Q1: How does the sodium laurate model specifically mimic lacunar infarcts, distinguishing it from other stroke models?

This model uniquely induces selective occlusion of the perforating arteries, which are the small, deep vessels typically affected in human lacunar infarcts. Unlike models that cause global ischemia or large vessel occlusion, the sodium laurate method creates localized microthrombi containing fibrin, closely replicating the pathology seen in these specific clinical presentations. This targeted approach provides a more accurate representation of the underlying vascular pathology in lacunar stroke.

Q2: What are the primary mechanisms of injury induced by sodium laurate in the cerebral microvasculature?

Sodium laurate primarily causes direct damage to the endothelial cells lining the microvessels, leading to their exfoliation. This initial injury triggers rapid platelet adhesion and aggregation, culminating in the formation of occlusive microthrombi. Subsequently, this vascular disruption results in blood-brain barrier breakdown, localized ischemia, and a robust inflammatory response, all contributing to neuronal dysfunction and infarction.

Q3: Can this model be used to evaluate chronic effects or long-term therapeutic interventions?

While the acute phase of injury and immediate neurological deficits are well-characterized, the model can certainly be adapted for chronic studies. By assessing long-term behavioral outcomes, persistent inflammation, and neuronal degeneration over weeks or months, researchers can evaluate the sustained efficacy of therapeutic interventions aimed at preventing chronic neurological impairments or promoting long-term recovery.

Q4: Is it possible to control the size or location of the cerebral infarcts induced by sodium laurate?

The total size of the cerebral infarcts induced by sodium laurate is comparatively constant and highly reproducible with a standardized dose and administration method. However, the exact distribution of individual small infarcts can be somewhat unpredictable. Our experienced team employs meticulous surgical techniques and consistent protocols to maximize reproducibility and minimize variability across study animals.

Q5: Can the sodium laurate model be combined with other disease models or genetic backgrounds?

Yes, the sodium laurate model's targeted nature makes it suitable for combination studies. It can be integrated with models of other neurological conditions, such as those involving amyloid pathology or hypertension, to investigate the complex interplay between different disease mechanisms. This allows for a more nuanced understanding of co-morbidities and the development of multi-target therapies.

Q6: What are the advantages of using a repetitive injection strategy in this model?

A repetitive injection strategy, such as administering sodium laurate on multiple days, allows for the induction of a progressive neurological deficit. This approach more closely mimics the gradual clinical progression observed in some patients with lacunar infarction, providing a valuable tool for evaluating therapies designed to halt or reverse disease progression over time.

Sodium Laurate induced Cerebral Microvascular Injury Modeling & Pharmacodynamics Service

Introduction

Stroke, a leading cause of long-term disability and mortality worldwide, encompasses a spectrum of cerebrovascular events. Among these, cerebral microvascular injury (CMVI) plays a pivotal role in various neurological conditions, including ischemic stroke, vascular dementia, and neurodegenerative diseases. Understanding and mitigating CMVI is crucial for developing effective therapies.

Creative Biolabs is dedicated to advancing stroke research, offering a comprehensive suite of well-established preclinical models to rigorously evaluate the efficacy of novel therapeutic compounds.

Sodium Laurate-Induced Cerebral Microvascular Injury Model

The sodium laurate-induced cerebral microvascular injury model provides a highly relevant and reproducible platform for investigating the pathophysiology of small vessel disease and lacunar infarcts. This model precisely mimics the thrombotic occlusion of perforating arteries, a hallmark of these conditions, leading to localized cerebral infarcts and observable neurological deficits. It is particularly valuable for studying endothelial damage, microthrombus formation, blood-brain barrier disruption, and subsequent neuroinflammation.

Model Construction Steps

The construction of this model involves a precise surgical procedure to deliver sodium laurate directly into the cerebral vasculature, ensuring targeted microvascular injury.

01Anesthesia and Positioning

Male rats are anesthetized with sodium pentobarbital and positioned supine for surgical access.

02Vascular Exposure

A longitudinal incision is made in the cervical skin to expose the left common, external, and internal carotid arteries.

