Middle Cerebral Artery Occlusion (MCAO) Rodent Model of Stoke & Brain Ischemia

Numerous animal models have been used to mimic clinical ischemic stroke in order to understand brain pathophysiology and to determine the efficacy of new therapies. Techniques that occlude the middle cerebral artery (MCA) and its branches, which are the cerebral vessels that are most often affected in human ischemic stroke, are closest to the disease. Among the occlusive MCA stroke models, the most widely used models produce focal lesions in the parietal cortex and striatum via transient or permanent MCAO. Creative Biolabs provides both permanent MCAO model which produces massive damage (e.g., cortex stratum, thalamic nucleus) and transient MCAO models where the artery is occluded for a period of time before reperfusion for ischemic stroke research and the development of neuroprotective agents.

Induction of MCAO Model

The induction of MCAO model involves temporarily occluding the common carotid artery (CCA), introducing a suture into the internal carotid artery (ICA) or the transected external carotid artery (ECA), and advancing the suture until it interrupts the blood supply to the MCA. Occlusion of the middle cerebral artery (MCA) leads to a reduction of cerebral blood flow in both the striatum and the cortex, but the degree largely depends on the duration and site of the occlusion. The most common durations of transient MCAO using a suture are 60 minutes, 90 minutes, and 120 minutes in rats. No ischemic lesions are observed in mice subjected to MCAO below or equal to 10 minutes, whereas an MCAO of 15 minutes leads to a detectable infarction. Laser Doppler flowmetry can be a useful tool for ensuring complete MCAO.

MCAO models of stroke and brain ischemia available for use in our studies include:

• Permanent MCAO Rat Model
• Transient MCAO Rat Model
• Transient MCAO Mouse Model

Fig.1 Scheme of an intraluminal suture MCAO model and different methods for determining infarct volume. (A) Diagram of MCAO. (B) Representative of 2,3,5-triphenyl tetrazolium chloride staining of three consecutive coronal brain sections after transient MCAO. (C) Serial coronal T2-weighted gradient echo magnetic resonance images after transient MCAO. (D) Representative hematoxylin and eosin (top) and Nissl staining (bottom) of coronal brain sections after transient MCAO. (Fluri et al. 2015)

Features of MCAO Model

• This model mimics human ischemic stroke in the origination and exhibits a penumbra that is similar to that of human stroke.
• The MCAO model is characterized by large infarct volumes and high reproducibility.
• The reperfusion and the duration of ischemia are precisely controllable.
• It is less invasive and does not require craniectomy and thus avoids damage to cranial structures.
• It is considered to be suitable for reproducing ischemic stroke and subsequent neuronal cell death, cerebral inflammation, and blood-brain barrier (BBB) damage, as well as producing good results in behavior tests.
• This technique may lead to inadequate MCAO or may be followed by vessel rupture and subsequent subarachnoid hemorrhage (SAH), but these shortcomings can be solved by using a silicone-coated suture and laser Doppler-guided placement of the suture.

Assessments

Our preclinical service section offers an array of behavioral tests, functional recovery test, and histological assessments to assess the potential effect of novel therapeutics, including but not limited to:

• Behavioral tests (e.g., motor function, cognition, social behavior)
• Cerebral blood-flow and vessels imaging (transcranial laser Doppler)
• Infarct volume measurement (magnetic resonance imaging (MRI), tetrazolium chloride (TTC))
• Histology

Creative Biolabs also offers other stroke and brain ischemia rodent models that you may be interested in:

• Endothelin-1 Model
• Photothrombotic Ischemia Model
• Global Ischemic Four-Vessel Occlusion (4-VO) Rat Model

The comprehensive list of rodent neurological disease models is placed below for your review. Please click the links for more detailed description of each model:

With years of experience with preclinical efficacy studies, Creative Biolabs is a good research partner to help guide your decision regarding the most suitable model for your research needs. We can develop customized study designs and protocols that exactly meet our clients' needs. Contact us for more information on the above models or if you would like to propose a new model.

Reference

1. Fluri, F.; et al. Animal models of ischemic stroke and their application in clinical research[J]. Drug Design Development & Therapy. 2015, 9(default):3445.

For Research Use Only.