Proximal occlusion of the middle cerebral artery in C57Black6 mice: relationship of patency of the posterior communicating artery, infarct evolution, and animal survival

Restricted access

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00

Object. The intraluminal suture model for focal cerebral ischemia is increasingly used, but not without problems. It causes hypothalamic injury, subarachnoid hemorrhage, and inadvertent premature reperfusion. The patency of the posterior communicating artery (PCoA) potentially affects the size of the infarct. In addition, survival at 1 week is unstable. The authors operated on C57Black6 mice to produce proximal middle cerebral artery occlusion (MCAO) so that drawbacks with the suture model could be circumvented.

Methods. The MCA segment just proximal to the olfactory branch was occluded either permanently or temporarily. After 1 hour of MCAO the infarct volume was significantly smaller than that found after 2 hours or in instances of permanent MCAO. The differences were assessed at 24 hours and 7 days after surgery (p < 0.05 and p < 0.001, respectively). The patency of the PCoA, as visualized using carbon black solution, did not correlate with the infarct size. Neurologically, the 1- and 2-hour MCAO groups displayed significantly less severe deficits than the permanent MCAO group on Days 1, 4, and 7 (p < 0.005 and p < 0.01, respectively). Although the infarct size, neurological deficits, and body weight loss were more severe in the permanent MCAO group, the survival rate at Day 7 was 80%.

Conclusions. This model provides not only a robust infarct size (which is not affected by the patency of the PCoA), but also a better survival rate.

Article Information

Contributor Notes

Address reprint requests to: Kazuhide Furuya, M.D., Department of Neurosurgery, University of Tokyo Hospital, 7–3–1 Hongo, Bunkyo-ku, Tokyo 113–8655, Japan. email: furuya-nsu@umin.ac.jp.
Headings
References
  • 1.

    Backhauss CKarkoutly CWelsch Met al: A mouse model of focal cerebral ischemia for screening neuroprotective drug effects. J Pharmacol Toxicol Methods 27:27321992Backhauss C Karkoutly C Welsch M et al: A mouse model of focal cerebral ischemia for screening neuroprotective drug effects. J Pharmacol Toxicol Methods 27:27–32 1992

    • Search Google Scholar
    • Export Citation
  • 2.

    Barone FCKnudsen DJNelson AHet al: Mouse strain differences in susceptibility to cerebral ischemia are related to cerebral vascular anatomy. J Cereb Blood Flow Metab 13:6836921993Barone FC Knudsen DJ Nelson AH et al: Mouse strain differences in susceptibility to cerebral ischemia are related to cerebral vascular anatomy. J Cereb Blood Flow Metab 13:683–692 1993

    • Search Google Scholar
    • Export Citation
  • 3.

    Butler H: The development of mammalian dural venous sinuses with especial reference to the post-glenoid vein. J Anat 102:33561967Butler H: The development of mammalian dural venous sinuses with especial reference to the post-glenoid vein. J Anat 102:33–56 1967

    • Search Google Scholar
    • Export Citation
  • 4.

    Chen HChopp MZhang ZGet al: The effect of hypothermia on transient middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab 12:6216281992Chen H Chopp M Zhang ZG et al: The effect of hypothermia on transient middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab 12:621–628 1992

    • Search Google Scholar
    • Export Citation
  • 5.

    Chiamulera CTerron AReggiani Aet al: Qualitative and quantitative analysis of the progressive cerebral damage after middle cerebral artery occlusion in mice. Brain Res 606:2512581993Chiamulera C Terron A Reggiani A et al: Qualitative and quantitative analysis of the progressive cerebral damage after middle cerebral artery occlusion in mice. Brain Res 606:251–258 1993

    • Search Google Scholar
    • Export Citation
  • 6.

    Coyle P: Middle cerebral artery occlusion in the young rat. Stroke 13:8558591982Coyle P: Middle cerebral artery occlusion in the young rat. Stroke 13:855–859 1982

    • Search Google Scholar
    • Export Citation
  • 7.

    Fujii MHara HMeng Wet al: Strain-related differences in susceptibility to transient forebrain ischemia in SV-129 and C57black/6 mice. Stroke 28:180518111997Fujii M Hara H Meng W et al: Strain-related differences in susceptibility to transient forebrain ischemia in SV-129 and C57black/6 mice. Stroke 28:1805–1811 1997

    • Search Google Scholar
    • Export Citation
  • 8.

    Garcia JHYoshida YChen Het al: Progression from ischemic injury to infarct following middle cerebral artery occlusion in the rat. Am J Pathol 142:6236351993Garcia JH Yoshida Y Chen H et al: Progression from ischemic injury to infarct following middle cerebral artery occlusion in the rat. Am J Pathol 142:623–635 1993

    • Search Google Scholar
    • Export Citation
  • 9.

