Animal models of ischemic stroke

Animal models of ischemic stroke

Animal models of ischemic stroke are procedures inducing cerebral ischemia. The aim is the study of basic processes or potential therapeutic interventions in this disease, and the extension of the pathophysiological knowledge on and/or the improvement of medical treatment of human ischemic stroke.Ischemic stroke has a complex pathophysiology involving the interplay of many different cells and tissues such as neurons, glia, endothelium, and the immune system. These events cannot be mimicked satisfactorily in vitro yet. Thus a large portion of stroke research is conducted on animals.

=Overview=Several models in different species are currently known to produce cerebral ischemiaref|graham2004. Global ischemia models, both complete and incomplete, tend to be easier to perform. However, they are less immediately relevant to human stroke than the focal stroke models, because global ischemia is not a common feature of human stroke. However, in various settings global ischemia is also relevant, e.g. in global anoxic brain damage due to cardiac arrest. Different species also vary in their susceptibility to the various types of ischemic insults. An example is gerbils. They do not have a Circle of Willis and stroke can be induced by common carotid artery occlusion alone.

Mechanisms of inducing ischemic stroke

Some of the mechanisms which have been used are:
*Complete global ischemia
**Decapitation
**Aorta/vena cava occlusion
**External neck torniquet or cuff
**Cardiac arrest
*Incomplete global ischemia
**Hemorrhage or hypotension
**Hypoxic ischemia
**Intracranial hypertension and common carotid artery occlusion
**Two-vessel occlusion and hypotension
**Four-vessel occlusion
**Unilateral common carotid artery occlusion (in some species only)
*Focal cerebral ischemia
**Middle cerebral artery occlusion
**Spontaneous brain infarction (in spontaneously hypertensive rats)
**Macrosphere embolization
*Multifocal cerebral ischemia
**Blood clot embolization
**Microsphere embolization
**Photothrombosis

Hypoxic Ischemia models

One of the most commonly used animal models of hypoxic ischemia was originally described by Levine in 1960 and later refined by Rice et al., in 1981. This approach is useful to study hypoxic ischemia in the developing brain, since newborn rat pups are utilized in this model. Briefly, 7 day old rat pups undergo a permanent unilateral carotid artery ligation with a subsequent 3 hour exposure to a hypoxic environment (8% oxygen). This model creates a unilateral infarct in the hemisphere ipsilateral to the ligation, since the hypoxia alone is subthreshold for injury at this age. The area of injury is typically concentrated in periventricular regions of the brain, especially cortical and hippocampal areas.

Focal ischemia models

They are divided into techniques including reperfusion of the ischemic tissue (transient focal cerebral ischemia) and those without reperfusion (permanent focal cerebral ischemia). The following models are established ref|carmichael2005:
*Middle cerebral artery occlusion (MCAO)
**MCAO avoiding craniotomy
***Embolic middle cerebral artery occlusion
***Endovascular filament middle cerebral artery occlusion (transient or permanent)
**MCAO involving craniotomy
***Permanent transcranial middle cerebral artery occlusion
***Transient transcranial middle cerebral artery occlusion
*Direct tissue damage
**Cerebrocortical photothrombosis

Embolic middle cerebral artery occlusion

Middle cerebral artery (MCA) occlusion is achieved in this model by injecting particles like blood clots (thrombembolic MCAO) or artificial spheres into the carotid artery of animals as an animal model of ischemic stroke. Thromembolic MCAO is achieved either by injecting clots that were formed in vitro ref|beech2001or by endovascular instillation of thrombin for in situ clotting ref|zhang1997. The thrombembolic model is closest to the pathophysiology of human cardioembolic stroke. When injecting spheres into the cerebral circulation, their size determines the pattern of brain infarction: Macrospheres (300 – 400 µm) induce infarcts similar to those achieved by occlusion of the proximal MCA ref|gerriets2003, whereas microsphere (~ 50 µm) injection results in distal, diffuse embolism ref|mayzeloreg2004. However, the quality of MCAO – and thus the volume of brain infarcts – is very variable, a fact which is further aggravated by a certain rate of spontaneous lysis of injected blood clots.

