Spinal Cord Injury (SCI) – Hemisection SCI Mouse Model
Investigate your novel therapy’s potential in spinal cord regeneration using InnoSer’s clinically relevant spinal cord injury (SCI) mouse model
Spinal Cord Injury (SCI) Mouse Model Key Characteristics:
InnoSer offers specialized preclinical contract research services using a clinically relevant spinal cord injury (SCI) mouse model induced by transection. Spinal cord injury is established by means of T-cut hemisection with a partial laminectomy at thoracic level eight (T8), transecting the dorsomedial and ventral corticospinal tracts, impairing other descending and ascending tracts.
Multiple spinal cord injury model systems have been developed to test the efficacy of novel therapies. Each model allows you to study specific pathological processes and specific therapeutic mechanisms of action. Accordingly, InnoSer’s experienced spinal cord injury team is capable of running efficacy studies in different models such as contusion SCI models and laceration SCI mouse models. Additionally, InnoSer’s Spa mouse model of spasticity may represent another translationally relevant model. However, as all models have their unique characteristics, we recommend discussing your study setup in close collaboration with our experts.
✓ Standardized spinal cord damage in the SCI model is induced by T-cut hemisection combined with partial laminectomy at thoracic level eight (T8).
✓ Extensive and progressive neuroinflammation (astrocytes, microglia) and inflammatory cell activation and infiltration of peripheral immune cells).
InnoSer’s scientists have extensive experience in modeling SCI in rodent models and have published numerous papers using the transection spinal cord injury (SCI) mouse model (Erens et al., 2022). Accordingly, our staff is skilled in performing (stem) cell and medical device transplants as well as delivering (e.g., via intrathecal dosing) a range of therapeutics to evaluate the neuro–regenerative effects of your novel therapy.
InnoSer’s SCI model is a highly reproducible mouse model of spinal injury, allowing for quick set-up. Because of the immediate injury induction, immediate dosing or implantation of novel therapeutics can be performed. Therefore, the relatively short study timelines (4 weeks), can help you accelerate your preclinical spinal cord injury research.
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Spinal Cord Injury (SCI) Mouse Model Sample Data
InnoSer offers specialized preclinical contract research services using a clinically relevant spinal cord injury (SCI) mouse model.
Spinal cord injury is established using T-cut hemisection with a partial laminectomy at thoracic level eight (T8), transecting the dorso-medial and ventral corticospinal tracts, impairing other descending and ascending tracts. Consequently, the transection SCI model is characterized by severe and complete hind limb paralysis after the acute mechanical injury. Furthermore, secondary SCI occurs due to inflammation caused by excessive immune response triggered by the injury. This allows you to investigate potential treatment strategies that mitigate further spinal cord damage.
InnoSer’s spinal cord injury (SCI) mouse model induced by means of T-cut hemisection model is characterized by severe and complete hind limb paralysis after the acute mechanical injury.
T-cut hemisection in wild-type C57BL7/J mice leads to complete hind limb paralysis recorded using the Basso Mouse Scale (BMS) that gradually improves over time. BMS is a 10-point certified scale that ranges from zero to nine, indicating complete hind limb paralysis or normal locomotion, respectively. The present study investigated whether treatment with the nitric oxide synthase substrate, L-arginine, improves SCI outcomes. Compared to vehicle-treated mice, mice treated with recombinant Arginase-1 show improved functional recovery at the end of the 28-day observation period.
Figure taken with permission from Erens et al. 2022.
InnoSer’s spinal cord injury (SCI) mouse model induced by transection is suitable to test novel treatment strategies ranging from (stem) cell therapies to therapies aimed at mitigating neuroinflammation.
The present study investigated whether L-arginine depletion improves SCI outcomes related to secondary SCI-induced neuroinflammation such as microglial cell activation. Compared to vehicle-treated mice, mice treated with recombinant Arginase-1 show a similar level of neuroinflammation marked by microglial activation.
