Abstract

We report here on the development of a method for inducing a stroke in a specific location within a mouse brain through the use of an optical fiber. By capturing the emitted fluorescence signal generated using the same fiber it is possible to monitor photochemical changes within the brain in real-time, and directly measure the concentration of the stroke-inducing dye, Rose Bengal, at the infarct site. This technique reduces the requirement for post-operative histology to determine if a stroke has successfully been induced within the animal, and therefore opens up the opportunity to explore the recovery of the brain after the stroke event.

© 2014 Optical Society of America

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References

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  1. S. Senes, How We Manage Stroke in Australia (Australian Institute of Health and Welfare, 2006).
  2. C. Mathers, D. M. Fat, and J. Boerma, The Global Burden of Disease: 2004 update (World Health Organization, 2008).
  3. U. Dirnagl, C. Iadecola, and M. A. Moskowitz, “Pathobiology of ischaemic stroke: an integrated view,” Trends Neurosci. 22(9), 391–397 (1999).
    [Crossref] [PubMed]
  4. U. Dirnagl, “Rodent models of stroke,”, 7, (Springer, New York, 2010).
  5. B. D. Watson, W. D. Dietrich, R. Busto, M. S. Wachtel, and M. D. Ginsberg, “Induction of reproducible brain infarction by photochemically initiated thrombosis,” Ann. Neurol. 17(5), 497–504 (1985).
    [Crossref] [PubMed]
  6. J. D. Lozano, D. P. Abulafia, G. H. Danton, B. D. Watson, and W. D. Dietrich, “Characterization of a thromboembolic photochemical model of repeated stroke in mice,” J. Neurosci. Methods 162(1-2), 244–254 (2007).
    [Crossref] [PubMed]
  7. H. Nakase, A. Heimann, and O. Kempski, “Local cerebral blood flow in a rat cortical vein occlusion model,” J. Cereb. Blood Flow Metab. 16(4), 720–728 (1996).
    [Crossref] [PubMed]
  8. H. Nakase, K. Nagata, H. Otsuka, T. Sakaki, and O. Kempski, “Local cerebral blood flow autoregulation following “asymptomatic” cerebral venous occlusion in the rat,” J. Neurosurg. 89(1), 118–124 (1998).
    [Crossref] [PubMed]
  9. T. Kuroiwa, G. Xi, Y. Hua, T. N. Nagaraja, J. D. Fenstermacher, and R. F. Keep, “Development of a rat model of photothrombotic ischemia and infarction within the caudoputamen,” Stroke 40(1), 248–253 (2009).
    [Crossref] [PubMed]
  10. T. Kuroiwa and R. F. Keep, “Photothrombotic infarction of caudate nucleus and parietal cortex,” Neuromethods 62, 183–191 (2011).
    [Crossref]
  11. A. M. I. Barth and I. Mody, “Changes in hippocampal neuronal activity during and after unilateral selective hippocampal ischemia in vivo,” J. Neurosci. 31(3), 851–860 (2011).
    [Crossref] [PubMed]
  12. X.-D. Wang and O. S. Wolfbeis, “Fiber-optic chemical sensors and biosensors (2008-2012),” Anal. Chem. 85(2), 487–508 (2013).
    [Crossref] [PubMed]
  13. X.-D. Wang, O. S. Wolfbeis, and R. J. Meier, “Luminescent probes and sensors for temperature,” Chem. Soc. Rev. 42(19), 7834–7869 (2013).
    [Crossref] [PubMed]
  14. P. R. Hof, W. G. Young, F. E. Bloom, P. V. Belichenko, and M. R. Celio, Comparative Cytoarchitectonic Atlas of the C57BL/6 and 129/Sv Mouse Brains (Elsevier, Amsterdam, 2000).
  15. C. A. Paul, B. Beltz and J. Berger-Sweeney, “The nissl stain: a stain for cell bodies in brain sections,” CSH protocols 2008, pdb. prot4805-pdb. prot4805 (2007).

