Refining Stereotaxic Neurosurgery Techniques and Welfare Assessment for Long-Term Intracerebroventricular Device Implantation in Rodents
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Implantable Devices
2.3. Intrathecal Implantable Device Surgery
2.3.1. Preoperative Care and Treatment
2.3.2. Stereotaxic Surgery Procedure
2.3.3. Postoperative Care
2.4. Body Weight Monitoring and Welfare Assessment
2.5. Behavioral Analysis
2.6. Catheter Placement Validation
2.6.1. In Vivo Dye Infusion and Visualization
2.6.2. Histological Analysis
2.7. Statistics
3. Results
3.1. The Optimized Protocol of Stereotaxic Surgeries Shortens the Recovery Time Required after Surgery and Significantly Minimizes Humane Endpoint Application
3.2. Improved Protocol Reduces the Drop in Body Weight Observed in Mice from the First Postoperative Surgery Onwards and Normalizes It over Time
3.3. Optimized Protocol and Implantation of Smaller Devices Significantly Improve Animal Welfare and Enable Longer and Safer Experimental Periods
3.4. Optimized Intrathecal Implantation Procedures Do Not Appear to Negatively Affect General and Anxiety-like Behaviors for at Least Two Months after Surgery
3.5. Validation of Cannula Placement Is Required after Experiment Termination to Confirm Correct Implantation at the Stereotaxic Coordinates of Interest
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Parameter and Time Analyzed | Naïve | Original Device | Miniaturized Device | Alzet Pump a | ||||
---|---|---|---|---|---|---|---|---|
WT | APP | WT | APP | WT | APP | WT | APP | |
Recovery time after surgery | 10 | 10 | 9 | 10 | 3 | 10 | 10 | 10 |
Humane endpoint application | 10 | 10 | 9 | 10 | 3 | 10 | 10 | 10 |
Body weight at W1 | 10 | 10 | 9 | 10 | 3 | 10 | 10 | 10 |
Body weight at W3 | 10 | 10 | 7 | 7 | 3 | 9 | 10 | 9 |
Body weight at W8 | 5 | 5 | - | - | 3 | 9 | - | - |
% Change in body weight at W0 | 10 | 10 | 9 | 10 | 3 | 10 | 10 | 10 |
% Change in body weight at W3 | 10 | 10 | 7 | 7 | 3 | 9 | 10 | 9 |
% Change in body weight at W8 | 5 | 5 | - | - | 3 | 9 | - | - |
Welfare assessment score at W3 | 10 | 10 | 7 | 7 | 3 | 9 | 10 | 9 |
Welfare assessment score at W8 | 5 | 5 | - | - | 3 | 9 | - | - |
Behavioral testing at W1 | 10 | 10 | - | - | 3 | 9 | 9 | 10 |
Behavioral testing at W4/5 | 10 | 10 | - | - | 3 | 9 | 9 | 9 |
Behavioral testing at W8 | 6 | 5 | - | - | 3 | 9 | - | - |
Parameter | Original Device | Miniaturized Device | ALZET® Pump 1004 a |
---|---|---|---|
Weight (filled; g) | 4.29 ± 0.41 | 2.25 ± 0.15 | 0.56 ± 0.06 |
% Weight (with respect to animal body weight b; %) | 14.16 ± 1.35 | 6.93 ± 0.46 | 1.85 ± 0.19 |
Total Volume (cm3) | 5.92 | 2.54 | 0.54 |
Maximum L (cm) | 3.5 | 2.9 | 1.5 |
Maximum W (cm) | 1.5 | 1.3 | 0.6 |
Maximum H (cm) | 1.5 | 0.9 | 0.6 |
Coated Material | Polyetheretherketone (PEEK; ISO 13485 [29]) | LOCTITE® SI 5248 silicone (Henkel, Düsseldorf, Germany; ISO 10993 [30]) | Cellulose ester blend |
Catheter Tube Length and Outside Diameter (cm) | 3 ± 0.2, 0.11 ± 0.008 | 3 ± 0.2, 0.11 ± 0.008 | 3 ± 0.2, 0.11 ± 0.008 |
Catheter Tube Material and Configuration | Polyvinyl chloride (MG), pre-attached | Polyvinyl chloride (MG), pre-attached | Polyvinyl chloride (MG), attachable |
Brain Infusion III Cap Cannula Dimensions (L, W, H; cm) c | 0.59, 0.59, 0.2 | 0.59, 0.59, 0.2 | 0.59, 0.59, 0.2 |
Brain Infusion III Cap Material c | Polycarbonate | Polycarbonate | Polycarbonate |
Brain Infusion III Cannula Dimensions (L, W, H; cm) c | 0.3, 0.031, 0.031 | 0.3, 0.031, 0.031 | 0.3, 0.031, 0.031 |
Brain Infusion III Cannula Material c | Stainless steel | Stainless steel | Stainless steel |
Parameter | Original Device | Miniaturized Device | ALZET® Pump 1004 a |