Endovascular filament middle cerebral artery occlusion

The technique of endovascular filament (intraluminal suture) MCAO as an animal model of ischemic stroke was described first by Koizumi ref|koizumi1986. It is applied to rats and mice. A piece of surgical filament is introduced into the internal carotid artery and forwarded until the tip occludes the origin of the middle cerebral artery, resulting in a cessation of blood flow and subsequent brain infarction in its area of supply. If the suture is removed after a certain interval, reperfusion is achieved (transient MCAO); if the filament is left in place the procedure is suitable as model of permanent MCAO, too. The most common modification is based on Longa (1989) ref|longa1989 who described filament introduction via the external carotid artery, allowing closure of the access point with preserved blood supply via the common and internal carotid artery to the brain after the removal of the filament. Known pitfalls of this method are insufficient occlusion, subarachnoid hemorrhage ref|schmidelsaesser1998, hyperthermia ref|gerriets2004, and necrosis of the ipsilateral extracranial tissue ref|dittmar2003. Filament MCAO is not applicable to all rat strains ref|dittmar2006.

Permanent transcranial middle cerebral artery occlusion

In this animal model of ischemic stroke the middle cerebral artery (MCA) is surgically dissected and subsequently permanently occluded, e.g. by electrocautery or ligation. Occlusion can be performed on the proximal ref|tamura1981 or distal ref|chen1986 part of the MCA. In the latter, ischemic damage is restricted to the cerebral cortex. MCAO can be combined with temporal or permanent common carotid artery occlusion. These models require a small craniotomy.

Transient transcranial middle cerebral artery occlusion

The technique of modeling ischemic stroke by transient transcranial MCAO is similar to that of permanent transcranial MCAO, with the MCA being reperfused after a defined period of focal cerebral ischemia ref|buchan1992. Like permanent MCAO, craniotomy is required and common carotid artery (CCA) occlusion can be combined. Occluding one MCA and both CCAs is referred to as the three vessel occlusion model of focal cerebral ischemia.

Cerebrocortical photothrombosis

Photothrombotic models of ischemic stroke use local intravascular photocoagulation of circumscribed cortical areas. After intravenous injection of photosensitive dyes like rose-bengal, the brain is irradiated with through the intact skull, leading to photochemical occlusion of the irradiated vessels with secondary tissue ischemia ref|watson1985.

ee also

*animal models of stroke

References

*cite journal
author = Beech, J. S., S. C. Williams, C. A. Campbell, P. M. Bath, A. A. Parsons, A. J. Hunter, D. K. Menon
year = 2001
month =
title = Further characterisation of a thromboembolic model of stroke in the rat.
journal = Brain Res
volume = 895
issue =
pages = 18–24
id =
url = http://linkinghub.elsevier.com/retrieve/pii/S0006-8993(00)03331-X
doi = 10.1016/S0006-8993(00)03331-X

*cite journal
author = Buchan, A. M., D. Xue, A. Slivka
year = 1992
month =
title = A new model of temporary focal neocortical ischemia in the rat
journal = Stroke
volume = 23
issue =
pages = 273–9
id =
url = http://stroke.ahajournals.org/cgi/content/abstract/23/2/273
pmid = 1561658

*cite journal
author = Carmichael, S. T.
year = 2005
month =
title = Rodent models of focal stroke: size, mechanism, and purpose
journal = NeuroRx
volume = 2
issue =
pages = 396–409
id =
url = http://www.neurorx.org/cgi/reprint/2/3/396
doi = 10.1602/neurorx.2.3.396

