Activation of the sciatic nerve evoked during epidural spinal cord stimulation in rodents

2019 ◽  
Vol 2 (2) ◽  
pp. 63-71
Author(s):  
Narendra Bhadra ◽  
Tina Vrabec ◽  
Kevin Kilgore ◽  
Niloy Bhadra

Aim: To validate the use of motor activation thresholds (MoT) to titrate stimulation amplitudes for spinal cord stimulation in rodent models. Methods: We recorded thresholds for MoT and sciatic compound action potentials in ten Sprague-Dawley rats implanted with epidural electrodes. Strength duration curves were fitted to the threshold values. Results: Activation thresholds were in the same order for both MoT and sciatic compound action potentials. Conclusion: Many of the large, myelinated fibers traversing the dorsal columns in the rodent spine are activated at similar current levels to MoT. Epidural stimulation in rodents needs to be applied at amplitudes close to MoT to activate these axons.

2019 ◽  
Vol 23 (1) ◽  
pp. 82-95 ◽  
Author(s):  
John L. Parker ◽  
Milan Obradovic ◽  
Nastaran Hesam Shariati ◽  
Robert B. Gorman ◽  
Dean M. Karantonis ◽  
...  

2011 ◽  
Vol 105 (2) ◽  
pp. 929-941 ◽  
Author(s):  
Alexander A. Velumian ◽  
Yudi Wan ◽  
Marina Samoilova ◽  
Michael G. Fehlings

Unlike recordings derived from optic nerve or corpus callosum, compound action potentials (CAPs) recorded from rodent spinal cord white matter (WM) have a characteristic single-peak shape despite the heterogeneity of axonal populations. Using a double sucrose gap technique, we analyzed the CAPs recorded from dorsal, lateral, and ventral WM from mature rat spinal cord. The CAP decay was significantly prolonged with increasing stimulus intensities suggesting a recruitment of higher threshold, slower conducting axons. At 3.5 mm conduction distance, a hidden higher threshold, slower conducting component responsible for prolongation of CAP decay was uncovered in 22 of 25 of dorsal WM strips by analyzing the stimulus-response relationships and a normalization-subtraction procedure. This component had a peak conduction velocity (CV) of 5.0 ± 0.2 (SE) m/s as compared with 9.3 ± 0.5 m/s for the lower threshold peak ( P < 0.0001). Oxygen-glucose deprivation (OGD), along with its known effects on CAP amplitude, significantly ( P < 0.015) shortened the CAP decay. The hidden higher threshold, slower conducting component showed greater sensitivity to OGD compared with the lower threshold, faster conducting component, suggesting a differential sensitivity of axonal populations of spinal cord WM. At longer conduction distances and lower temperatures (9.8 mm, 22–24°C), the slower peak could be directly visualized in CAPs at higher stimulation intensities. A detailed analysis of single-peak CAPs to identify their fast and slow conducting components may be of particular importance for studies of axonal physiology and pathophysiology in small animals where the conduction distance is not sufficiently long to separate the CAP peaks.


2013 ◽  
Vol 16 (4) ◽  
pp. 295-303 ◽  
Author(s):  
John L. Parker ◽  
Dean M. Karantonis ◽  
Peter S. Single ◽  
Milan Obradovic ◽  
James Laird ◽  
...  

1990 ◽  
Vol 152 (1) ◽  
pp. 1-15
Author(s):  
J. G. Nicholls ◽  
R. R. Stewart ◽  
S. D. Erulkar ◽  
N. R. Saunders