Figure taken with permission from Erens et al. 2022.
InnoSer’s spinal cord injury (SCI) mouse model induced by transection is suitable to test novel treatment strategies ranging from (stem) cell therapies to therapies aimed at mitigating neuroinflammation.
The present study investigated whether L-arginine depletion improves SCI outcomes related to secondary SCI-induced neuroinflammation such as microglial cell activation. Compared to vehicle-treated mice, mice treated with recombinant Arginase-1 show a similar level of neuroinflammation marked by microglial activation.
Figure taken with permission from Erens et al. 2022.
InnoSer’s spinal cord injury (SCI) mouse model induced by transection is suitable to test novel treatment strategies ranging from (stem) cell therapies to therapies aimed at mitigating neuroinflammation.
Microglial/Macrophage infiltration and activation are evaluated via intensity analysis of Iba-1 fluorescent images in the perilesional area of the lesion site.
InnoSer’s spinal cord injury (SCI) mouse model induced by transection is suitable to test novel treatment strategies ranging from (stem) cell therapies to therapies aimed at mitigating neuroinflammation.
The present study investigated whether L-arginine depletion improves SCI outcomes related to secondary SCI-induced neuroinflammation. Representative immunofluorescent images show significantly lower amount of cleaved caspase 3/ NeuN double positive cells (pre-apoptotic neurons) in mice treated with recombinant Arginase-1 compared to vehicle-treated mice 28 days post-injury.
Figure taken with permission from Erens et al. 2022.
InnoSer’s spinal cord injury (SCI) mouse model induced by transection is suitable to test novel treatment strategies ranging from (stem) cell therapies to therapies aimed at mitigating neuroinflammation.
The present study investigated whether L-arginine depletion improves SCI outcomes related to secondary SCI-induced neuroinflammation. Representative immunofluorescent images show infiltration of M2 and activated macrophages/microglia at the lesion site (left figure; MHCII and Arg-1) in response to recombinant Arginase-1 treatment. The right figure shows interactions between microglia/macrophages and axons. Treatment with recombinant Arginase-1 significantly reduced the number of contacts between Iba1+ and NF+ cells.
Figure taken with permission from Erens et al. 2022.
InnoSer’s spinal cord injury (SCI) mouse model induced by transection is suitable to test novel treatment strategies aimed at mitigating secondary SCI induced by peripheral cell infiltration and inflammation.
The present study investigated whether L-arginine depletion improves SCI outcomes related to secondary SCI-induced neuroinflammation such as inflammatory cell infiltration. Compared to vehicle-treated mice, mice treated recombinant Arginase-1 show significant decrease in the number of infiltrating CD4+ T cells at 28-days post SCI induction.
Figure taken with permission from Erens et al. 2022.
InnoSer’s spinal cord injury (SCI) mouse model induced by transection is suitable to test novel treatment strategies aimed at mitigating secondary SCI induced by peripheral cell infiltration and inflammation.
The present study investigated whether L-arginine depletion improves SCI outcomes related to secondary SCI-induced neuroinflammation such as inflammatory cell infiltration. Compared to vehicle-treated mice, mice treated recombinant Arginase-1 show significant decrease in the number of infiltrating CD4+ T cells at 28-days post SCI induction.
Figure taken with permission from Erens et al. 2022.
