Evaluation of neurotoxicity and long-term function and behavior following intrathecal 1 % 2-chloroprocaine in juvenile rats
| Autor: | Marjorie R. Grafe, Suellen M. Walker, Shelle Malkmus, Veronica I. Shubayev, Amanda J. Roberts, Tony L. Yaksh, Susan B. Powell, Kelly A. Eddinger, Joanne Steinauer |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Cauda Equina medicine.drug_class medicine.medical_treatment Morris water navigation task Motor Activity Toxicology Open field Rats Sprague-Dawley Lumbar Morris Water Maze Test Medicine Animals Saline Injections Spinal business.industry Local anesthetic Caspase 3 General Neuroscience Cauda equina Sensory Gating Spinal cord Rats Lumbar Spinal Cord medicine.anatomical_structure Anesthesia Female Neurotoxicity Syndromes business Procaine |
| Zdroj: | Neurotoxicology. 88 |
| ISSN: | 1872-9711 |
| Popis: | Spinally-administered local anesthetics provide effective perioperative anesthesia and/or analgesia for children of all ages. New preparations and drugs require preclinical safety testing in developmental models. We evaluated age-dependent efficacy and safety following 1% preservative-free 2-chloroprocaine (2-CP) in juvenile Sprague-Dawley rats. Percutaneous lumbar intrathecal 2-CP was administered at postnatal day (P)7, 14 or 21. Mechanical withdrawal threshold pre- and post-injection evaluated the degree and duration of sensory block, compared to intrathecal saline and naive controls. Tissue analyses one- or seven-days following injection included histopathology of spinal cord, cauda equina and brain sections, and quantification of neuronal apoptosis and glial reactivity in lumbar spinal cord. Following intrathecal 2-CP or saline at P7, outcomes assessed between P30 and P72 included: spinal reflex sensitivity (hindlimb thermal latency, mechanical threshold); social approach (novel rat versus object); locomotor activity and anxiety (open field with brightly-lit center); exploratory behavior (rearings, holepoking); sensorimotor gating (acoustic startle, prepulse inhibition); and learning (Morris Water Maze). Maximum tolerated doses of intrathecal 2-CP varied with age (1.0 μL/g at P7, 0.75 μL/g at P14, 0.5 μL/g at P21) and produced motor and sensory block for 10-15 minutes. Tissue analyses found no significant differences across intrathecal 2-CP, saline or naive groups. Adult behavioral measures showed expected sex-dependent differences, that did not differ between 2-CP and saline groups. Single maximum tolerated in vivo doses of intrathecal 2-CP produced reversible spinal anesthesia in juvenile rodents without detectable evidence of developmental neurotoxicity. Current results cannot be extrapolated to repeated dosing or prolonged infusion. |
| Databáze: | OpenAIRE |
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