*cite journal
author = Chen, S. T., C. Y. Hsu, E. L. Hogan, H. Maricq, J. D. Balentine
year = 1986
month =
title = A model of focal ischemic stroke in the rat: reproducible extensive cortical infarction
journal = Stroke
volume = 17
issue =
pages = 738–43
id =
url = http://stroke.ahajournals.org/cgi/content/abstract/17/4/738
pmid = 2943059

*cite journal
author = Dittmar, M., T. Spruss, G. Schuierer, M. Horn
year =
month =
title = External carotid artery territory ischemia impairs outcome in the endovascular filament model of middle cerebral artery occlusion in rats
journal = Stroke
volume = 34
issue =
pages = 2252–7
id =
url = http://stroke.ahajournals.org/cgi/content/abstract/34/9/2252
doi = 10.1161/01.STR.0000083625.54851.9A

*cite journal
author = Dittmar, M. S., B. Vatankhah, N. P. Fehm, G. Schuierer, U. Bogdahn, M. Horn, F. Schlachetzki
year = 2006
month =
title = Fischer-344 rats are unsuitable for the MCAO filament model due to their cerebrovascular anatomy
journal = J Neurosci Methods
volume =
issue =
pages =
id =
url = http://linkinghub.elsevier.com/retrieve/pii/S0165-0270(06)00113-0
doi = 10.1016/j.jneumeth.2006.02.003

*cite journal
author = Gerriets, T., F. Li, M. D. Silva, X. Meng, M. Brevard, C. H. Sotak, M. Fisher
year = 2003
month =
title = The macrosphere model: evaluation of a new stroke model for permanent middle cerebral artery occlusion in rats
journal = J Neurosci Methods
volume = 122
issue =
pages = 201–11
id =
url = http://linkinghub.elsevier.com/retrieve/pii/S0165027002003229
doi = 10.1016/S0165-0270(02)00322-9

*cite journal
author = Gerriets, T., E. Stolz, M. Walberer, C. Muller, C. Rottger, A. Kluge, M. Kaps, M. Fisher, G. Bachmann
year = 2004
month =
title = Complications and Pitfalls in Rat Stroke Models for Middle Cerebral Artery Occlusion: A Comparison Between the Suture and the Macrosphere Model Using Magnetic Resonance Angiography
journal = Stroke
volume = 35
issue =
pages = 2372–2377
id =
url = http://www.strokeaha.org/cgi/content/abstract/35/10/2372
doi = 10.1161/01.STR.0000142134.37512.a7

*cite journal
author = Graham,S.M, McCullough, L.D, Murphy, S.J
year = 2004
title =Animal Models of Ischemic Stroke: Balancing Experimental Aims and Animal Care
journal = Comp Med
volume = 54
pages = 486–496
url = http://www.aalas.org/pdfUtility.aspx?pdf=CM/54_05_02.pdf

*cite journal
author = Koizumi, J., Y. Yoshida, T. Nakazawa, G. Ooneda
year = 1986
month =
title = 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
journal = Jpn J Stroke
volume = 8
issue =
pages = 1–8
id =
url =

*cite journal
author = Longa, E. Z., P. R. Weinstein, S. Carlson, R. Cummins
year = 1989
month =
title = Reversible middle cerebral artery occlusion without craniectomy in rats
journal = Stroke
volume = 20
issue =
pages = 84–91
id =
url = http://stroke.ahajournals.org/cgi/content/abstract/20/1/84
pmid = 2643202

*cite journal
author = Mayzel-Oreg, O., T. Omae, M. Kazemi, F. Li, M. Fisher, Y. Cohen, C. H. Sotak
year = 2004
month =
title = Microsphere-induced embolic stroke: an MRI study
journal = Magn Reson Med
volume = 51
issue =
pages = 1232–8
id =
url = http://doi.wiley.com/10.1002/mrm.20100
doi = 10.1002/mrm.20100

