral Blood Flow: Dose Dependency, Time Course, and Neuropathological Consequences , 1993, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[4]  F. Helmchen,et al.  Resting Microglial Cells Are Highly Dynamic Surveillants of Brain Parenchyma in Vivo , 2005, Science.

[5]  S. Carmichael,et al.  Tissue Microenvironments within Functional Cortical Subdivisions Adjacent to Focal Stroke , 2003, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[6]  C G Markgraf,et al.  Comparative Histopathologic Consequences of Photothrombotic Occlusion of the Distal Middle Cerebral Artery in Sprague‐Dawley and Wistar Rats , 1993, Stroke.

[7]  A. Tamura,et al.  Correlation Between rCBF and Histological Changes Following Temporary Middle Cerebral Artery Occlusion , 1980, Stroke.

[8]  Rafael Yuste,et al.  A custom-made two-photon microscope and deconvolution system , 2000, Pflügers Archiv.

[9]  A. Buchan,et al.  A New Model of Temporary Focal Neocortical Ischemia in the Rat , 1992, Stroke.

[10]  Ulrich Dirnagl,et al.  In‐vivo confocal scanning laser microscopy of the cerebral microcirculation , 1992, Journal of microscopy.

[11]  C. E. Short,et al.  Principles & practice of veterinary anesthesia , 1987 .

[12]  D. Kleinfeld,et al.  In vivo dendritic calcium dynamics in neocortical pyramidal neurons , 1997, Nature.

[13]  Timothy H Murphy,et al.  Rapid Reversible Changes in Dendritic Spine Structure In Vivo Gated by the Degree of Ischemia , 2005, The Journal of Neuroscience.

[14]  C. Iadecola Neurovascular regulation in the normal brain and in Alzheimer's disease , 2004, Nature Reviews Neuroscience.

[15]  S. Takeo,et al.  Sustained Decrease in Brain Regional Blood Flow After Microsphere Embolism in Rats , 1993, Stroke.

[16]  D. Kleinfeld,et al.  Two-Photon Imaging of Cortical Surface Microvessels Reveals a Robust Redistribution in Blood Flow after Vascular Occlusion , 2006, PLoS biology.

[17]  G. Paxinos The Rat nervous system , 1985 .

[18]  D. Kleinfeld,et al.  Distributed representation of vibrissa movement in the upper layers of somatosensory cortex revealed with voltage‐sensitive dyes , 1996, The Journal of comparative neurology.

[19]  E. Hogan,et al.  A model of focal ischemic stroke in the rat: reproducible extensive cortical infarction. , 1986, Stroke.

[20]  Tibo Gerriets,et al.  The macrosphere model Evaluation of a new stroke model for permanent middle cerebral artery occlusion in rats , 2003, Journal of Neuroscience Methods.

[21]  A. Foundas,et al.  The Cerebral Vascular System , 2008 .

[22]  David Kleinfeld,et al.  Principles, Design,and Construction of a Two-Photon Laser-Scanning Microscopefor In Vitro and In Vivo Brain Imaging , 2002 .

[23]  R. Frostig In Vivo Optical Imaging of Brain Function , 2002 .

[24]  D. Kleinfeld,et al.  Targeted insult to individual subsurface cortical blood vessels using ultrashort laser pulses : Three models of stroke , 2005 .

[25]  David Kleinfeld,et al.  Penetrating arterioles are a bottleneck in the perfusion of neocortex , 2007, Proceedings of the National Academy of Sciences.

[26]  K. Fuxe,et al.  Endothelin‐1 induced lesions of the frontoparietal cortex of the rat. A possible model of focal cortical ischemia , 1997, Neuroreport.

[27]  David Kleinfeld,et al.  Large two-photon absorptivity of hemoglobin in the infrared range of 780-880 nm. , 2007, The Journal of chemical physics.

[28]  T A Woolsey,et al.  Ministrokes in rat barrel cortex. , 1995, Stroke.

[29]  W. Denk,et al.  Deep tissue two-photon microscopy , 2005, Nature Methods.

[30]  T. Murphy,et al.  Imaging the Impact of Cortical Microcirculation on Synaptic Structure and Sensory-Evoked Hemodynamic Responses In Vivo , 2007, PLoS biology.

[31]  Rafael Yuste,et al.  Imaging neurons : a laboratory manual , 1999 .

[32]  Albert van der Zwan,et al.  Anatomy and Functionality of Leptomeningeal Anastomoses: A Review , 2003, Stroke.

[33]  M. Chopp,et al.  A New Rat Model of Thrombotic Focal Cerebral Ischemia , 1997, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[34]  K. Hossmann,et al.  The effect of mild microembolic injury on the energy metabolism of the cat brain , 2004, Journal of Neurology.

[35]  D. Kleinfeld,et al.  Targeted insult to subsurface cortical blood vessels using ultrashort laser pulses: three models of stroke , 2006, Nature Methods.

[36]  D. Kleinfeld,et al.  Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex. , 1998, Proceedings of the National Academy of Sciences of the United States of America.