    Gerlai R: Gene-targeting studies of mammalian behavior: is it the mutation or the background genotype? Trends Neurosci 19:1771811996Gerlai R: Gene-targeting studies of mammalian behavior: is it the mutation or the background genotype? Trends Neurosci 19:177–181 1996

    • Search Google Scholar
    • Export Citation
  • 10.

    Hara HHuang PLPanahian Net al: Reduced brain edema and infarction volume in mice lacking the neuronal isoform of nitric oxide synthase after transient MCA occlusion. J Cereb Blood Flow Metab 16:6056111996Hara H Huang PL Panahian N et al: Reduced brain edema and infarction volume in mice lacking the neuronal isoform of nitric oxide synthase after transient MCA occlusion. J Cereb Blood Flow Metab 16:605–611 1996

    • Search Google Scholar
    • Export Citation
  • 11.

    Hara TMies GHossmann KA: Effect of thrombolysis on the dynamics of infarct evolution after clot embolism of middle cerebral artery in mice. J Cereb Blood Flow Metab 20:148314912000Hara T Mies G Hossmann KA: Effect of thrombolysis on the dynamics of infarct evolution after clot embolism of middle cerebral artery in mice. J Cereb Blood Flow Metab 20:1483–1491 2000

    • Search Google Scholar
    • Export Citation
  • 12.

    He ZYamawaki TYang Set al: Experimental model of small deep infarcts involving the hypothalamus in rats: changes in body temperature and postural reflex. Stroke 30:274327511999He Z Yamawaki T Yang S et al: Experimental model of small deep infarcts involving the hypothalamus in rats: changes in body temperature and postural reflex. Stroke 30:2743–2751 1999

    • Search Google Scholar
    • Export Citation
  • 13.

    Huang JKim LJPoisik Aet al: Titration of postischemic cerebral hypoperfusion by variation of ischemic severity in a murine model of stroke. Neurosurgery 45:3283331999Huang J Kim LJ Poisik A et al: Titration of postischemic cerebral hypoperfusion by variation of ischemic severity in a murine model of stroke. Neurosurgery 45:328–333 1999

    • Search Google Scholar
    • Export Citation
  • 14.

    Huang ZHuang PLPanahian Net al: Effects of cerebral ischemia in mice deficient in neuronal nitric oxide synthase. Science 265:188318851994Huang Z Huang PL Panahian N et al: Effects of cerebral ischemia in mice deficient in neuronal nitric oxide synthase. Science 265:1883–1885 1994

    • Search Google Scholar
    • Export Citation
  • 15.

    Hudgins WRGarcia JH: Transorbital approach to the middle cerebral artery of the squirrel monkey: a technique for experimental cerebral infarction applicable to ultrastructural studies. Stroke 1:1071111970Hudgins WR Garcia JH: Transorbital approach to the middle cerebral artery of the squirrel monkey: a technique for experimental cerebral infarction applicable to ultrastructural studies. Stroke 1:107–111 1970

    • Search Google Scholar
    • Export Citation
  • 16.

    Kano MMoskowitz MAYokota M: Parasympathetic denervation of rat pial vessels significantly increases infarction volume following middle cerebral artery occlusion. J Cereb Blood Flow Metab 11:6286371991Kano M Moskowitz MA Yokota M: Parasympathetic denervation of rat pial vessels significantly increases infarction volume following middle cerebral artery occlusion. J Cereb Blood Flow Metab 11:628–637 1991

    • Search Google Scholar
    • Export Citation
  • 17.

    Kilic EHermann DMHossmann KA: A reproducible model of thromboembolic stroke in mice. Neuroreport 9:296729701998Kilic E Hermann DM Hossmann KA: A reproducible model of thromboembolic stroke in mice. Neuroreport 9:2967–2970 1998

    • Search Google Scholar
    • Export Citation
  • 18.

    Kitagawa KMatsumoto MKuwabara Ket al: Delayed, but marked, expression of apolipoprotein E is involved in tissue clearance after cerebral infarction. J Cereb Blood Flow Metab 21:119912072001Kitagawa K Matsumoto M Kuwabara K et al: Delayed but marked expression of apolipoprotein E is involved in tissue clearance after cerebral infarction. J Cereb Blood Flow Metab 21:1199–1207 2001

    • Search Google Scholar
    • Export Citation
  • 19.

    Kitagawa KMatsumoto MMabuchi Tet al: Deficiency of intercellular adhesion molecule 1 attenuates microcirculatory disturbance and infarction size in focal cerebral ischemia. J Cereb Blood Flow Metab 18:133613451998Kitagawa K Matsumoto M Mabuchi T et al: Deficiency of intercellular adhesion molecule 1 attenuates microcirculatory disturbance and infarction size in focal cerebral ischemia. J Cereb Blood Flow Metab 18:1336–1345 1998

    • Search Google Scholar
    • Export Citation
  • 20.

