Comparative evaluation of contusion spinal cord injury models from ventral and dorsal approaches in rabbits in an experiment

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Abstract

BACKGROUND: Contemporary experimental models for spinal cord injury studies are mainly based on spinal cord injury in rats and mice. Modeling of experimental spinal cord injuries is generally performed from the dorsal approach, which excludes its injury as a result of compression by the fragments of the fractured vertebral body and significantly restricts the application of the results obtained from clinical practice.

AIM: To develop and create contusional spinal cord injury model from the ventral approach with its subsequent comparison with the contusional spinal cord injury model from the dorsal approach.

MATERIALS AND METHODS: The study examined 20 female Soviet Chinchilla rabbits weighing 3.5–4.5 kg. The rabbits were subjected to standardized spinal cord injuries from the ventral and dorsal approaches at the LII level. Somatosensory- and motor-evoked potentials, H-reflex, were recorded in all experimental animals before injury, immediately after, and 3 and 8 h after injury. Histological studies were also performed using qualitative and semiquantitative analyses of biopsy samples of damaged areas and assessing the number of dystrophic neurons over time. The results of neurophysiological and histological examinations of the spinal cord in cases of ventral and dorsal trauma were statistically processed.

RESULTS: When modeling spinal cord injury from the ventral approach, in comparison with the model from the dorsal approach, more significant damage is detected. As a result of the injury factor, the dysfunction of both neurons at the traumatization level and peripheral neurons below the injury zone was revealed; however, as histological examinations have shown, in contrast to the dorsal approach, mild hemorrhage was observed in the ventral approach.

CONCLUSIONS: The results obtained indicate a more significant and strict contusion mechanism of the spinal cord injury model from the ventral approach and the maximum proximity of the resulting model in a clinical situation. In the future, the experimental model of the contusional spinal cord injury in a laboratory animal can be used in chronic experiments.

About the authors

Anton S. Shabunin

H. Turner National Medical Research Center for Сhildren’s Orthopedics and Trauma Surgery; Peter the Great Saint Petersburg Polytechnic University

Author for correspondence.
Email: anton-shab@yandex.ru
ORCID iD: 0000-0002-8883-0580
SPIN-code: 1260-5644

MD, Research Associate

Russian Federation, Saint Petersburg; Saint Petersburg

Margarita V. Savina

H. Turner National Medical Research Center for Сhildren’s Orthopedics and Trauma Surgery

Email: drevma@yandex.ru
ORCID iD: 0000-0001-8225-3885
SPIN-code: 5710-4790

MD, PhD, Cand. Sci. (Med.)

Russian Federation, Saint Petersburg

Timofey S. Rybinskikh

H. Turner National Medical Research Center for Children’s Orthopedics and Trauma Surgery

Email: timofey1999r@gmail.com
ORCID iD: 0000-0002-4180-5353
SPIN-code: 7739-4321

resident

Russian Federation, Saint Petersburg

Anna D. Dreval

H. Turner National Medical Research Center for Сhildren’s Orthopedics and Trauma Surgery

Email: anndreval@yandex.ru
ORCID iD: 0009-0007-3985-634X
SPIN-code: 4175-6620

student

Russian Federation, Saint Petersburg

Vladislav D. Safarov

H. Turner National Medical Research Center for Сhildren’s Orthopedics and Trauma Surgery; Peter the Great Saint Petersburg Polytechnic University

Email: vladsafarov.vs@mail.ru
ORCID iD: 0009-0006-2948-133X
SPIN-code: 5240-1801

student

Russian Federation, Saint Petersburg; Saint Petersburg

Platon А. Safonov

H. Turner National Medical Research Center for Сhildren’s Orthopedics and Trauma Surgery

Email: safo165@gmail.com
ORCID iD: 0009-0006-7554-1292
SPIN-code: 6088-1297

student

Russian Federation, Saint Petersburg

Andrey M. Fedyuk

H. Turner National Medical Research Center for Сhildren’s Orthopedics and Trauma Surgery

Email: Andrej.fedyuk@gmail.com
ORCID iD: 0000-0002-2378-2813
SPIN-code: 3477-0908

resident

Russian Federation, Saint Petersburg

Daria A. Sitovskaia

Polenov Neurosurgical Institute

Email: daliya_16@mail.ru
ORCID iD: 0000-0001-9721-3827
SPIN-code: 3090-4740

MD, pathologist, researcher

Russian Federation, Saint Petersburg

Nikita M. Dyachuk

H. Turner National Medical Research Center for Сhildren’s Orthopedics and Trauma Surgery

Email: wrwtit@yandex.ru
ORCID iD: 0009-0009-4384-9526

student

Russian Federation, Saint Petersburg

Alexandra S. Baidikova

H. Turner National Medical Research Center for Сhildren’s Orthopedics and Trauma Surgery

Email: baidikovaalexandra@yandex.ru
ORCID iD: 0009-0008-8785-0193
SPIN-code: 7805-1341

student

Russian Federation, Saint Petersburg

Lidia S. Konkova

H. Turner National Medical Research Center for Сhildren’s Orthopedics and Trauma Surgery

Email: lidia.kireeva@yandex.ru
ORCID iD: 0009-0007-5400-3513
SPIN-code: 3527-7121