2013 (2)

X.-D. Wang and O. S. Wolfbeis, “Fiber-optic chemical sensors and biosensors (2008-2012),” Anal. Chem. 85(2), 487–508 (2013).
[Crossref] [PubMed]

X.-D. Wang, O. S. Wolfbeis, and R. J. Meier, “Luminescent probes and sensors for temperature,” Chem. Soc. Rev. 42(19), 7834–7869 (2013).
[Crossref] [PubMed]

2011 (2)

T. Kuroiwa and R. F. Keep, “Photothrombotic infarction of caudate nucleus and parietal cortex,” Neuromethods 62, 183–191 (2011).
[Crossref]

A. M. I. Barth and I. Mody, “Changes in hippocampal neuronal activity during and after unilateral selective hippocampal ischemia in vivo,” J. Neurosci. 31(3), 851–860 (2011).
[Crossref] [PubMed]

2009 (1)

T. Kuroiwa, G. Xi, Y. Hua, T. N. Nagaraja, J. D. Fenstermacher, and R. F. Keep, “Development of a rat model of photothrombotic ischemia and infarction within the caudoputamen,” Stroke 40(1), 248–253 (2009).
[Crossref] [PubMed]

2007 (1)

J. D. Lozano, D. P. Abulafia, G. H. Danton, B. D. Watson, and W. D. Dietrich, “Characterization of a thromboembolic photochemical model of repeated stroke in mice,” J. Neurosci. Methods 162(1-2), 244–254 (2007).
[Crossref] [PubMed]

1999 (1)

U. Dirnagl, C. Iadecola, and M. A. Moskowitz, “Pathobiology of ischaemic stroke: an integrated view,” Trends Neurosci. 22(9), 391–397 (1999).
[Crossref] [PubMed]

1998 (1)

H. Nakase, K. Nagata, H. Otsuka, T. Sakaki, and O. Kempski, “Local cerebral blood flow autoregulation following “asymptomatic” cerebral venous occlusion in the rat,” J. Neurosurg. 89(1), 118–124 (1998).
[Crossref] [PubMed]

1996 (1)

H. Nakase, A. Heimann, and O. Kempski, “Local cerebral blood flow in a rat cortical vein occlusion model,” J. Cereb. Blood Flow Metab. 16(4), 720–728 (1996).
[Crossref] [PubMed]

1985 (1)

B. D. Watson, W. D. Dietrich, R. Busto, M. S. Wachtel, and M. D. Ginsberg, “Induction of reproducible brain infarction by photochemically initiated thrombosis,” Ann. Neurol. 17(5), 497–504 (1985).
[Crossref] [PubMed]

Abulafia, D. P.

J. D. Lozano, D. P. Abulafia, G. H. Danton, B. D. Watson, and W. D. Dietrich, “Characterization of a thromboembolic photochemical model of repeated stroke in mice,” J. Neurosci. Methods 162(1-2), 244–254 (2007).
[Crossref] [PubMed]

Barth, A. M. I.

A. M. I. Barth and I. Mody, “Changes in hippocampal neuronal activity during and after unilateral selective hippocampal ischemia in vivo,” J. Neurosci. 31(3), 851–860 (2011).
[Crossref] [PubMed]

Busto, R.

B. D. Watson, W. D. Dietrich, R. Busto, M. S. Wachtel, and M. D. Ginsberg, “Induction of reproducible brain infarction by photochemically initiated thrombosis,” Ann. Neurol. 17(5), 497–504 (1985).
[Crossref] [PubMed]

Danton, G. H.

J. D. Lozano, D. P. Abulafia, G. H. Danton, B. D. Watson, and W. D. Dietrich, “Characterization of a thromboembolic photochemical model of repeated stroke in mice,” J. Neurosci. Methods 162(1-2), 244–254 (2007).
[Crossref] [PubMed]

Dietrich, W. D.

J. D. Lozano, D. P. Abulafia, G. H. Danton, B. D. Watson, and W. D. Dietrich, “Characterization of a thromboembolic photochemical model of repeated stroke in mice,” J. Neurosci. Methods 162(1-2), 244–254 (2007).
[Crossref] [PubMed]

B. D. Watson, W. D. Dietrich, R. Busto, M. S. Wachtel, and M. D. Ginsberg, “Induction of reproducible brain infarction by photochemically initiated thrombosis,” Ann. Neurol. 17(5), 497–504 (1985).
[Crossref] [PubMed]

Dirnagl, U.

U. Dirnagl, C. Iadecola, and M. A. Moskowitz, “Pathobiology of ischaemic stroke: an integrated view,” Trends Neurosci. 22(9), 391–397 (1999).
[Crossref] [PubMed]

Fenstermacher, J. D.