1. The entire central nervous system (CNS) was isolated from 1- to 4-day-old newborn South American opossums (Monodelphis domestica). At this stage the CNS has only an embryonic forebrain (two-layered) and no cerebellum and corresponds to a 14-day rat embryo. Its eyes, ears and hind-limbs are only at an early stage of formation. The isolated CNS preparations continue to develop and to produce electrical signals for up to 4 days in oxygenated Krebs' fluid at 23 degrees C. 2. The longitudinal axis of the CNS showed markedly different stages of development. More neuroblast cells were present in the proliferative zone in lumbosacral than in cervical or thoracic regions of the cord. 3. The progeny of dividing cells were labelled in isolated preparations by applying bromodeoxyuridine (BrdU) to the bathing solution for 2 h. Stained precursor cells were observed in CNS that had been left in Krebs' fluid for 4 days before applying BrdU and also in CNS that had been exposed to BrdU shortly after dissection and then left for 4 days. 4. Compound action potentials were evoked from the isolated CNS by stimulation with extracellular electrodes. Compound action potentials increased in amplitude with stronger stimulation and showed discrete peaks of conduction velocity. All electrical activity was eliminated reversibly by 0.1 mumol l-1 tetrodotoxin applied to the bathing solution. Block and recovery occurred with a half-time of approximately 5 min. High concentrations of magnesium (20 mmol l-1) reversibly blocked slower components of the volley. 5. Reflexes in cervical and thoracic segments of the spinal cord continued to function in isolated preparations. Stimulation of a dorsal root evoked bursts of impulses in the appropriate ventral root. Spontaneous and evoked activity in ventral roots was eliminated reversibly by 20 mmol l-1 magnesium. 6. In thoracic segments, spontaneous rhythmical bursts of action potentials were recorded. Burst activity was correlated with respiratory movements of the ribs in semi-intact preparations in which a few ribs and muscles were left attached to the isolated CNS. 7. At raised temperatures of 28 degrees C compared to 23 degrees C both spontaneous and evoked electrical activity were reversibly reduced. 8. Together these results show that the isolated CNS of the newborn opossum survives well in culture. The preparation offers advantages for pharmacological and physiological studies of spinal reflexes, for analysis of the mechanisms underlying rhythmical respiratory activity and for following the time course of CNS development in vitro.


Pain ◽  
2012 ◽  
Vol 153 (3) ◽  
pp. 593-601 ◽  
Author(s):  
John L. Parker ◽  
Dean M. Karantonis ◽  
Peter S. Single ◽  
Milan Obradovic ◽  
Michael J. Cousins

2000 ◽  
Vol 5 (4) ◽  
pp. 227-235 ◽  
Author(s):  
Sidney Ochs ◽  
Rahman Pourmand ◽  
Kenan Si ◽  
Richard N. Friedman

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Paige Smith ◽  
Natalia Ogrodnik ◽  
Janani Satkunarajah ◽  
Meaghan A. O’Reilly

AbstractExtensive studies on focused ultrasound (FUS)-mediated drug delivery through the blood–brain barrier have been published, yet little work has been published on FUS-mediated drug delivery through the blood-spinal cord barrier (BSCB). This work aims to quantify the delivery of the monoclonal antibody trastuzumab to rat spinal cord tissue and characterize its distribution within a model of leptomeningeal metastases. 10 healthy Sprague–Dawley rats were treated with FUS + trastuzumab and sacrificed at 2-h or 24-h post-FUS. A human IgG ELISA (Abcam) was used to measure trastuzumab concentration and a 12 ± fivefold increase was seen in treated tissue over control tissue at 2 h versus no increase at 24 h. Three athymic nude rats were inoculated with MDA-MB-231-H2N HER2 + breast cancer cells between the meninges in the thoracic region of the spinal cord and treated with FUS + trastuzumab. Immunohistochemistry was performed to visualize trastuzumab delivery, and semi-quantitative analysis revealed similar or more intense staining in tumor tissue compared to healthy tissue suggesting a comparable or greater concentration of trastuzumab was achieved. FUS can increase the permeability of the BSCB, improving drug delivery to specifically targeted regions of healthy and pathologic tissue in the spinal cord. The achieved concentrations within the healthy tissue are comparable to those reported in the brain.


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