The smallest stroke: occlusion of one penetrating vessel leads to infarction and a cognitive deficit (original) (raw)

References

1. Gorelick, P.B. et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 42, 2672–2713 (2011).
   Article PubMed PubMed Central Google Scholar
2. Brundel, M., de Bresser, J., van Dillen, J.J., Kappelle, L.J. & Biessels, G.J. Cerebral microinfarcts: a systematic review of neuropathological studies. J. Cereb. Blood Flow Metab. 32, 425–436 (2012).
   Article PubMed PubMed Central Google Scholar
3. Smith, E.E., Schneider, J.A., Wardlaw, J.M. & Greenberg, S.M. Cerebral microinfarcts: the invisible lesions. Lancet Neurol. 11, 272–282 (2012).
   Article PubMed PubMed Central Google Scholar
4. Vinters, H.V. et al. Neuropathologic substrates of ischemic vascular dementia. J. Neuropathol. Exp. Neurol. 59, 931–945 (2000).
   Article CAS PubMed Google Scholar
5. Kövari, E. et al. Cortical microinfarcts and demyelination affect cognition in cases at high risk for dementia. Neurology 68, 927–931 (2007).
   Article PubMed Google Scholar
6. Arvanitakis, Z., Leurgans, S.E., Barnes, L.L., Bennett, D.A. & Schneider, J.A. Microinfarct pathology, dementia and cognitive systems. Stroke 42, 722–727 (2011).
   Article PubMed PubMed Central Google Scholar
7. Jouvent, E. et al. Intracortical infarcts in small vessel disease: a combined 7-T postmortem MRI and neuropathological case study in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopthy. Stroke 42, 27–30 (2011).
   Article Google Scholar
8. Blinder, P., Shih, A.Y., Rafie, C.A. & Kleinfeld, D. Topological basis for the robust distribution of blood to rodent neocortex. Proc. Natl. Acad. Sci. USA 107, 12670–12675 (2010).
   Article CAS PubMed PubMed Central Google Scholar
9. Lauwers, F., Cassot, F., Lauwers-Cances, V., Puwanarajah, P. & Duvernoy, H. Morphometry of the human cerebral cortex microcirculation: general characteristics and space-related profiles. Neuroimage 39, 936–948 (2008).
   Article PubMed Google Scholar
10. Bär, T. The vascular system of the cerebral cortex. Adv. Anat. Embryol. Cell Biol. 59, 1–62 (1980).
    Article Google Scholar
11. Nishimura, N., Schaffer, C.B., Friedman, B., Lyden, P.D. & Kleinfeld, D. Penetrating arterioles are a bottleneck in the perfusion of neocortex. Proc. Natl. Acad. Sci. USA 104, 365–370 (2007).
    Article CAS PubMed Google Scholar
12. Nguyen, J., Nishimura, N., Fetcho, R.N., Iadecola, C. & Schaffer, C.B. Occlusion of cortical ascending venules causes blood flow decreases, reversals in flow direction, and vessel dilation in upstream capillaries. J. Cereb. Blood Flow Metab. 31, 2243–2254 (2011).
    Article PubMed PubMed Central Google Scholar
13. Drew, P.J. et al. Chronic optical access through a polished and reinforced thinned skull. Nat. Methods 7, 981–984 (2010).
    Article CAS PubMed PubMed Central Google Scholar
14. Sofroniew, M.V. & Vinters, H.V. Astrocytes: biology and pathology. Acta Neuropathol. 119, 7–35 (2010).
    Article PubMed Google Scholar
15. Tsai, P.S. et al. Correlations of neuronal and microvascular densities in murine cortex revealed by direct counting and colocalization of cell nuclei and microvessels. J. Neurosci. 29, 14553–14570 (2009).
    Article CAS PubMed PubMed Central Google Scholar
16. Weber, B., Keller, A.L., Reichold, J. & Logothetis, N.K. The microvascular system of the striate and extrastriate visual cortex of the macaque. Cereb. Cortex 18, 2318–2330 (2008).
    Article PubMed Google Scholar
17. Svoboda, K., Denk, W., Kleinfeld, D. & Tank, D.W. In vivo dendritic calcium dynamics in neocortical pyramidal neurons. Nature 385, 161–165 (1997).
    Article CAS PubMed Google Scholar
18. Kleinfeld, D., Mitra, P.P., Helmchen, F. & Denk, W. Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex. Proc. Natl. Acad. Sci. USA 95, 15741–15746 (1998).
    Article CAS PubMed PubMed Central Google Scholar
19. Shih, A.Y. et al. Active dilation of penetrating arterioles restores red blood cell flux to penumbral neocortex after focal stroke. J. Cereb. Blood Flow Metab. 29, 738–751 (2009).
    Article PubMed Google Scholar
20. Shih, A.Y. et al. Two-photon microscopy as a tool to study blood flow and neurovascular coupling in the rodent brain. J. Cereb. Blood Flow Metab. 32, 1277–1309 (2012).