Spinal Cord Injury (SCI) Mouse Model Readouts
生物学的指標
以下の生物学的指標を用いて治療法の有効性を検証してください：
- Histopathology analyses (lesion size of the spinal cord injury, neuroinflammation, astrogliosis, microglia activation, de- and re-myelination, neuronal cell death, immune cell infiltration)
- Blood collection for PK/PD profiling
- CSF collection
- Biomarker analyses (qPCR, MSD, ELISA, Western blot)
- Peripheral immune cell response profiling (flow cytometry)
- Complementary in vitro assays (in vitro mouse and human immune cell activation and polarization assays, scratch assay, viability assay)
当チームの注目出版物
- Erens, C., Van Broeckhoven, J., Hoeks, C., Schabbauer, G., Cheng, P. N., Chen, L., Hellings, N., Broux, B., Lemmens, S., & Hendrix, S. (2022). L-Arginine Depletion Improves Spinal Cord Injury via Immunomodulation and Nitric Oxide Reduction. Biomedicines, 10(2), 205. https://doi.org/10.3390/biomedicines10020205
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主任神経科学研究員
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主任神経科学研究員
よくあるご質問
What is a SCI mouse model?
A Spinal Cord Injury (SCI) mouse model is a preclinical research tool designed to study the mechanisms, progression, and novel treatments of spinal cord injuries. These models replicate human SCI conditions, allowing you to evaluate the efficacy of your novel therapeutic interventions.
Common SCI mouse models include:
- Contusion and compression SCI models: Mimic the biomechanics and pathology of human injuries.
- Hemisection SCI models: Useful for studying specific functional recovery mechanisms.
- Transection SCI models: Valuable for examining anatomic regeneration.
The choice of a model depends on your study objectives, as each model provides distinct insights. Discuss with our team which SCI mouse model is best suited for your research.
How do you induce a T-cut hemisection?
A T-cut hemisection is induced through a precise surgical procedure. First, mice undergo a partial laminectomy at thoracic level eight (T8) to expose the spinal cord. Using iridectomy scissors, a bilateral hemisection is then performed, transecting both the dorsomedial corticospinal tract and the ventral corticospinal tract. Once the hemisection is complete, the muscles are carefully sutured, and the skin is closed using wound clips to ensure proper healing.
This method creates a controlled spinal cord injury, making it an effective model for studying recovery mechanisms and evaluating therapeutic interventions. Continue reading more about the methodology to include T-cut hemisection in the publication by Erens et al., (2022).
Are there profound differences between a contusion and hemisection model?
Contusion mouse model of SCI is induced by either the weight-drop or impactor methods whereas the hemisection mouse model of SCI induces mimics spinal cord damage by inducing a surgical lesion. Contusion and hemisection SCI models differ in several critical aspects:
- Lesion severity: Hemisection models typically produce more controlled injuries, while contusion models result in more variable damage.
- Readout options: Functional readouts such as CatWalk gait analysis may not be feasible in hemisection models.
- Scar tissue formation: Hemisection models often generate less scar tissue compared to contusion injuries.
Each model has strengths depending on study objectives, and our team can help determine the best choice for your research. Reach out to discuss which model is most appropriate for your SCI study.
What is the dropout rate and how do you take this into account?
The dropout rate in SCI studies is approximately 20%. This means that out of every 12 animals in a group, around 3 may be lost due to complications. Planning studies with this rate in mind ensures robust statistical power for your studies. Contact our scientific team to determine the optimal number of animals for your experiments to reach statistical significance.
How do you exclude animals? What is considered an outlier?
Exclusion of animals can be based on several specific criteria, including:
- Surgical anomalies: Sham animals showing bruising of the spinal cord as a result of the (sham) hemisection surgery may no longer qualify as true controls.
- Functional recovery data: Animals are excluded if recovery outcomes indicate the injury was either too severe or too mild.
These criteria ensure that consistent and reliable data are included in analyses. Reach out to learn more about how we ensure reliability and consistency in your SCI study.
Can InnoSer also work with other spinal cord injury mouse models?
Yes, InnoSer offers expertise in multiple spinal cord injury models, including contusion SCI models and laceration SCI mouse models. Additionally, InnoSer’s Spa mouse model of spasticity may represent another translationally relevant model. Each model has unique features. Collaborating closely with our experts ensures the design of a study tailored to your therapeutic compound and research goals. Contact us to discuss your compound’s mechanism of action (MoA) and the most suitable SCI mouse model for testing.
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