Q1: How does the collagenase-induced ICH model differ from other common ICH models, such as the autologous blood injection model?

The collagenase model distinguishes itself by inducing a more gradual and progressive hemorrhage, closely mimicking the spontaneous bleeding often seen in human ICH. In contrast, the autologous blood injection model involves an immediate bolus of blood, which may not fully replicate the dynamic vascular damage and hematoma expansion observed clinically. This difference makes the collagenase model particularly valuable for studying therapies targeting the evolving injury cascade.

Q2: What specific brain regions can be targeted for collagenase injection, and how does the choice of region impact the study?

Common target regions include the striatum and cortex. Injecting into the striatum typically results in more severe motor deficits due to its critical role in movement control, while cortical injections can lead to sensory or cognitive impairments. The choice of brain region is crucial and depends on the specific neurological deficits or pathological processes your research aims to investigate.

Q3: What are the key secondary injury mechanisms that this model effectively recapitulates, and why are they important for therapeutic development?

The model faithfully reproduces critical secondary injuries such as perihematomal edema, neuroinflammation, BBB disruption, and oxidative stress. These mechanisms are vital because they significantly contribute to neuronal damage and functional deficits after the initial bleed. Therapies targeting these pathways are crucial for improving patient outcomes, and this model provides an excellent platform for their evaluation.

Q4: Can this model be used to assess long-term neurological functional recovery, beyond acute injury?

Absolutely. The collagenase-induced ICH model is well-suited for long-term studies. We can track functional recovery over weeks or even months post-injury using a battery of behavioral tests. This allows for the evaluation of therapies that aim not just to mitigate acute damage but also to promote sustained neurological improvement and rehabilitation.

Q5: Is the collagenase-induced ICH model suitable for GLP compliant studies?

Yes, our facilities and protocols are designed to support GLP-compliant studies. We understand the stringent requirements for regulatory submissions and ensure that all aspects of the study, from animal housing and husbandry to data collection and analysis, adhere to GLP principles. This provides clients with high-quality, auditable data suitable for IND applications.

Collagenase induced Hemorrhagic Stroke Modeling & Pharmacodynamics Service

Introduction

Stroke remains a leading cause of long-term disability and mortality worldwide, with intracerebral hemorrhage (ICH) representing a particularly severe subtype. Characterized by bleeding directly into the brain tissue, ICH often leads to significant neurological deficits and a high fatality rate, underscoring an urgent need for effective therapies.

At Creative Biolabs, we are dedicated to advancing stroke research by providing a comprehensive suite of well-established and clinically relevant preclinical models, enabling precise evaluation of novel therapeutic strategies.

Collagenase-Induced Hemorrhagic Stroke Model

The collagenase-induced hemorrhagic stroke model is a widely recognized and highly translational preclinical model for studying ICH. It is designed to mimic the spontaneous, non-traumatic bleeding characteristic of human ICH, allowing researchers to investigate the intricate cascade of primary and secondary brain injuries.

Schematic representation of stroke animal model. (OA Literature) Fig.1 Illustration of induced hemorrhagic stroke model.¹

Model Construction Steps

The construction of the collagenase-induced ICH model involves the precise stereotaxic delivery of bacterial collagenase into a specific brain region, leading to a controlled and gradual extravasation of blood. This method ensures a reproducible and clinically relevant hemorrhage.

01Animal Preparation

Rodents (typically rats or mice) are anesthetized and securely positioned in a stereotaxic frame to ensure precise targeting.

02Targeted Brain Region Selection

A small burr hole is made in the skull, and a micro-syringe is carefully lowered into a predetermined brain region, commonly the striatum or cortex, based on the study's objectives.

03Collagenase Preparation

A precise concentration of bacterial collagenase (e.g., Type IV or VII) is prepared in a sterile saline solution.

04Stereotaxic Injection

The collagenase solution is slowly infused into the target brain region over several minutes, allowing for gradual enzymatic degradation of vascular basement membranes and subsequent blood vessel rupture.

05Post-operative Care

After needle withdrawal and skull closure, animals receive appropriate post-operative care, including analgesia and monitoring, to ensure recovery and minimize distress.

Strengths and Limitations

Strengths:

Mimics Spontaneous Bleeding: Replicates the gradual, ongoing bleeding seen in human ICH, unlike models involving direct blood injection.
Reproducible Hematoma: Offers highly consistent hematoma volumes through precise control of collagenase concentration and injection parameters.
Recapitulates Secondary Injuries: Faithfully reproduces critical post-ICH pathologies, including perihematomal edema, neuroinflammation, oxidative stress, and significant blood-brain barrier (BBB) disruption.
Translational Relevance: Its consistent pathological features and progressive injury profile make it highly suitable for evaluating novel therapeutic agents.
Long-Term Functional Assessment: Allows for comprehensive evaluation of persistent behavioral deficits and recovery trajectories over extended periods.

Limitations:

Variability in Hematoma Evolution: Despite efforts for reproducibility, slight variations in hematoma size and shape can occur due to biological variability or subtle injection differences.
Invasiveness: The stereotaxic surgical procedure is invasive, requiring careful animal handling and post-operative monitoring.

Evaluation Platform

Creative Biolabs provides a robust evaluation platform to comprehensively assess therapeutic efficacy in the collagenase-induced ICH model. Our state-of-the-art facilities and experienced scientific team enable detailed analysis across multiple domains.