T. Kuroiwa, G. Xi, Y. Hua, T. N. Nagaraja, J. D. Fenstermacher, and R. F. Keep, “Development of a rat model of photothrombotic ischemia and infarction within the caudoputamen,” Stroke 40(1), 248–253 (2009).
[Crossref] [PubMed]

Ginsberg, M. D.

B. D. Watson, W. D. Dietrich, R. Busto, M. S. Wachtel, and M. D. Ginsberg, “Induction of reproducible brain infarction by photochemically initiated thrombosis,” Ann. Neurol. 17(5), 497–504 (1985).
[Crossref] [PubMed]

Heimann, A.

H. Nakase, A. Heimann, and O. Kempski, “Local cerebral blood flow in a rat cortical vein occlusion model,” J. Cereb. Blood Flow Metab. 16(4), 720–728 (1996).
[Crossref] [PubMed]

Hua, Y.

T. Kuroiwa, G. Xi, Y. Hua, T. N. Nagaraja, J. D. Fenstermacher, and R. F. Keep, “Development of a rat model of photothrombotic ischemia and infarction within the caudoputamen,” Stroke 40(1), 248–253 (2009).
[Crossref] [PubMed]

Iadecola, C.

U. Dirnagl, C. Iadecola, and M. A. Moskowitz, “Pathobiology of ischaemic stroke: an integrated view,” Trends Neurosci. 22(9), 391–397 (1999).
[Crossref] [PubMed]

Keep, R. F.

T. Kuroiwa and R. F. Keep, “Photothrombotic infarction of caudate nucleus and parietal cortex,” Neuromethods 62, 183–191 (2011).
[Crossref]

T. Kuroiwa, G. Xi, Y. Hua, T. N. Nagaraja, J. D. Fenstermacher, and R. F. Keep, “Development of a rat model of photothrombotic ischemia and infarction within the caudoputamen,” Stroke 40(1), 248–253 (2009).
[Crossref] [PubMed]

Kempski, O.

H. Nakase, K. Nagata, H. Otsuka, T. Sakaki, and O. Kempski, “Local cerebral blood flow autoregulation following “asymptomatic” cerebral venous occlusion in the rat,” J. Neurosurg. 89(1), 118–124 (1998).
[Crossref] [PubMed]

H. Nakase, A. Heimann, and O. Kempski, “Local cerebral blood flow in a rat cortical vein occlusion model,” J. Cereb. Blood Flow Metab. 16(4), 720–728 (1996).
[Crossref] [PubMed]

Kuroiwa, T.

T. Kuroiwa and R. F. Keep, “Photothrombotic infarction of caudate nucleus and parietal cortex,” Neuromethods 62, 183–191 (2011).
[Crossref]

T. Kuroiwa, G. Xi, Y. Hua, T. N. Nagaraja, J. D. Fenstermacher, and R. F. Keep, “Development of a rat model of photothrombotic ischemia and infarction within the caudoputamen,” Stroke 40(1), 248–253 (2009).
[Crossref] [PubMed]

Lozano, J. D.

J. D. Lozano, D. P. Abulafia, G. H. Danton, B. D. Watson, and W. D. Dietrich, “Characterization of a thromboembolic photochemical model of repeated stroke in mice,” J. Neurosci. Methods 162(1-2), 244–254 (2007).
[Crossref] [PubMed]

Meier, R. J.

X.-D. Wang, O. S. Wolfbeis, and R. J. Meier, “Luminescent probes and sensors for temperature,” Chem. Soc. Rev. 42(19), 7834–7869 (2013).
[Crossref] [PubMed]

Mody, I.

A. M. I. Barth and I. Mody, “Changes in hippocampal neuronal activity during and after unilateral selective hippocampal ischemia in vivo,” J. Neurosci. 31(3), 851–860 (2011).
[Crossref] [PubMed]

Moskowitz, M. A.

U. Dirnagl, C. Iadecola, and M. A. Moskowitz, “Pathobiology of ischaemic stroke: an integrated view,” Trends Neurosci. 22(9), 391–397 (1999).
[Crossref] [PubMed]

Nagaraja, T. N.

T. Kuroiwa, G. Xi, Y. Hua, T. N. Nagaraja, J. D. Fenstermacher, and R. F. Keep, “Development of a rat model of photothrombotic ischemia and infarction within the caudoputamen,” Stroke 40(1), 248–253 (2009).
[Crossref] [PubMed]

Nagata, K.