    Kitagawa KMatsumoto MYang Get al: Cerebral ischemia after bilateral carotid artery occlusion and intraluminal suture occlusion in mice: evaluation of the patency of the posterior communicating artery. J Cereb Blood Flow Metab 18:5705791998Kitagawa K Matsumoto M Yang G et al: Cerebral ischemia after bilateral carotid artery occlusion and intraluminal suture occlusion in mice: evaluation of the patency of the posterior communicating artery. J Cereb Blood Flow Metab 18:570–579 1998

    • Search Google Scholar
    • Export Citation
  • 21.

    Koizumi JYoshida YNakazawa Tet al: Experimental studies of ischemic brain edema, I: a new experimental model of cerebral embolism in rats in which recirculation can be introduced in the ischemic area. Jpn J Stroke 8:181986Koizumi J Yoshida Y Nakazawa T et al: Experimental studies of ischemic brain edema I: a new experimental model of cerebral embolism in rats in which recirculation can be introduced in the ischemic area. Jpn J Stroke 8:1–8 1986

    • Search Google Scholar
    • Export Citation
  • 22.

    Kuge YMinematsu KYamaguchi Tet al: Nylon monofilament for intraluminal middle cerebral artery occlusion in rats. Stroke 26:165516581995Kuge Y Minematsu K Yamaguchi T et al: Nylon monofilament for intraluminal middle cerebral artery occlusion in rats. Stroke 26:1655–1658 1995

    • Search Google Scholar
    • Export Citation
  • 23.

    Laing RJJakubowski JLaing RW: Middle cerebral artery occlusion without craniectomy in rats. Which method works best? Stroke 24:2942981993Laing RJ Jakubowski J Laing RW: Middle cerebral artery occlusion without craniectomy in rats. Which method works best? Stroke 24:294–298 1993

    • Search Google Scholar
    • Export Citation
  • 24.

    Leach MJSwan JHEisenthal Det al: BW619C89, a glutamate release inhibitor, protects against focal cerebral ischemic damage. Stroke 24:106310671993Leach MJ Swan JH Eisenthal D et al: BW619C89 a glutamate release inhibitor protects against focal cerebral ischemic damage. Stroke 24:1063–1067 1993

    • Search Google Scholar
    • Export Citation
  • 25.

    Longa EZWeinstein PRCarlson Set al: Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 20:84911989Longa EZ Weinstein PR Carlson S et al: Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 20:84–91 1989

    • Search Google Scholar
    • Export Citation
  • 26.

    MacKenzie ETScatton B: Cerebral circulatory and metabolic effects of perivascular neurotransmitters. CRC Crit Rev Clin Neurobiol 2:3574191987MacKenzie ET Scatton B: Cerebral circulatory and metabolic effects of perivascular neurotransmitters. CRC Crit Rev Clin Neurobiol 2:357–419 1987

    • Search Google Scholar
    • Export Citation
  • 27.

    Maeda KHata RHossmann KA: Differences in the cerebrovascular anatomy of C57black/6 and SV129 mice. Neuroreport 9:131713191998Maeda K Hata R Hossmann KA: Differences in the cerebrovascular anatomy of C57black/6 and SV129 mice. Neuroreport 9:1317–1319 1998

    • Search Google Scholar
    • Export Citation
  • 28.

    Murakami KKondo TKawase Met al: The development of a new mouse model of global ischemia: focus on the relationships between ischemia duration, anesthesia, cerebral vasculature, and neuronal injury following global ischemia in mice. Brain Res 780:3043101998Murakami K Kondo T Kawase M et al: The development of a new mouse model of global ischemia: focus on the relationships between ischemia duration anesthesia cerebral vasculature and neuronal injury following global ischemia in mice. Brain Res 780:304–310 1998

    • Search Google Scholar
    • Export Citation
  • 29.

    Nagasawa HKogure K: Correlation between cerebral blood flow and histologic changes in a new rat model of middle cerebral artery occlusion. Stroke 20:103710431989Nagasawa H Kogure K: Correlation between cerebral blood flow and histologic changes in a new rat model of middle cerebral artery occlusion. Stroke 20:1037–1043 1989

    • Search Google Scholar
    • Export Citation
  • 30.

    Paxinos GFranklin KBJ: The Mouse Brain in Stereotaxic Coordinatesed 2. San Diego: Academic Press2001Paxinos G Franklin KBJ: The Mouse Brain in Stereotaxic Coordinates ed 2. San Diego: Academic Press 2001

    • Search Google Scholar
    • Export Citation
  • 31.