Test Indicators:

Histopathological Analysis: Hematoma volume, perihematomal edema, neuronal survival, lesion size, glial activation (microglia/astrocytes).
Behavioral Assessments: Neurological Severity Scores (NSS), corner turning test, forelimb placement test, rotarod, gait analysis.
Molecular Analysis: Gene expression (qPCR), protein levels (Western blot, ELISA), inflammatory cytokines, oxidative stress markers, tight junction proteins (e.g., ZO-1, occludin), MMP-9, AQP4.
Imaging: In vivo MRI or CT for hematoma visualization and volume quantification.

Applications

Diseases Simulated: Primarily used to simulate ICH and its associated secondary brain injuries, including perihematomal edema, neuroinflammation, and neuronal death.
Drug Evaluation: Ideal for assessing neuroprotective agents, anti-inflammatory compounds, anti-edema drugs, agents targeting BBB integrity, and compounds promoting functional recovery.
Treatment Strategies: Applicable for evaluating a wide range of therapeutic interventions, including small molecules, biologics, cell-based therapies, and gene therapies.
Mechanism of Action Studies: Facilitates the elucidation of cellular and molecular pathways involved in ICH pathogenesis and the specific mechanisms by which novel therapies exert their effects.

Related Stroke Models

Our Advantages

Decades of Expertise: Years of specialized experience in preclinical neuroscience and ICH research.
Precision and Reproducibility: Meticulous execution of the collagenase model ensures consistent and reliable experimental outcomes.
Comprehensive Assessment: A full spectrum of advanced histological, behavioral, molecular, and imaging analyses.
Customized Study Design: Flexible and tailored study protocols to meet specific client research objectives.

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

Leverage Creative Biolabs' extensive experience and advanced capabilities in the collagenase-induced hemorrhagic stroke model. We provide robust preclinical services to accelerate your research and de-risk your therapeutic development programs. Contact us today to discuss your specific project needs.

FAQs

Q1: How does the collagenase-induced ICH model differ from other common ICH models, such as the autologous blood injection model?

A: The collagenase model distinguishes itself by inducing a more gradual and progressive hemorrhage, closely mimicking the spontaneous bleeding often seen in human ICH. In contrast, the autologous blood injection model involves an immediate bolus of blood, which may not fully replicate the dynamic vascular damage and hematoma expansion observed clinically. This difference makes the collagenase model particularly valuable for studying therapies targeting the evolving injury cascade.
Q2: What specific brain regions can be targeted for collagenase injection, and how does the choice of region impact the study?

A: Common target regions include the striatum and cortex. Injecting into the striatum typically results in more severe motor deficits due to its critical role in movement control, while cortical injections can lead to sensory or cognitive impairments. The choice of brain region is crucial and depends on the specific neurological deficits or pathological processes your research aims to investigate.
Q3: What are the key secondary injury mechanisms that this model effectively recapitulates, and why are they important for therapeutic development?

A: The model faithfully reproduces critical secondary injuries such as perihematomal edema, neuroinflammation, BBB disruption, and oxidative stress. These mechanisms are vital because they significantly contribute to neuronal damage and functional deficits after the initial bleed. Therapies targeting these pathways are crucial for improving patient outcomes, and this model provides an excellent platform for their evaluation.
Q4: Can this model be used to assess long-term neurological functional recovery, beyond acute injury?

A: Absolutely. The collagenase-induced ICH model is well-suited for long-term studies. We can track functional recovery over weeks or even months post-injury using a battery of behavioral tests. This allows for the evaluation of therapies that aim not just to mitigate acute damage but also to promote sustained neurological improvement and rehabilitation.
Q5: Is the collagenase-induced ICH model suitable for GLP compliant studies?

A: Yes, our facilities and protocols are designed to support GLP-compliant studies. We understand the stringent requirements for regulatory submissions and ensure that all aspects of the study, from animal housing and husbandry to data collection and analysis, adhere to GLP principles. This provides clients with high-quality, auditable data suitable for IND applications.

Published Data

The comparison of BBB breakdown between the c-ICH and the b-ICH groups. (OA Literature) Fig.2 More pronounced disruption of BBB in the collagenase-induced ICH model (c-ICH) compared to the whole blood ICH model (b-ICH).²

This study effectively demonstrated the utility of the collagenase-induced ICH model in investigating early BBB disruption and evaluating potential protective strategies. Researchers utilized the model to compare BBB integrity and associated molecular markers, such as tight junction proteins and MMP-9 activity, at early time points following hemorrhage. The project results indicated that the collagenase model exhibited a pronounced and early BBB leakage, highlighting its suitability for assessing interventions targeting this critical pathological event. This case exemplifies how the model provides crucial insights into ICH pathophysiology and therapeutic efficacy.

References

Lasica, Nebojsa et al. "Metabolomics as a potential tool for monitoring patients with aneurysmal subarachnoid hemorrhage." Frontiers in neurology vol. 13 1101524. 9 Jan. 2023. Distributed under Open Access license CC BY 4.0. The image was modified by extracting and using only part of the original image. https://doi.org/10.3389/fneur.2022.1101524
Jia, Peijun et al. "Profiling of Blood-Brain Barrier Disruption in Mouse Intracerebral Hemorrhage Models: Collagenase Injection vs. Autologous Arterial Whole Blood Infusion." Frontiers in cellular neuroscience vol. 15 699736. 26 Aug. 2021. Distributed under Open Access license CC BY 4.0, without modification. https://doi.org/10.3389/fncel.2021.699736

For Research Use Only.

Related Services:

Sodium Laurate induced Cerebral Microvascular Injury Model

tMCAO Model

NHP MCAO Model

pMCAO Model

Photochemically induced Ischemic Stroke Model

Online Inquiry