03Ligation and Catheterization

The left external carotid, occipital, and pterygopalatine arteries are ligated. A polyethylene catheter is then carefully inserted into the external carotid artery, with its tip positioned near the carotid bifurcation.

04Sodium Laurate Injection

The common carotid artery is temporarily clamped. 100 μg of sodium laurate, dissolved in saline, is slowly injected into the internal carotid artery over 30 seconds.

05Catheter Removal and Ligation

Following the injection, the catheter is removed, and the external carotid artery is ligated slightly proximal to the injection site.

06Repetitive Insult (Optional)

For progressive neurological deficits, a second injection of 100 μg sodium laurate can be administered into the internal carotid artery 48 hours after the first, following re-exposure of the common carotid artery.

Strengths and Limitations

Strengths:

High Reproducibility: Consistent lesion size and pathological outcomes due to precise, localized injury induction.
Targeted Microvascular Damage: Selectively induces injury in perforating arteries, mirroring human lacunar infarcts, unlike global ischemia models.
Fibrin-Containing Thrombi: Formation of clinically relevant microthrombi composed of platelets, fibrin, leukocytes, and erythrocytes.
Mimics Progressive Deficits: Repetitive injections can reproduce the gradual neurological deterioration seen in some clinical cases.

Limitations:

Unpredictable Infarct Distribution: While total infarct size is consistent, the exact location of individual small infarcts can vary.
Acute Treatment Focus: Initial studies often involve very early therapeutic intervention, necessitating further research into delayed treatment effects.
Dose Sensitivity: Higher doses of sodium laurate can lead to severe, potentially fatal, systemic effects, requiring careful dose optimization.

Evaluation Platform

Creative Biolabs offers a robust and comprehensive evaluation platform to thoroughly characterize the Sodium Laurate-induced CMVI model and assess therapeutic efficacy. Our state-of-the-art facilities enable detailed biochemical, molecular, cellular, histopathological, behavioral, and advanced imaging analyses, providing a holistic understanding of disease progression and treatment outcomes.

Test Indicators:

Histopathological Analysis: Infarct volume/area, microthrombus quantification (Phosphotungstic Acid Hematoxylin - PTAH staining), endothelial integrity (electron microscopy), neuronal damage, glial activation (GFAP, Iba1 immunohistochemistry).
Neurological Deficit Scoring: Posture reflex test, modified neurological severity scores (mNSS).
Blood-Brain Barrier Integrity: Evans Blue extravasation, immunohistochemistry for tight junction proteins (e.g., ZO-1, Occludin, Claudin-5).
Biochemical Markers: Inflammatory cytokines (e.g., TNF-α, IL-1β, IL-6), oxidative stress markers (e.g., MDA, SOD activity).
Behavioral Assessments: Cognitive function tests (e.g., Y-maze, Morris Water Maze for long-term studies), motor coordination tests.
Imaging: MRI (T2-weighted imaging for infarcts, diffusion-weighted imaging for acute ischemia, perfusion imaging).

Applications

Disease Simulation: Accurately simulating key aspects of human cerebrovascular conditions, including lacunar infarcts, small vessel disease, vascular dementia, and microthrombotic components of ischemic stroke, enabling a deeper understanding of their pathophysiology.
Drug Evaluation: Providing a reliable platform for the preclinical assessment of a diverse range of therapeutic agents, such as neuroprotective compounds, anti-inflammatory drugs, thrombolytics, and modulators of blood-brain barrier integrity or cerebral blood flow.
Treatment Development: Facilitating the development and optimization of novel treatment strategies for acute ischemic stroke (including delayed intervention paradigms), chronic cerebrovascular diseases, and interventions aimed at preventing secondary brain injury following microvascular insult.

Related Stroke Models

Our Advantages

Customized Study Design: Flexible protocols tailored precisely to your unique research objectives and compound characteristics.
Comprehensive Analytical Capabilities: Access to a full spectrum of advanced histological, biochemical, behavioral, and imaging techniques.
Translational Relevance: Models designed to provide data highly predictive of clinical outcomes, accelerating your drug development pipeline.
Rigorous Quality Standards: Commitment to reproducible results and, when required, GLP-compliant studies for regulatory submission.
Dedicated Scientific Support: Collaborative partnership with our expert team from study inception to data interpretation.

