Selective occlusion of the middle cerebral artery in mice by an intraluminal approach

Jianya Ma, Thaddeus Nowak

Research output: Contribution to journalArticle

Abstract

Background and Aims: A significant limitation in experimental stroke research is the heterogeneity of models employed, which complicates comparison of results among laboratories. This is a particular concern with intraluminal filament methods, both because filament design and fabrication vary and because the internal carotid artery (ICA) obstruction and diffuse ischemia they produce limit their application to short occlusion intervals, often in strains with appreciable collateral perfusion. Technical issues and strain variation concerns are amplified in mice. This report describes implementation of an occluding device for mice consisting of a silicone cylinder molded onto nylon filament that can traverse the ICA and enter the middle cerebral artery (MCA) to produce selective, reversible occlusion, extending recently published methodology for rats (1). Methods: Silicone cylinders of either 150 or 200 micron diameter and averaging 500 microns in length were molded onto 8-0 nylon filaments 10 mm in length. These were introduced into the cranial circulations of halothane-anesthetized adult (22-25 g) male mice of BALB/c, C57BL/6 and DBA/2J strains via the left external carotid artery as routinely described for intraluminal occlusions. Filaments were heparinized and mice received 100 units/kg subcutaneous heparin to reduce risk of secondary occlusion due to clot formation along the filament. After 24 hours brains were removed to assess filament position and circle of Willis anatomy, and to measure infarct volumes after triphenyltetrazolium staining. Results: Successful MCA entry was achieved in 70% (7/10) of BALB/c and 81% (47/58) of C57BL/6 using 200 micron devices, and 88% (7/8) of DBA/2J after diameter reduction to 150 microns. Failures resulted from acute branch angles at the origin of the MCA. Cortical infarct volumes were 86 +/- 14 and 39 +/- 4 cubic mm (mean +/- SD) in BALB/c and C57BL/6 mice, respectively, with no infarcts seen in DBA/2J mice, in agreement with previous data on relative vulnerability to focal ischemia in these strains (2,3). No mortality was observed. Conclusions: These results demonstrate the application of a refined intraluminal occlusion method in mice, using filaments manufactured to close tolerances. Dimensions can be modified to accommodate variations in vascular caliber among strains. Selective occlusion of the MCA permits the study of long durations of focal ischemia while maintaining the advantages of the widely used intraluminal approach.

Original languageEnglish (US)
JournalJournal of Cerebral Blood Flow and Metabolism
Volume27
Issue numberSUPPL. 1
StatePublished - Nov 13 2007

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Middle Cerebral Artery Infarction
Middle Cerebral Artery
Ischemia
Nylons
Internal Carotid Artery
Silicones
Circle of Willis
External Carotid Artery
Equipment and Supplies
Inbred DBA Mouse
Halothane
Inbred C57BL Mouse
Blood Vessels
Heparin
Anatomy
Perfusion
Stroke
Staining and Labeling
Mortality
Brain

All Science Journal Classification (ASJC) codes

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism

Cite this

Selective occlusion of the middle cerebral artery in mice by an intraluminal approach. / Ma, Jianya; Nowak, Thaddeus.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 27, No. SUPPL. 1, 13.11.2007.

Research output: Contribution to journalArticle

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abstract = "Background and Aims: A significant limitation in experimental stroke research is the heterogeneity of models employed, which complicates comparison of results among laboratories. This is a particular concern with intraluminal filament methods, both because filament design and fabrication vary and because the internal carotid artery (ICA) obstruction and diffuse ischemia they produce limit their application to short occlusion intervals, often in strains with appreciable collateral perfusion. Technical issues and strain variation concerns are amplified in mice. This report describes implementation of an occluding device for mice consisting of a silicone cylinder molded onto nylon filament that can traverse the ICA and enter the middle cerebral artery (MCA) to produce selective, reversible occlusion, extending recently published methodology for rats (1). Methods: Silicone cylinders of either 150 or 200 micron diameter and averaging 500 microns in length were molded onto 8-0 nylon filaments 10 mm in length. These were introduced into the cranial circulations of halothane-anesthetized adult (22-25 g) male mice of BALB/c, C57BL/6 and DBA/2J strains via the left external carotid artery as routinely described for intraluminal occlusions. Filaments were heparinized and mice received 100 units/kg subcutaneous heparin to reduce risk of secondary occlusion due to clot formation along the filament. After 24 hours brains were removed to assess filament position and circle of Willis anatomy, and to measure infarct volumes after triphenyltetrazolium staining. Results: Successful MCA entry was achieved in 70{\%} (7/10) of BALB/c and 81{\%} (47/58) of C57BL/6 using 200 micron devices, and 88{\%} (7/8) of DBA/2J after diameter reduction to 150 microns. Failures resulted from acute branch angles at the origin of the MCA. Cortical infarct volumes were 86 +/- 14 and 39 +/- 4 cubic mm (mean +/- SD) in BALB/c and C57BL/6 mice, respectively, with no infarcts seen in DBA/2J mice, in agreement with previous data on relative vulnerability to focal ischemia in these strains (2,3). No mortality was observed. Conclusions: These results demonstrate the application of a refined intraluminal occlusion method in mice, using filaments manufactured to close tolerances. Dimensions can be modified to accommodate variations in vascular caliber among strains. Selective occlusion of the MCA permits the study of long durations of focal ischemia while maintaining the advantages of the widely used intraluminal approach.",
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AU - Ma, Jianya

