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Optical imaging to map blood-brain barrier leakage.

Jaffer H, Adjei IM, Labhasetwar V - Sci Rep (2013)

Bottom Line: Vascular leakage in the brain is a major complication associated with brain injuries and certain pathological conditions due to disruption of the blood-brain barrier (BBB).The new method is quantitative, simple to use, requires no tissue processing, and can map the degree of vascular leakage in different brain locations.The high sensitivity of our method could potentially provide new opportunities to study BBB leakage in different pathological conditions and to test the efficacy of various therapeutic strategies to protect the BBB.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195.

ABSTRACT
Vascular leakage in the brain is a major complication associated with brain injuries and certain pathological conditions due to disruption of the blood-brain barrier (BBB). We have developed an optical imaging method, based on excitation and emission spectra of Evans Blue dye, that is >1000-fold more sensitive than conventional ultraviolet spectrophotometry. We used a rat thromboembolic stroke model to validate the usefulness of our method for vascular leakage. Optical imaging data show that vascular leakage varies in different areas of the post-stroke brain and that administering tissue plasminogen activator causes further leakage. The new method is quantitative, simple to use, requires no tissue processing, and can map the degree of vascular leakage in different brain locations. The high sensitivity of our method could potentially provide new opportunities to study BBB leakage in different pathological conditions and to test the efficacy of various therapeutic strategies to protect the BBB.

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Effect of t-PA on vascular leakage in animals with stroke.(a) Control animals without stroke but received EB. (b) Animals with stroke, imaged 5 hrs after induction of stroke and 2 hrs after EB injection. (c) Animals with stroke that received t-PA (2 mg/kg) administered via intracarotid injection. (d) Quantification of optical signal of all the brain slices from the above groups and normal animal (without stroke, data from Fig. 4d) which received the same dose of t-PA via carotid artery. Data shown are the cumulative signal from all the brain slices normalized to pixel area. A filter paper disc loaded with 20 ng EB dye as an internal standard. Data are shown as mean ± s.e.m., n = 3. *p = 0.036, control vs. stroke; **p = 0.001, control vs. stroke + t-PA (2 mg/kg) administered through intracarotid route; ***p = 0.018, stroke vs. stroke + t-PA (2 mg/kg) administered through intracarotid route; ****p = 0.04 control + t-PA vs. stroke + t-PA (2 mg/kg) administered through intracarotid route.
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f5: Effect of t-PA on vascular leakage in animals with stroke.(a) Control animals without stroke but received EB. (b) Animals with stroke, imaged 5 hrs after induction of stroke and 2 hrs after EB injection. (c) Animals with stroke that received t-PA (2 mg/kg) administered via intracarotid injection. (d) Quantification of optical signal of all the brain slices from the above groups and normal animal (without stroke, data from Fig. 4d) which received the same dose of t-PA via carotid artery. Data shown are the cumulative signal from all the brain slices normalized to pixel area. A filter paper disc loaded with 20 ng EB dye as an internal standard. Data are shown as mean ± s.e.m., n = 3. *p = 0.036, control vs. stroke; **p = 0.001, control vs. stroke + t-PA (2 mg/kg) administered through intracarotid route; ***p = 0.018, stroke vs. stroke + t-PA (2 mg/kg) administered through intracarotid route; ****p = 0.04 control + t-PA vs. stroke + t-PA (2 mg/kg) administered through intracarotid route.

Mentions: Animals with stroke demonstrated significantly greater vascular leakage than normal animals, with high intensity seen in the core of the infarcted area (Fig. 5a vs. 5b). Administration of t-PA (2 mg/kg via carotid artery) in stroke condition further increased vascular leakage, as evident from the intense dark red areas (Fig. 5b vs. 5c). Comparing signals from normal animals (without stroke induction) that had received the same dose of t-PA, it is clear that administration of t-PA under stroke conditions further aggravates vascular leakage (Fig. 4d vs. Fig. 5c). Quantitative analysis of signal intensities from all brain slices demonstrates a >2.5-fold increase in signal intensities in animals with stroke and a 4.5-fold increase in stroke animals that had also received t-PA vs. sham control animals. The data also show that vascular leakage in normal animals (without stroke) that received t-PA (2 mg/kg) via carotid artery was almost similar to that in animals with stroke (Fig. 5d).


Optical imaging to map blood-brain barrier leakage.