    Article CAS PubMed PubMed Central Google Scholar
21. Schaffer, C.B. et al. Two-photon imaging of cortical surface microvessels reveals a robust redistribution in blood flow after vascular occlusion. PLoS Biol. 4, e22 (2006).
    Article PubMed PubMed Central CAS Google Scholar
22. Nishimura, N. et al. Targeted insult to individual subsurface cortical blood vessels using ultrashort laser pulses: three models of stroke. Nat. Methods 3, 99–108 (2006).
    Article CAS PubMed Google Scholar
23. Stosiek, C., Garaschuk, O., Holthoff, K. & Konnerth, A. In vivo two-photon calcium imaging of neuronal networks. Proc. Natl. Acad. Sci. USA 100, 7319–7324 (2003).
    Article CAS PubMed PubMed Central Google Scholar
24. Chen, B. et al. Severe blood brain barrier disruption and surrounding tissue injury. Stroke 40, 666–674 (2009).
    CAS Google Scholar
25. Calabrese, V., Mancuso, C., Calvani, M., Rizzarelli, E. & Butterfield, D.A. Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity. Nat. Rev. Neurosci. 8, 766–775 (2007).
    Article CAS PubMed Google Scholar
26. Friedman, B. et al. Acute vascular disruption and Aquaporin 4 loss after stroke. Stroke 40, 2182–2190 (2009).
    Article PubMed PubMed Central Google Scholar
27. Unal Cevik, I. & Dalkara, T. Intravenously administered propidium iodide labels necrotic cells in the intact mouse brain after injury. Cell Death Differ. 10, 928–929 (2003).
    Article CAS PubMed Google Scholar
28. Soontornniyomkij, V. et al. Cerebral microinfarcts associated with severe cerebral beta-amyloid angiopathy. Brain Pathol. 20, 459–467 (2010).
    Article PubMed Google Scholar
29. Siesjô, B.K. & Bengtsson, F. Calcium fluxes, calcium antagonists and calcium-related pathology in brain ischemia, hypoglycemia, and spreading depression: a unifying hypothesis. J. Cereb. Blood Flow Metab. 9, 127–140 (1989).
    Article PubMed Google Scholar
30. Murphy, T.H., Li, P., Betts, K. & Liu, R. Two-photon imaging of stroke onset in vivo reveals that NMDA receptor–independent ischemic depolarization is the major cause of rapid reversible damage to dendrites and spines. J. Neurosci. 28, 1756–1772 (2008).
    Article CAS PubMed PubMed Central Google Scholar
31. Orgogozo, J.M., Rigaud, A.S., Stoffler, A., Mobius, H.J. & Forette, F. Efficacy and safety of Memantine in patients with mild to moderate vascular dementia. Stroke 33, 1834–1839 (2002).
    Article CAS PubMed Google Scholar
32. Olivares, D. et al. N-Methyl D-Aspartate (NMDA) receptor antagonists and memantine treatment for Alzheimer's disease, vascular dementia and Parkinson's disease. Curr. Alzheimer Res. 9, 746–758 (2012).
    Article CAS PubMed PubMed Central Google Scholar
33. Woolsey, T.A. & Van Der Loos, H. The structural organization of layer IV in the somatosensory region (SI) of mouse cerebral cortex. Brain Res. 17, 205–242 (1970).
    Article CAS PubMed Google Scholar
34. Kleinfeld, D. & Deschênes, M. Neuronal basis for object location in the vibrissa scanning sensorimotor system. Neuron 72, 455–468 (2011).
    Article CAS PubMed PubMed Central Google Scholar
35. Hutson, K.A. & Masterton, R.B. The sensory contribution of a single vibrissa's cortical barrel. J. Neurophysiol. 56, 1196–1223 (1986).
    Article CAS PubMed Google Scholar
36. Masino, S.A., Kwon, M.C., Dory, Y. & Frostig., R.D. Characterization of functional organization within rat barrel cortex using intrinsic signal optical imaging through a thinned skull. Proc. Natl. Acad. Sci. USA 90, 9998–10002 (1993).
    Article CAS PubMed PubMed Central Google Scholar
37. Armstrong-James, M., Fox, K. & Das-Gupta, A. Flow of excitability within barrel cortex on striking a single vibrissa. J. Neurophysiol. 68, 1345–1358 (1992).
    Article CAS PubMed Google Scholar
38. Lashley, K.S. Mass action in cerebral function. Science 73, 245–254 (1931).
    Article CAS PubMed Google Scholar
39. Reisberg, B. et al. Memantine in moderate-to-severe Alzheimer's disease. N. Engl. J. Med. 348, 1333–1341 (2003).
    Article CAS PubMed Google Scholar
40. Wilcock, G.K. Memantine for the treatment of dementia. Lancet Neurol. 2, 503–505 (2003).
    Article CAS PubMed Google Scholar
41. Woolsey, T.A. et al. Neuronal units linked to microvascular modules in cerebral cortex: response elements for imaging the brain. Cereb. Cortex 6, 647–660 (1996).