AU - Nowak, Thaddeus

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N2 - Background and Aims: A significant limitation in experimental stroke research is the heterogeneity of models employed, which complicates comparison of results among laboratories. This is a particular concern with intraluminal filament methods, both because filament design and fabrication vary and because the internal carotid artery (ICA) obstruction and diffuse ischemia they produce limit their application to short occlusion intervals, often in strains with appreciable collateral perfusion. Technical issues and strain variation concerns are amplified in mice. This report describes implementation of an occluding device for mice consisting of a silicone cylinder molded onto nylon filament that can traverse the ICA and enter the middle cerebral artery (MCA) to produce selective, reversible occlusion, extending recently published methodology for rats (1). Methods: Silicone cylinders of either 150 or 200 micron diameter and averaging 500 microns in length were molded onto 8-0 nylon filaments 10 mm in length. These were introduced into the cranial circulations of halothane-anesthetized adult (22-25 g) male mice of BALB/c, C57BL/6 and DBA/2J strains via the left external carotid artery as routinely described for intraluminal occlusions. Filaments were heparinized and mice received 100 units/kg subcutaneous heparin to reduce risk of secondary occlusion due to clot formation along the filament. After 24 hours brains were removed to assess filament position and circle of Willis anatomy, and to measure infarct volumes after triphenyltetrazolium staining. Results: Successful MCA entry was achieved in 70% (7/10) of BALB/c and 81% (47/58) of C57BL/6 using 200 micron devices, and 88% (7/8) of DBA/2J after diameter reduction to 150 microns. Failures resulted from acute branch angles at the origin of the MCA. Cortical infarct volumes were 86 +/- 14 and 39 +/- 4 cubic mm (mean +/- SD) in BALB/c and C57BL/6 mice, respectively, with no infarcts seen in DBA/2J mice, in agreement with previous data on relative vulnerability to focal ischemia in these strains (2,3). No mortality was observed. Conclusions: These results demonstrate the application of a refined intraluminal occlusion method in mice, using filaments manufactured to close tolerances. Dimensions can be modified to accommodate variations in vascular caliber among strains. Selective occlusion of the MCA permits the study of long durations of focal ischemia while maintaining the advantages of the widely used intraluminal approach.

AB - Background and Aims: A significant limitation in experimental stroke research is the heterogeneity of models employed, which complicates comparison of results among laboratories. This is a particular concern with intraluminal filament methods, both because filament design and fabrication vary and because the internal carotid artery (ICA) obstruction and diffuse ischemia they produce limit their application to short occlusion intervals, often in strains with appreciable collateral perfusion. Technical issues and strain variation concerns are amplified in mice. This report describes implementation of an occluding device for mice consisting of a silicone cylinder molded onto nylon filament that can traverse the ICA and enter the middle cerebral artery (MCA) to produce selective, reversible occlusion, extending recently published methodology for rats (1). Methods: Silicone cylinders of either 150 or 200 micron diameter and averaging 500 microns in length were molded onto 8-0 nylon filaments 10 mm in length. These were introduced into the cranial circulations of halothane-anesthetized adult (22-25 g) male mice of BALB/c, C57BL/6 and DBA/2J strains via the left external carotid artery as routinely described for intraluminal occlusions. Filaments were heparinized and mice received 100 units/kg subcutaneous heparin to reduce risk of secondary occlusion due to clot formation along the filament. After 24 hours brains were removed to assess filament position and circle of Willis anatomy, and to measure infarct volumes after triphenyltetrazolium staining. Results: Successful MCA entry was achieved in 70% (7/10) of BALB/c and 81% (47/58) of C57BL/6 using 200 micron devices, and 88% (7/8) of DBA/2J after diameter reduction to 150 microns. Failures resulted from acute branch angles at the origin of the MCA. Cortical infarct volumes were 86 +/- 14 and 39 +/- 4 cubic mm (mean +/- SD) in BALB/c and C57BL/6 mice, respectively, with no infarcts seen in DBA/2J mice, in agreement with previous data on relative vulnerability to focal ischemia in these strains (2,3). No mortality was observed. Conclusions: These results demonstrate the application of a refined intraluminal occlusion method in mice, using filaments manufactured to close tolerances. Dimensions can be modified to accommodate variations in vascular caliber among strains. Selective occlusion of the MCA permits the study of long durations of focal ischemia while maintaining the advantages of the widely used intraluminal approach.

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