The Role of Functional Neuroanatomy of the Lumbar Spinal Cord in Effect of Epidural Stimulation

Cuellar, Carlos A.; Mendez, Aldo A; Islam, Riazul; Calvert, Jonathan S.; Grahn, Peter J.; Knudsen, Bruce E.; Pham, Tuan D.; Lee, Kendall H.; Lavrov, Igor

doi:10.3389/fnana.2017.00082

Cited by 42 publications

(58 citation statements)

References 57 publications

(100 reference statements)

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“…In turn, the physiological spread of the stimulation-induced excitatory drive due to fibers' collaterals defines the upper-bounds of the potential for spatial specificity. Therefore, the optimization of spinal implants requires integrating not only the dimensions of spinal segments but also the path of the dorsal roots in the design of electrode locations 8,20,39 (Fig. 2).…”

Section: Anatomical Considerationsmentioning

confidence: 99%

Configuration of electrical spinal cord stimulation through real-time processing of gait kinematics

et al. 2018

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Epidural electrical stimulation (EES) of the spinal cord and real-time processing of gait kinematics are powerful methods for the study of locomotion and the improvement of motor control after injury or in neurological disorders. Here, we describe equipment and surgical procedures that can be used to acquire chronic electromyographic (EMG) recordings from leg muscles and to implant targeted spinal cord stimulation systems that remain stable up to several months after implantation in rats and nonhuman primates. We also detail how to exploit these implants to configure electrical spinal cord stimulation policies that allow control over the degree of extension and flexion of each leg during locomotion. This protocol uses real-time processing of gait kinematics and locomotor performance, and can be configured within a few days. Once configured, stimulation bursts are delivered over specific spinal cord locations with precise timing that reproduces the natural spatiotemporal activation of motoneurons during locomotion. These protocols can also be easily adapted for the safe implantation of systems in the vicinity of the spinal cord and to conduct experiments involving real-time movement feedback and closed-loop controllers.

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Section: Anatomical Considerationsmentioning

confidence: 99%

Configuration of electrical spinal cord stimulation through real-time processing of gait kinematics

et al. 2018

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“…Electrophysiological tests were performed under anesthesia on experimental pigs before the injury, at 15 min, and at 6 and 22 weeks after SCI. The M-and H-waves (pigs only have M-response) from the tibialis anterior muscle in pigs and the gastrocnemius muscle in rats were recorded in response to stimulation of the sciatic nerve [37,38].…”

Section: Electrophysiological Studiesmentioning

confidence: 99%

Mesenchymal Stem Cell Therapy for Spinal Cord Contusion: A Comparative Study on Small and Large Animal Models

et al. 2019

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Here, we provide a first comparative study of the therapeutic potential of allogeneic mesenchymal stem cells derived from bone marrow (BM-MSCs), adipose tissue (AD-MSCs), and dental pulp (DP-MSCs) embedded in fibrin matrix, in small (rat) and large (pig) spinal cord injury (SCI) models during subacute period of spinal contusion. Results of behavioral, electrophysiological, and histological assessment as well as immunohistochemistry and real-time polymerase chain reaction analysis suggest that application of AD-MSCs combined with a fibrin matrix within the subacute period in rats (2 weeks after injury), provides significantly higher post-traumatic regeneration compared to a similar application of BM-MSCs or DP-MSCs. Within the rat model, use of AD-MSCs resulted in a marked change in: (1) restoration of locomotor activity and conduction along spinal axons; (2) reduction of post-traumatic cavitation and enhancing tissue retention; and (3) modulation of microglial and astroglial activation. The effect of an autologous application of AD-MSCs during the subacute period after spinal contusion was also confirmed in pigs (6 weeks after injury). Effects included: (1) partial restoration of the somatosensory spinal pathways; (2) reduction of post-traumatic cavitation and enhancing tissue retention; and (3) modulation of astroglial activation in dorsal root entry zone. However, pigs only partially replicated the findings observed in rats. Together, these results indicate application of AD-MSCs embedded in fibrin matrix at the site of SCI during the subacute period can facilitate regeneration of nervous tissue in rats and pigs. These results, for the first time, provide robust support for the use of AD-MSC to treat subacute SCI.