    Article CAS PubMed Google Scholar
42. Cassot, F. et al. Branching patterns for arterioles and venules of the human cerebral cortex. Brain Res. 1313, 62–78 (2010).
    Article CAS PubMed Google Scholar
43. Villringer, A., Mehraein, S. & Einhäupl, K.M. Pathophysiological aspects of cerebral sinus venous thrombosis (SVT). J. Neuroradiol. 21, 72–80 (1994).
    CAS PubMed Google Scholar
44. Brown, W.R. & Thore, C.R. Cerebral microvascular pathology in aging and neurodegeneration. Neuropathol. Appl. Neurobiol. 37, 56–74 (2011).
    Article CAS PubMed PubMed Central Google Scholar
45. Zhang, S. & Murphy, T.H. Imaging the impact of cortical microcirculation on synaptic structure and sensory-evoked hemodynamic responses in vivo. PLoS Biol. 5, e119 (2007).
    Article PubMed PubMed Central CAS Google Scholar
46. Troncoso, E. et al. Recovery of evoked potentials, metabolic activity and behavior in a mouse model of somatosensory cortex lesion: role of the neural cell adhesion molecule (NCAM). Cereb. Cortex 14, 332–341 (2004).
    Article CAS PubMed Google Scholar
47. Carmichael, S.T. Plasticity of cortical projections after stroke. Neuroscienist 9, 64–75 (2003).
    Article Google Scholar
48. Mohajerani, M.H., Aminoltejari, K. & Murphy, T.H. Targeted mini-strokes produce changes in interhemispheric sensory signal processing that are indicative of disinhibition within minutes. Proc. Natl. Acad. Sci. USA 108, E183–E191 (2011).
    Article PubMed PubMed Central Google Scholar
49. Rosidi, N.L. et al. Cortical microhemorrhages cause local inflammation but do not trigger widespread dendrite degeneration. PLoS ONE 6, e26612 (2011).
    Article CAS PubMed PubMed Central Google Scholar
50. Nishimura, N., Rosidi, N.L., Iadecola, C. & Schaffer, C.B. Limitations of collateral flow after occlusion of a single cortical penetrating arteriole. J. Cereb. Blood Flow Metab. 30, 1914–1927 (2010).
    Article PubMed PubMed Central Google Scholar
51. Frostig, R.D., Lieke, E.E., Ts'o, D.Y. & Grinvald, A. Cortical functional architecture and local coupling between neuronal activity and the microcirculation revealed by in vivo high-resolution optical imaging of intrinsic signals. Proc. Natl. Acad. Sci. USA 87, 6082–6086 (1990).
    Article CAS PubMed PubMed Central Google Scholar
52. Kleinfeld, D. & Delaney, K.R. Distributed representation of vibrissa movement in the upper layers of somatosensory cortex revealed with voltage sensitive dyes. J. Comp. Neurol. 375, 89–108 (1996).
    Article CAS PubMed Google Scholar
53. Tsai, P.S. & Kleinfeld, D. In vivo two-photon laser scanning microscopy with concurrent plasma-mediated ablation: principles and hardware realization. in Methods for In Vivo Optical Imaging 2nd edn. (ed. Frostig, R.D.) 59–115 (CRC Press, 2009).
54. Valmianski, I. et al. Automatic identification of fluorescently labeled brain cells for rapid functional imaging. J. Neurophysiol. 104, 1803–1811 (2010).
    Article PubMed PubMed Central Google Scholar
55. Driscoll, J.D., Shih, A.Y., Drew, P.J., Cauwenberghs, G. & Kleinfeld, D. Two-photon imaging of blood flow in cortex. in Imaging in Neuroscience: A Laboratory Manual (eds. Helmchen, F., Konnerth, A. & Yuste, R.) 927–938 (Cold Spring Harbor Laboratory Press, New York, 2011).
56. Shih, A.Y. et al. Optically induced occlusion of single blood vessels in neocortex. in Imaging in Neuroscience: A Laboratory Manual (eds. Helmchen, F., Konnerth, A. & Yuste, R.) 939–948 (Cold Spring Harbor Laboratory Press, New York, 2011).
57. Nguyen, Q.-T., Dolnick, E.M., Driscoll, J. & Kleinfeld, D. MPScope 2.0: A computer system for two-photon laser scanning microscopy with concurrent plasma-mediated ablation and electrophysiology. in Methods for In Vivo Optical Imaging 2nd edn. (ed. Frostig, R.D.) 117–142 (CRC Press, 2009).
58. Nimmerjahn, A., Kirchhoff, F., Kerr, J.N. & Helmchen, F. Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo. Nat. Methods 1, 31–37 (2004).
    Article CAS PubMed Google Scholar
59. Mehta, S.B., Whitmer, D., Figueroa, R., Williams, B.A. & Kleinfeld, D. Active spatial perception in the vibrissa scanning sensorimotor system. PLoS Biol. 5, 309–322 (2007).
    Article CAS Google Scholar
60. Paxinos, G. & Watson, C. The Rat Brain in Stereotaxic Coordinates (Academic Press, San Diego, 1986).

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