H. Nakase, K. Nagata, H. Otsuka, T. Sakaki, and O. Kempski, “Local cerebral blood flow autoregulation following “asymptomatic” cerebral venous occlusion in the rat,” J. Neurosurg. 89(1), 118–124 (1998).
[Crossref] [PubMed]

Nakase, H.

H. Nakase, K. Nagata, H. Otsuka, T. Sakaki, and O. Kempski, “Local cerebral blood flow autoregulation following “asymptomatic” cerebral venous occlusion in the rat,” J. Neurosurg. 89(1), 118–124 (1998).
[Crossref] [PubMed]

H. Nakase, A. Heimann, and O. Kempski, “Local cerebral blood flow in a rat cortical vein occlusion model,” J. Cereb. Blood Flow Metab. 16(4), 720–728 (1996).
[Crossref] [PubMed]

Otsuka, H.

H. Nakase, K. Nagata, H. Otsuka, T. Sakaki, and O. Kempski, “Local cerebral blood flow autoregulation following “asymptomatic” cerebral venous occlusion in the rat,” J. Neurosurg. 89(1), 118–124 (1998).
[Crossref] [PubMed]

Sakaki, T.

H. Nakase, K. Nagata, H. Otsuka, T. Sakaki, and O. Kempski, “Local cerebral blood flow autoregulation following “asymptomatic” cerebral venous occlusion in the rat,” J. Neurosurg. 89(1), 118–124 (1998).
[Crossref] [PubMed]

Wachtel, M. S.

B. D. Watson, W. D. Dietrich, R. Busto, M. S. Wachtel, and M. D. Ginsberg, “Induction of reproducible brain infarction by photochemically initiated thrombosis,” Ann. Neurol. 17(5), 497–504 (1985).
[Crossref] [PubMed]

Wang, X.-D.

X.-D. Wang and O. S. Wolfbeis, “Fiber-optic chemical sensors and biosensors (2008-2012),” Anal. Chem. 85(2), 487–508 (2013).
[Crossref] [PubMed]

X.-D. Wang, O. S. Wolfbeis, and R. J. Meier, “Luminescent probes and sensors for temperature,” Chem. Soc. Rev. 42(19), 7834–7869 (2013).
[Crossref] [PubMed]

Watson, B. D.

J. D. Lozano, D. P. Abulafia, G. H. Danton, B. D. Watson, and W. D. Dietrich, “Characterization of a thromboembolic photochemical model of repeated stroke in mice,” J. Neurosci. Methods 162(1-2), 244–254 (2007).
[Crossref] [PubMed]

B. D. Watson, W. D. Dietrich, R. Busto, M. S. Wachtel, and M. D. Ginsberg, “Induction of reproducible brain infarction by photochemically initiated thrombosis,” Ann. Neurol. 17(5), 497–504 (1985).
[Crossref] [PubMed]

Wolfbeis, O. S.

X.-D. Wang, O. S. Wolfbeis, and R. J. Meier, “Luminescent probes and sensors for temperature,” Chem. Soc. Rev. 42(19), 7834–7869 (2013).
[Crossref] [PubMed]

X.-D. Wang and O. S. Wolfbeis, “Fiber-optic chemical sensors and biosensors (2008-2012),” Anal. Chem. 85(2), 487–508 (2013).
[Crossref] [PubMed]

Xi, G.

T. Kuroiwa, G. Xi, Y. Hua, T. N. Nagaraja, J. D. Fenstermacher, and R. F. Keep, “Development of a rat model of photothrombotic ischemia and infarction within the caudoputamen,” Stroke 40(1), 248–253 (2009).
[Crossref] [PubMed]

Anal. Chem. (1)

X.-D. Wang and O. S. Wolfbeis, “Fiber-optic chemical sensors and biosensors (2008-2012),” Anal. Chem. 85(2), 487–508 (2013).
[Crossref] [PubMed]

Ann. Neurol. (1)

B. D. Watson, W. D. Dietrich, R. Busto, M. S. Wachtel, and M. D. Ginsberg, “Induction of reproducible brain infarction by photochemically initiated thrombosis,” Ann. Neurol. 17(5), 497–504 (1985).
[Crossref] [PubMed]

Chem. Soc. Rev. (1)

X.-D. Wang, O. S. Wolfbeis, and R. J. Meier, “Luminescent probes and sensors for temperature,” Chem. Soc. Rev. 42(19), 7834–7869 (2013).
[Crossref] [PubMed]