*cite journal
author = Schmid-Elsaesser, R., S. Zausinger, E. Hungerhuber, A. Baethmann, H. J. Reulen
year = 1989
month =
title = 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
journal = Stroke
volume = 29
issue =
pages = 2162–70
id =
url = http://stroke.ahajournals.org/cgi/content/abstract/29/10/2162
pmid = 9756599

*cite journal
author = Tamura, A., D. I. Graham, J. McCulloch, G. M. Teasdale
year = 1981
month =
title = Focal cerebral ischaemia in the rat: 1. Description of technique and early neuropathological consequences following middle cerebral artery occlusion
journal = J Cereb Blood Flow Metab
volume = 1
issue =
pages = 53–60
id =
url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7328138&dopt=Abstract

*cite journal
author = Watson, B. D., W. D. Dietrich, R. Busto, M. S. Wachtel, M. D. Ginsberg
year = 1985
month =
title = Induction of reproducible brain infarction by photochemically initiated thrombosis
journal = Ann Neurol
volume = 17
issue =
pages = 497–504
id =
doi = 10.1002/ana.410170513

*cite journal
author = Zhang, Z., R. L. Zhang, Q. Jiang, S. B. Raman, L. Cantwell, M. Chopp
year = 1997
month =
title = A new rat model of thrombotic focal cerebral ischemia
journal = J Cereb Blood Flow Metab
volume = 17
issue =
pages = 123–35
id =
doi = 10.1097/00004647-199702000-00001


Wikimedia Foundation. 2010.

Игры ⚽ Нужна курсовая?

Look at other dictionaries:

  • Animal models of stroke — are procedures undertaken in animals (including non human primates) intending to provoke pathophysiological states that are similar to those of human stroke to study basic processes or potential therapeutic interventions in this disease. Aim is… …   Wikipedia

  • Animal model — An animal model is a living, non human animal used during the research and investigation of human disease, for the purpose of better understanding the disease without the added risk of causing harm to an actual human being during the process. The …   Wikipedia

  • Neonatal stroke — is defined as a disturbance to the blood supply of the developing brain in the first 28 days of life.[1] This description includes both ischemic events, which results from the disruption of arteries, and hemorrhagic events, which results from the …   Wikipedia

  • Ocular ischemic syndrome — Classification and external resources ICD 10 H34 DiseasesDB 34069 …   Wikipedia

  • Spontaneously hypertensive rat — (SHR) is an animal model of essential (or primary) hypertension, used to study cardiovascular disease. It is the most studied model of hypertension measured as number of publications ref|pinto1998. The SHR strain was obtained during the 1960s by… …   Wikipedia

  • Rose bengal — Chembox new ImageFile = rosebengalskeletal.png ImageSize = IUPACName = 4,5,6,7 Tetrachloro 3 ,6 dihydroxy 2 ,4 ,5 ,7 tetraiodo 3 H spiro [isobenzofuran 1,9 xanthen] 3 one OtherNames = C.I. 45440 Section1 = Chembox Identifiers CASNo = 11121 48 5… …   Wikipedia

  • Protective autoimmunity — is a condition in which cells of the adaptive immune system contribute to maintenance of the functional integrity of a tissue, or facilitate its repair following an insult. The term ‘protective autoimmunity’ was coined by Prof. Michal Schwartz of …   Wikipedia

  • Therapeutic hypothermia — This article is about deliberately induced cooling. For the adverse condition of Hypothermia, see Hypothermia. Therapeutic hypothermia Intervention ICD 10 PCS 6A4 OPS 301 code …   Wikipedia

  • Neuroplasticity — Contrary to common ideas as expressed in this diagram, brain functions are not confined to certain fixed locations. Neuroplasticity is a non specific neuroscience term referring to the ability of the brain and nervous system in all species to… …   Wikipedia

  • Glutamate carboxypeptidase II — Reaction Scheme of NAAG Degradation by GCPII: GCPII + NAAG → GCPII NAAG complex → Glutamate + NAA Identifiers EC number …   Wikipedia

Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”