MD, PhD student

Russian Federation, Saint Petersburg

Olga L. Vlasova

Peter the Great Saint Petersburg Polytechnic University

Email: vlasova.ol@spbstu.ru
ORCID iD: 0000-0002-9590-703X
SPIN-code: 7823-8519

PhD, Dr. Sc. (Phys. and Math.), Assistant Professor

Russian Federation, Saint Petersburg

Sergei V. Vissarionov

H. Turner National Medical Research Center for Сhildren’s Orthopedics and Trauma Surgery

Email: vissarionovs@gmail.com
ORCID iD: 0000-0003-4235-5048
SPIN-code: 7125-4930

MD, PhD, Dr. Sci. (Med.), Professor, Corresponding Member of RAS

Russian Federation, Saint Petersburg

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2. Fig. 3. Photographs of the impact rig in the assembly

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3. Fig. 1. Scheme of the registration of neurophysiological parameters of the experimental animal: a, somatosensory-evoked potentials (1, a stimulating electrode on the sciatic nerve; 2.1, a registering electrode on the cerebral cortex; 2.2, a registering electrode on the lumbar thickness of the spinal cord); b, motor-evoked potentials (1, a stimulating electrode in the projection of the motor zone of the cerebral cortex; 2.1, a recording electrode on the triceps brachii; 2.2, a recording electrode on the calf muscle); c, H-reflex (1, a stimulating electrode on the sciatic nerve; 2, a recording electrode on the calf muscle)

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4. Fig. 2. Scheme of the implantation of intracranial electrodes: a, scheme of marking the installation zones of the intracranial electrodes (actively, frontally and referentially, and dorsally), stimulating motor-evoked potentials, and registering somatosensory-evoked potentials; b, surgical field with holes prepared for implantation.

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5. Fig. 4. Motor-evoked potentials from the hind limb (1 and 2 ch.) and forelimb (3 ch.) in a normal rabbit before injury modeling (4 ms/2 mV scale). ch, channel (leads)

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6. Fig. 5. Motor-evoked potentials 8 h after spinal cord injury modeling from the dorsal and ventral approaches (4 ms/2 mV scale). Motor-evoked potentials from the hind limbs are absent

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7. Fig. 6. H-reflex in a rabbit with the dorsal approach before (a) and 8 h after (b) dorsal injury (5 ms/15 mV/1 mV scale): a, H-reflex and M-response are registered before injury; b, polysynaptic responses are registered in large numbers 8 h after injury

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8. Fig. 7. Somatosensory-evoked potentials in normal rabbits; 1 ch., evoked potential from the projection zones of the cerebral cortex; 2 ch., evoked potential from the level of lumbar thickening (10 ms/15 μV scale). ch, channel (leads)

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9. Fig. 8. Somatosensory-evoked potentials in a rabbit before (a) and after (b) injury: the first channel showed cortical responses, whereas the second channel presented responses from the lumbar level (10 ms/15 μV scale): a, spinal and cortical potentials are registered before injury; b, a potential from the lumbar level is registered after injury, and there is no cortical response, indicating a complete disruption of conduction along the somatosensory pathways of the spinal cord at the injury level. The amplitudes of the lumbar response are increased. ch, channel (leads)

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10. Fig. 9. Comparison of somatosensory-evoked potential curves during withdrawal from lumbar thickening after spinal cord injury modeling using ventral and dorsal approaches: a, immediately after injury; b, at 3 h; c, at 8 h. At 8 h after injury, the amplitude of somatosensory-evoked potentials during withdrawal from the lumbar thickening increased. DI, dorsal injury; VI, ventral injury

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11. Fig. 10. Hemorrhages in the spinal cord injury area, hematoxylin and eosin staining: a, dorsal injury, massive hemorrhage in the area of anterior and lateral tubules (transverse section, ×50); b, dorsal injury, massive hemorrhage in the area of anterior and lateral tubules (longitudinal section, ×50); c, ventral trauma, small focal hemorrhages in the gray matter of the spinal cord (transverse section, ×50); d, ectasized vessel with thrombotic masses in the lumen (longitudinal section, ×100)

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12. Fig. 11. Neuronal changes in the spinal cord injury area, hematoxylin and eosin staining: a, dystrophic changes in neurons (longitudinal section, ×100); the black arrows indicate hydropic swelling and tigrolysis, and empty arrows indicate dark-type dystrophy; b, hydropic swelling and tigrolysis of Nissl substance (transverse section, ×400); c, dark-type dystrophy of neurons; the arrows indicate large vacuoles in the cytoplasm (transverse section, ×400)

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13. Fig. 12. Dystrophic changes in the neurons of the anterior horn of the spinal cord at injury by the dorsal approach, staining with hematoxylin and eosin: a and b, 99% of the altered neurons in the area of the anterior horn of the spinal cord (cross section, ×100)

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14. Fig. 13. Diffuse axonal damage in traumatic spinal cord injury. Longitudinal sections, hematoxylin and eosin staining: a, numerous thickened and deformed axons (arrows), ×100; b, progression of the diffuse axonal damage with the formation of club-like thickening and axonal ruptures, ×400; c, axonal rupture with the formation of eosinophilic axonal spheres, ×400; d, amyloid calf (arrow) at the border of gray and white matter, diffuse edema and neuropil unfolding, ×400

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