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“…Multiple computational (9-11) and animal studies (13,25) demonstrated that dorsal roots and dorsal columns are the main target for EES, which emphasizes the importance of electrodes location in relation to the main target structures (9)(10)(11)(12). It has been reported that electrical stimulation applied at DREZ provides significantly higher motor evoked responses compared to other electrodes location on dura mater (3,13). Orientation of electrical field along the fibers of target structures is another key factor in effect of EES (8).…”

Section: Discussionmentioning

confidence: 99%

Segment-specific orientation of the dorsal and ventral roots for precise therapeutic targeting of human spinal cord

Mendez

Islam

Latypov

et al. 2020

Preprint

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One Sentence Summary: This is the first detailed analysis of the segment-specific dorsal and ventral spinal roots spatial orientation measured and correlated to the anatomical landmarks of the spinal cord and vertebral column for human.Abstract: An understanding of spinal cord functional neuroanatomy is essential for diagnosis and treatment of multiple disorders including, chronic pain, movement disorders, and spinal cord injury. Till now, no information is available on segment-specific spinal roots orientation in humans. In this study we collected neuroanatomical measurements of the dorsal and ventral roots from C2-L5, as well as spinal cord and vertebral bone measurements from adult cadavers. Spatial orientation of dorsal and ventral roots were measured and correlated to the anatomical landmarks of the spinal cord and vertebral column. The results show less variability in rostral root angles compared to the caudal angles across all segments. Dorsal and ventral rootlets were oriented mostly perpendicular to the spinal cord at the cervical level and demonstrate more parallel orientation at the thoracic and lumbar segments. The number of rootlets was the highest in dorsal cervical and lumbar segments. Spinal cord transverse diameter and size of the dorsal columns were largest at cervical and lumbar segments. The strongest correlation was found between the length of intervertebral foramen to rostral rootlet and vertebral bone length. These results could be used to locate spinal roots and spinal cord landmarks based on bone marks on CT or X-rays. These results also provide background for future correlations between anatomy of spinal cord and spinal column structures that could improve stereotactic surgical procedures and electrode positioning for spinal cord neuromodulation.Intervertebral foramen to rostral rootlet distance: Similar to previous measurement, intervertebral foramen to rostral rootlet distance was gradually increased to the greatest values at lumbar segments (9.59 ± 2.55 cm) (p<0.001) (Fig. 1G). This distance at C2 segment was 1.55 ± 0.42 cm and it did not change significantly throughout cervical segments till C7, where C7 (2.01 ± 0.08 cm) and C8 (2.27 ± 0.22 cm) were significantly greater compare to C5. Lower cervical and upper thoracic segments did not vary significantly till T3, where there it increased (4.05 ± 0.63 cm). No other major variations were observed across the rest of thoracic segments except for T12 (5.68 ± 0.92 cm) that was significantly longer compare to T1-T10. T12, L1, and L2 segments did not vary, but L3 (10.27 ± 2.23 cm) showed significant increase compared to L1. No major variations were observed for the rest of lumbar segments, although at L5 (12.66 ± 1.50 cm) it was significantly longer than at L2 (Fig. 1I, purple line).

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The Role of Functional Neuroanatomy of the Lumbar Spinal Cord in Effect of Epidural Stimulation

Cited by 42 publications

References 57 publications

Configuration of electrical spinal cord stimulation through real-time processing of gait kinematics

Configuration of electrical spinal cord stimulation through real-time processing of gait kinematics

Mesenchymal Stem Cell Therapy for Spinal Cord Contusion: A Comparative Study on Small and Large Animal Models

Segment-specific orientation of the dorsal and ventral roots for precise therapeutic targeting of human spinal cord

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