Work with Us

Inquiry Stage

Summarize the project requirements and fill in the information collection form.
Sign a CDA from both parties to further communicate information, such as targets.
Select an animal model, discuss experimental design, and determine assay parameters.
Project costing and project schedule forecasting.

Project Start

We provide a detailed project plan, including the required sample quantities, methods, and protocols.
Both parties confirm the project details and start the project.
Confirm the timeline of the project.

Project Progress

We provide periodic results and information on the animal's condition.
We will work together to make project adjustments as necessary.

Project Completion

We provide a comprehensive project report promptly.
We arrange transportation for the produced samples.
We provide a discussion of the project results and help to arrange the next steps.

After-Sales Support

Data storage and archiving.

Contact Us

Creative Biolabs stands ready to empower your research into cerebral microvascular injury. By leveraging our expertise and the robust Sodium Laurate-induced CMVI model, we offer comprehensive services designed to accelerate your drug discovery and development efforts. Contact us today to discuss your project requirements and explore how we can support your scientific endeavors.

FAQs

Q1: How does the sodium laurate model specifically mimic lacunar infarcts, distinguishing it from other stroke models?

A: This model uniquely induces selective occlusion of the perforating arteries, which are the small, deep vessels typically affected in human lacunar infarcts. Unlike models that cause global ischemia or large vessel occlusion, the sodium laurate method creates localized microthrombi containing fibrin, closely replicating the pathology seen in these specific clinical presentations. This targeted approach provides a more accurate representation of the underlying vascular pathology in lacunar stroke.
Q2: What are the primary mechanisms of injury induced by sodium laurate in the cerebral microvasculature?

A: Sodium laurate primarily causes direct damage to the endothelial cells lining the microvessels, leading to their exfoliation. This initial injury triggers rapid platelet adhesion and aggregation, culminating in the formation of occlusive microthrombi. Subsequently, this vascular disruption results in blood-brain barrier breakdown, localized ischemia, and a robust inflammatory response, all contributing to neuronal dysfunction and infarction.
Q3: Can this model be used to evaluate chronic effects or long-term therapeutic interventions?

A: While the acute phase of injury and immediate neurological deficits are well-characterized, the model can certainly be adapted for chronic studies. By assessing long-term behavioral outcomes, persistent inflammation, and neuronal degeneration over weeks or months, researchers can evaluate the sustained efficacy of therapeutic interventions aimed at preventing chronic neurological impairments or promoting long-term recovery.
Q4: Is it possible to control the size or location of the cerebral infarcts induced by sodium laurate?

A: The total size of the cerebral infarcts induced by sodium laurate is comparatively constant and highly reproducible with a standardized dose and administration method. However, the exact distribution of individual small infarcts can be somewhat unpredictable. Our experienced team employs meticulous surgical techniques and consistent protocols to maximize reproducibility and minimize variability across study animals.
Q5: Can the sodium laurate model be combined with other disease models or genetic backgrounds?

A: Yes, the sodium laurate model's targeted nature makes it suitable for combination studies. It can be integrated with models of other neurological conditions, such as those involving amyloid pathology or hypertension, to investigate the complex interplay between different disease mechanisms. This allows for a more nuanced understanding of co-morbidities and the development of multi-target therapies.
Q6: What are the advantages of using a repetitive injection strategy in this model?

A: A repetitive injection strategy, such as administering sodium laurate on multiple days, allows for the induction of a progressive neurological deficit. This approach more closely mimics the gradual clinical progression observed in some patients with lacunar infarction, providing a valuable tool for evaluating therapies designed to halt or reverse disease progression over time.

Published Data

A seminal study demonstrated the successful development of this model in rats, showing selective microthrombotic occlusion of perforating arteries leading to cerebral infarcts and neurological deficits. Their research further highlighted the neuroprotective effect of a rho-kinase inhibitor, in this model, significantly improving neurological outcomes and reducing infarct area. This study underscores the model's utility for investigating pathophysiology and evaluating potential therapies for lacunar infarcts.

For Research Use Only.

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