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A Thrombotic Stroke Model Based On Transient Cerebral Hypoxia-ischemia
Published on: August 18, 2015
Experimental thromboembolic stroke in cynomolgus monkey
G Kito1, A Nishimura, T Susumu
1Shin Nippon Biomedical Laboratories (SNBL) Ltd., 2438 Miyanoura, Yoshida, 891-1394, Kagoshima, Japan. kito@snbl.co.jp
Abstract:
To develop an experimental model of thromboembolic stroke without intracranial surgery, an autologous blood clot was delivered to the middle cerebral artery (MCA) via the internal carotid artery in cynomolgus monkeys. Male cynomolgus monkeys, in which a chronic catheter had been earlier implanted in the left internal carotid artery, were used. The clot was flushed into the internal carotid artery under sevofluorane anesthesia. A neurologic deficit score was assigned after MCA embolization. After 24 h, cerebral infarct size and location were determined by the TTC staining method. Cerebral blood flow (CBF) was measured prior to and after MCA embolization, using positron emission tomography (PET). After embolization, long-lasting and profound extensor hypotonia of the contralateral upper and lower limbs, and mild to severe incoordination were observed. Contralateral hemiplegia was observed over the following 24 h. In gross morphologic observation of the brain, the lesions involved mostly the caudate nucleus, putamen, globus pallidus and insular cortex. CBF was maximally reduced in the left MCA territory, but not in the right MCA territory. This model is relevant to thromboembolic stroke in human in neurologic dysfunction and histopathologic brain damage.
Insights
Researchers developed a new experimental model for thromboembolic stroke using cynomolgus monkeys. This model accurately replicates human stroke symptoms and brain damage without invasive intracranial surgery.
Area of Science:
- Neuroscience
- Cerebrovascular Research
- Primate Models
Background:
- Thromboembolic stroke is a leading cause of disability.
- Current experimental models often require invasive intracranial surgery.
- A non-surgical, reproducible model is needed for stroke research.
Purpose of the Study:
- To establish a novel experimental model of thromboembolic stroke.
- To induce stroke by embolizing the middle cerebral artery (MCA) in non-human primates.
- To characterize the resulting neurological deficits and histopathological changes.
Main Methods:
- Autologous blood clots were delivered to the MCA via the internal carotid artery in male cynomolgus monkeys.
- Neurological deficit scores were assessed post-embolization.
- Cerebral infarcts were quantified using 2,3,5-triphenyltetrazolium chloride (TTC) staining.
- Cerebral blood flow (CBF) was measured using positron emission tomography (PET).
Main Results:
- Embolization induced contralateral hemiplegia, hypotonia, and incoordination.
- Histopathology revealed lesions in the caudate nucleus, putamen, globus pallidus, and insular cortex.
- PET imaging showed maximal reduction of CBF in the affected MCA territory.
Conclusions:
- This non-surgical model effectively replicates key features of human thromboembolic stroke.
- The model demonstrates significant neurological dysfunction and localized brain damage.
- It provides a valuable tool for investigating stroke pathophysiology and therapeutic interventions.
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