Sep 24, 2024 Leave a message

Advancing Bleeding And Clotting Therapeutic Innovations With Cynomolgus Monkey MCAO Model

Stroke, also known as cerebrovascular accident (CVA), is an acute brain dysfunction caused by either an obstruction or rupture of cerebral circulation. There are two main types of strokes: ischemic and hemorrhagic. Among these, ischemic stroke, which results from reduced blood flow due to thrombosis or embolism, is the more common type. Stroke remains one of the leading causes of death and disability worldwide, posing a significant challenge and burden to public health.

Comparing T2-weighted MRI Imaging in Humans, Cynomolgus Monkeys, and Rats
Comparing T2-weighted MRI Imaging in Humans, Cynomolgus Monkeys, and Rats


A successful animal model can simulate the pathological processes of human diseases, providing researchers with a vital tool to explore disease progression and assess therapeutic efficacy. Due to its high genetic, anatomical, and physiological similarities to humans, the cynomolgus monkey has become an ideal animal model for neuroscience and stroke research. Compared to more commonly used small animal models like rats or mice, the brain structure of monkeys more closely resembles that of humans, particularly in the proportion of the cortex and white matter. This enables a more accurate reflection of human disease progression and treatment responses. Additionally, the larger body size of monkeys allows for more precise real-time imaging, surgical procedures, and drug interventions, ensuring greater accuracy and control in research. Therefore, the cynomolgus monkey model offers irreplaceable advantages in simulating complex human diseases.

 

 

Prisys Biotech's MCAO Model


Prisys Biotech's Middle Cerebral Artery Occlusion (MCAO) model is an effective animal model for simulating ischemic stroke. By precisely controlling the occlusion site and duration, this model accurately replicates the pathological processes of human stroke, providing a crucial tool for studying stroke mechanisms and potential therapeutic strategies.

An Optimal Animal Model of Ischemic Stroke Established by Digital Subtraction Angiography-Guided Autologous Thrombi in Cynomolgus Monkeys

DSA-guided cerebral angiography and real-time imaging of MCAO in cynomolgus macaque
DSA-guided cerebral angiography and real-time imaging of MCAO in cynomolgus macaque

 

 

Currently, Prisys Biotech has established a mature cynomolgus monkey MCAO model . Data related to this model have been published in the journal Frontiers in Neurology, and the model has successfully supported the preclinical efficacy evaluation of several new drugs.

 

 

Key Clinical Endpoints

 

  • Vascular Reperfusion: Evaluated using CTA, MRA, and CTP imaging to assess vascular recanalization.
  • Ischemic Changes in Brain Tissue: Acute brain ischemia areas are observed using MRI and DWI sequences.
  • Behavioral Outcomes: Neurological deficit scores are recorded for 7 consecutive days post-surgery, focusing on consciousness, motor function, and coordination.
  • Brain Tissue Staining: TTC staining is used to detect infarct areas, assessing the extent and severity of brain damage.
Summary of CT Images Comparing Two MCAO Model Groups
Summary of CT Images Comparing Two MCAO Model Groups
In the experimental group, CTA scans conducted at 24 hours and on day 7 post-surgery showed reperfusion in the MCA and its distal branches, while no visualization of the MCA was observed in the control group. Significant differences were noted in CTP scans between the two groups (indicated by white arrows).

 

 

Model Advantages

 

  • High Clinical Relevance: The model uses autologous venous thrombi to induce MCA occlusion, simulating the most common type of ischemic stroke seen in clinical settings, thereby closely reflecting the pathogenesis and therapeutic responses in human stroke.
  • Minimally Invasive Procedure: Vascular catheterization under DSA guidance ensures accurate thrombus placement with minimal surgical trauma, reducing postoperative complications and improving the reliability of experimental results.
  • High Reproducibility and Stability: The model demonstrates a high success rate, providing consistent outcomes and a stable foundation for subsequent experimental research.
  • Comprehensive Imaging Evaluation: Multi-dimensional real-time monitoring using CTA, CTP, and MRI offers clear and precise assessments of vascular recanalization and ischemic damage to brain tissue.
  • Low Mortality Rate: The minimally invasive procedure causes less trauma, ensuring the safety of the animals during surgery. Adherence to clinical care standards improves survival rates, making the model suitable for long-term research.
  • Ultra-acute Phase Dose Evaluation: This model allows for the evaluation of drug dosage and efficacy during the ultra-acute phase following stroke onset.

 

Neurological Deficit Scores on Day 7 Post-Surgery
Neurological Deficit Scores on Day 7 Post-Surgery. After 7 days of thrombolytic therapy, the neurological deficit scores in the experimental group showed a significant decrease compared to the control group. Data are presented as mean ± standard deviation. The vertical axis represents the neurological deficit score, and the horizontal axis represents time post-infarction.

 

 

Expanding into Hemorrhage and Coagulation Disease Models

 


In addition to its leading-edge expertise in central nervous system  and ischemic stroke models, Prisys Biotech also focuses on studying blood-related disorders, particularly in the fields of hemorrhagic and thrombotic diseases. Our bleeding and clotting disease models  encompass a range of common and rare pathological conditions, including Hemophilia A, A-V Shunt, Intracerebral Hemorrhagic Stroke, and more. These models provide a reliable experimental platform for researching the underlying mechanisms of these diseases and developing new therapeutic approaches, further cementing Prisys Biotech's professional standing in preclinical large-animal pharmacology studies.

 


Prisys Biotech remains committed to pioneering innovative research methods to address the global challenges posed by stroke and related diseases. We will continue to strengthen collaborations with industry partners to accelerate the clinical translation of research findings and ultimately deliver more effective treatment options for patients.

 

References
Ye J, Shang H, Du H, et al. An Optimal Animal Model of Ischemic Stroke Established by Digital Subtraction Angiography-Guided Autologous Thrombi in Cynomolgus Monkeys. Frontiers in Neurology. 2022;13:864954. doi:10.3389/fneur.2022.864954.

 

 

About Prisys Biotech

 

Prisys Biotechnologies Co., Ltd. is accredited by AAALAC, specializing in preclinical and translational drug evaluations and new drug technology development. Focusing on large animal pharmacology and efficacy studies, Prisys Biotech offers a range of services, including disease models, pharmacodynamics, safety evaluation, biomarker research, and mechanism validation using non-human primates such as cynomolgus monkeys. Prisys Biotech has established a translational medicine center that meets pharmaceutical industry standards and has formed long-term partnerships with top pharmaceutical companies, biotech firms, and academic institutions worldwide.

DSA Digital Subtraction Angiography of Prisys Biotech

 

 

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