---|---|---|---|
Apheresis Module Dimensions (L, W, H; cm) | 1.4, 1.5, 1.5 | 1.3, 1.3, 0.9 | - |
Apheresis Module External Volume (cm3) | 3.150 | 1.521 | - |
Apheresis Module Internal Volume (µL) | 235.5 | 235.5 | - |
Reservoir Dimensions (L, W, H; cm) | 2.1, 1.2, 1.1 | 1.6, 0.8, 0.8 | 1.5, 0.6, 0.6 |
Reservoir External Volume (cm3) | 2.772 | 1.024 | 0.540 |
Reservoir Internal Volume (µL) | 100 | 100 | 100 |
Total Volume (cm3) | 5.922 | 2.545 | 0.540 |
Parameters | Score | |
---|---|---|
General Condition, Physical Appearance, and Posture | ||
Smooth and shiny fur, clean forelimbs, and nose | 0 | |
Presence of piloerection, unkempt fur | 1 | |
Abnormal posture (abdominal curvature and/or kyphosis, increased muscle tone) | 2 | |
Skin lesions unrelated to surgery (ear dermatitis, scratches, excessive barbering) | 2 | |
Nutritional and Hydration Status | ||
Unaffected or increased | 0 | |
Dehydration signs | <2 s after pinching the back skin | 1 |
>2 s after pinching the back skin | 2 | |
Animal Body weight | 1 ≤ 10% weight loss | 1 |
10–20% weight loss | 4 | |
>20% weight loss (duration >4 postoperative days) | 8 | |
Spontaneous Behavior | ||
Normal behavior (sleeping, exploration, grooming, nesting, interaction with environmental enrichment objects) | 0 | |
No use of enrichment objects, no nesting behavior | 1 | |
Impairment of motor function (hypo-locomotion) | 4 | |
Lethargy and/or slight loss of balance | 8 | |
Hind-limbs paralysis, tremors and/or signs of vestibulocochlear dysfunction | 12 | |
Surgery-specific Parameters | ||
Clean and dry surgical incision, no signs of infection, no pain or signs of distress | 0 | |
Scratches around the scar or slight redness | 1 | |
Redness and/or necrosis of the skin around the scar | 3 | |
Grimace scale | Moderate | 4 |
Severe | 6 | |
Suture opening Grade I (loose stitches with closed and healed wound) | 3 | |
Suture opening Grade II (loose stitches with unhealed wound) | 6 | |
Suture opening Grade III (open unhealed wound) | 10 | |
Suture opening Grade IV (Brain Infusion Kit cannula disconnected) | 12 |
Parameter | Comparisons and p-Values | |||
---|---|---|---|---|
Recovery time | Original Device | Miniaturized Device | Alzet Pump | |
>20 min | <0.001 | 0.002 | <0.001 | |
5–10 min | 0.284 | 0.003 | 0.151 | |
<5 min | <0.001 | 0.341 | <0.001 | |
Naïve | Original Device | Miniaturized Device | Alzet Pump | |
Humane endpoint | 0.029 | <0.001 | 0.681 | 0.159 |
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Pérez-Martín, E.; Coto-Vilcapoma, A.; Castilla-Silgado, J.; Rodríguez-Cañón, M.; Prado, C.; Álvarez, G.; Álvarez-Vega, M.A.; Fernández-García, B.; Menéndez-González, M.; Tomás-Zapico, C. Refining Stereotaxic Neurosurgery Techniques and Welfare Assessment for Long-Term Intracerebroventricular Device Implantation in Rodents. Animals 2023, 13, 2627. https://doi.org/10.3390/ani13162627
Pérez-Martín E, Coto-Vilcapoma A, Castilla-Silgado J, Rodríguez-Cañón M, Prado C, Álvarez G, Álvarez-Vega MA, Fernández-García B, Menéndez-González M, Tomás-Zapico C. Refining Stereotaxic Neurosurgery Techniques and Welfare Assessment for Long-Term Intracerebroventricular Device Implantation in Rodents. Animals. 2023; 13(16):2627. https://doi.org/10.3390/ani13162627
Chicago/Turabian StylePérez-Martín, Ester, Almudena Coto-Vilcapoma, Juan Castilla-Silgado, María Rodríguez-Cañón, Catuxa Prado, Gabriel Álvarez, Marco Antonio Álvarez-Vega, Benjamín Fernández-García, Manuel Menéndez-González, and Cristina Tomás-Zapico. 2023. "Refining Stereotaxic Neurosurgery Techniques and Welfare Assessment for Long-Term Intracerebroventricular Device Implantation in Rodents" Animals 13, no. 16: 2627. https://doi.org/10.3390/ani13162627