Jaffer H, Adjei IM, Labhasetwar V - Sci Rep (2013)

Effect of t-PA on vascular leakage in animals with stroke.(a) Control animals without stroke but received EB. (b) Animals with stroke, imaged 5 hrs after induction of stroke and 2 hrs after EB injection. (c) Animals with stroke that received t-PA (2 mg/kg) administered via intracarotid injection. (d) Quantification of optical signal of all the brain slices from the above groups and normal animal (without stroke, data from Fig. 4d) which received the same dose of t-PA via carotid artery. Data shown are the cumulative signal from all the brain slices normalized to pixel area. A filter paper disc loaded with 20 ng EB dye as an internal standard. Data are shown as mean ± s.e.m., n = 3. *p = 0.036, control vs. stroke; **p = 0.001, control vs. stroke + t-PA (2 mg/kg) administered through intracarotid route; ***p = 0.018, stroke vs. stroke + t-PA (2 mg/kg) administered through intracarotid route; ****p = 0.04 control + t-PA vs. stroke + t-PA (2 mg/kg) administered through intracarotid route.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814906&req=5

f5: Effect of t-PA on vascular leakage in animals with stroke.(a) Control animals without stroke but received EB. (b) Animals with stroke, imaged 5 hrs after induction of stroke and 2 hrs after EB injection. (c) Animals with stroke that received t-PA (2 mg/kg) administered via intracarotid injection. (d) Quantification of optical signal of all the brain slices from the above groups and normal animal (without stroke, data from Fig. 4d) which received the same dose of t-PA via carotid artery. Data shown are the cumulative signal from all the brain slices normalized to pixel area. A filter paper disc loaded with 20 ng EB dye as an internal standard. Data are shown as mean ± s.e.m., n = 3. *p = 0.036, control vs. stroke; **p = 0.001, control vs. stroke + t-PA (2 mg/kg) administered through intracarotid route; ***p = 0.018, stroke vs. stroke + t-PA (2 mg/kg) administered through intracarotid route; ****p = 0.04 control + t-PA vs. stroke + t-PA (2 mg/kg) administered through intracarotid route.
Mentions: Animals with stroke demonstrated significantly greater vascular leakage than normal animals, with high intensity seen in the core of the infarcted area (Fig. 5a vs. 5b). Administration of t-PA (2 mg/kg via carotid artery) in stroke condition further increased vascular leakage, as evident from the intense dark red areas (Fig. 5b vs. 5c). Comparing signals from normal animals (without stroke induction) that had received the same dose of t-PA, it is clear that administration of t-PA under stroke conditions further aggravates vascular leakage (Fig. 4d vs. Fig. 5c). Quantitative analysis of signal intensities from all brain slices demonstrates a >2.5-fold increase in signal intensities in animals with stroke and a 4.5-fold increase in stroke animals that had also received t-PA vs. sham control animals. The data also show that vascular leakage in normal animals (without stroke) that received t-PA (2 mg/kg) via carotid artery was almost similar to that in animals with stroke (Fig. 5d).

Bottom Line: Vascular leakage in the brain is a major complication associated with brain injuries and certain pathological conditions due to disruption of the blood-brain barrier (BBB).The new method is quantitative, simple to use, requires no tissue processing, and can map the degree of vascular leakage in different brain locations.The high sensitivity of our method could potentially provide new opportunities to study BBB leakage in different pathological conditions and to test the efficacy of various therapeutic strategies to protect the BBB.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195.

ABSTRACT
Vascular leakage in the brain is a major complication associated with brain injuries and certain pathological conditions due to disruption of the blood-brain barrier (BBB). We have developed an optical imaging method, based on excitation and emission spectra of Evans Blue dye, that is >1000-fold more sensitive than conventional ultraviolet spectrophotometry. We used a rat thromboembolic stroke model to validate the usefulness of our method for vascular leakage. Optical imaging data show that vascular leakage varies in different areas of the post-stroke brain and that administering tissue plasminogen activator causes further leakage. The new method is quantitative, simple to use, requires no tissue processing, and can map the degree of vascular leakage in different brain locations. The high sensitivity of our method could potentially provide new opportunities to study BBB leakage in different pathological conditions and to test the efficacy of various therapeutic strategies to protect the BBB.

Show MeSH
Related in: MedlinePlus