J. Cereb. Blood Flow Metab. (1)

H. Nakase, A. Heimann, and O. Kempski, “Local cerebral blood flow in a rat cortical vein occlusion model,” J. Cereb. Blood Flow Metab. 16(4), 720–728 (1996).
[Crossref] [PubMed]

J. Neurosci. (1)

A. M. I. Barth and I. Mody, “Changes in hippocampal neuronal activity during and after unilateral selective hippocampal ischemia in vivo,” J. Neurosci. 31(3), 851–860 (2011).
[Crossref] [PubMed]

J. Neurosci. Methods (1)

J. D. Lozano, D. P. Abulafia, G. H. Danton, B. D. Watson, and W. D. Dietrich, “Characterization of a thromboembolic photochemical model of repeated stroke in mice,” J. Neurosci. Methods 162(1-2), 244–254 (2007).
[Crossref] [PubMed]

J. Neurosurg. (1)

H. Nakase, K. Nagata, H. Otsuka, T. Sakaki, and O. Kempski, “Local cerebral blood flow autoregulation following “asymptomatic” cerebral venous occlusion in the rat,” J. Neurosurg. 89(1), 118–124 (1998).
[Crossref] [PubMed]

Neuromethods (1)

T. Kuroiwa and R. F. Keep, “Photothrombotic infarction of caudate nucleus and parietal cortex,” Neuromethods 62, 183–191 (2011).
[Crossref]

Stroke (1)

T. Kuroiwa, G. Xi, Y. Hua, T. N. Nagaraja, J. D. Fenstermacher, and R. F. Keep, “Development of a rat model of photothrombotic ischemia and infarction within the caudoputamen,” Stroke 40(1), 248–253 (2009).
[Crossref] [PubMed]

Trends Neurosci. (1)

U. Dirnagl, C. Iadecola, and M. A. Moskowitz, “Pathobiology of ischaemic stroke: an integrated view,” Trends Neurosci. 22(9), 391–397 (1999).
[Crossref] [PubMed]

Other (5)

U. Dirnagl, “Rodent models of stroke,”, 7, (Springer, New York, 2010).

S. Senes, How We Manage Stroke in Australia (Australian Institute of Health and Welfare, 2006).

C. Mathers, D. M. Fat, and J. Boerma, The Global Burden of Disease: 2004 update (World Health Organization, 2008).

P. R. Hof, W. G. Young, F. E. Bloom, P. V. Belichenko, and M. R. Celio, Comparative Cytoarchitectonic Atlas of the C57BL/6 and 129/Sv Mouse Brains (Elsevier, Amsterdam, 2000).

C. A. Paul, B. Beltz and J. Berger-Sweeney, “The nissl stain: a stain for cell bodies in brain sections,” CSH protocols 2008, pdb. prot4805-pdb. prot4805 (2007).

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Figures (5)

Fig. 1
Fig. 1 - Experimental setup used for the FOPS experiments. Signal collected by the delivery fiber is analyzed by the CCD spectrometer in a backscattering geometry.
Fig. 2
Fig. 2 - (a) Normalized spectra collected in vitro in brain solutions for varied Rose Bengal concentrations (b) Expected wavelength values calculated for the data shown in Fig. 2(a) at different dye concentrations.
Fig. 3
Fig. 3 - Subcortical FOPS-induced lesions in the mouse brain (a) No infarction was observed in control mice injected with saline. Note the needle tract injury in the dorsal cortex caused by implantation of the fiber (arrowhead). (b) Injection of Rose Bengal coupled with low power illumination (12mW) resulted in a small lesion in the CA1 region of the hippocampus. (c) Injection of Rose Bengal coupled with high power illumination (43mW) resulted in extensive damage to the entire left striatum. Infarct locations are indicated by the dotted boundary. Scale bars = 1mm.
Fig. 4
Fig. 4 - (a) Spectra collected for different in vivo trials in the case of pre-bleaching, showing brain tissue autofluorescence (dashed lines), and after dye injection (solid lines). (b) Expected values for the spectra recorded from the pre-bleaching (circles) and post-dye injection (diamonds) trials. Right axis: estimated dye concentration determined by in vitro experiments. Dashed horizontal lines represent the mean value across each group.
Fig. 5
Fig. 5 - Kinetics of the total fluorescence intensity in the case of pre-bleaching, corresponding to brain tissue autofluorescence (dashed lines), and after dye injection, (solid lines) over the time of in-vivo trials.

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