    Roof RLSchielke GPRen Xet al: A comparison of long-term functional outcome after 2 middle cerebral artery occlusion models in rats. Stroke 32:264826572001Roof RL Schielke GP Ren X et al: A comparison of long-term functional outcome after 2 middle cerebral artery occlusion models in rats. Stroke 32:2648–2657 2001

    • Search Google Scholar
    • Export Citation
  • 32.

    Rubino GJYoung W: Ischemic cortical lesions after permanent occlusion of individual middle cerebral artery branches in rats. Stroke 19:8708771988Rubino GJ Young W: Ischemic cortical lesions after permanent occlusion of individual middle cerebral artery branches in rats. Stroke 19:870–877 1988

    • Search Google Scholar
    • Export Citation
  • 33.

    Schmid-Elsaesser RZausinger SHungerhuber Eet al: A critical reevaluation of the intraluminal thread model of focal cerebral ischemia: evidence of inadvertent premature reperfusion and subarachnoid hemorrhage in rats by laser-Doppler flowmetry. Stroke 29:216221701998Schmid-Elsaesser R Zausinger S Hungerhuber E et al: A critical reevaluation of the intraluminal thread model of focal cerebral ischemia: evidence of inadvertent premature reperfusion and subarachnoid hemorrhage in rats by laser-Doppler flowmetry. Stroke 29:2162–2170 1998

    • Search Google Scholar
    • Export Citation
  • 34.

    Scremin OU: The vascular anatomy of the rat's hypothalamus in stereotaxic coordinates. J Comp Neurol 139:31521970Scremin OU: The vascular anatomy of the rat's hypothalamus in stereotaxic coordinates. J Comp Neurol 139:31–52 1970

    • Search Google Scholar
    • Export Citation
  • 35.

    Silva AJSimpson EMTakahashi JSet al: Mutant mice and neuroscience: recommendations concerning genetic background. Banbury Conference on genetic background in mice. Neuron 19:7557591997Silva AJ Simpson EM Takahashi JS et al: Mutant mice and neuroscience: recommendations concerning genetic background. Banbury Conference on genetic background in mice. Neuron 19:755–759 1997

    • Search Google Scholar
    • Export Citation
  • 36.

    Swanson RAMorton MTTsao-Wu Get al: A semiautomated method for measuring brain infarct volume. J Cereb Blood Flow Metab 10:2902931990Swanson RA Morton MT Tsao-Wu G et al: A semiautomated method for measuring brain infarct volume. J Cereb Blood Flow Metab 10:290–293 1990

    • Search Google Scholar
    • Export Citation
  • 37.

    Tamura AKawai KTakagi K: Animal models used in cerebral ischemia and stroke research in Ter Horst GJKorf J (eds): Clinical Pharmacology of Cerebral Ischemia. Totowa NJ: Humana Press1997 pp 265294Tamura A Kawai K Takagi K: Animal models used in cerebral ischemia and stroke research in Ter Horst GJ Korf J (eds): Clinical Pharmacology of Cerebral Ischemia. Totowa NJ: Humana Press 1997 pp 265–294

    • Search Google Scholar
    • Export Citation
  • 38.

    Welsh FASakamoto TMcKee AEet al: Effect of lactacidosis on pyridine nucleotide stability during ischemia in mouse brain. J Neurochem 49:8468511987Welsh FA Sakamoto T McKee AE et al: Effect of lactacidosis on pyridine nucleotide stability during ischemia in mouse brain. J Neurochem 49:846–851 1987

    • Search Google Scholar
    • Export Citation
  • 39.

    Yang GKitagawa KMatsushita Ket al: C57BL/6 strain is most susceptible to cerebral ischemia following bilateral common carotid occlusion among seven mouse strains: selective neuronal death in the murine transient forebrain ischemia. Brain Res 752:2092181997Yang G Kitagawa K Matsushita K et al: C57BL/6 strain is most susceptible to cerebral ischemia following bilateral common carotid occlusion among seven mouse strains: selective neuronal death in the murine transient forebrain ischemia. Brain Res 752:209–218 1997

    • Search Google Scholar
    • Export Citation
  • 40.

    Zhao QMemezawa HSmith MLet al: Hyperthermia complicates middle cerebral artery occlusion induced by an intraluminal filament. Brain Res 649:2532591994Zhao Q Memezawa H Smith ML et al: Hyperthermia complicates middle cerebral artery occlusion induced by an intraluminal filament. Brain Res 649:253–259 1994

    • Search Google Scholar
    • Export Citation
Cited By
Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 394 272 30
Full Text Views 220 38 4
PDF Downloads 126 18 3
EPUB Downloads 0 0 0
PubMed
Google Scholar