Manganese-enhanced MRI Offers Correlation with Severity of Spinal Cord Injury in Experimental Models

Background: Spinal cord injuries (SCI) are clinically challenging, because neural regeneration after cord damage is unknown. In SCI animal models, regeneration is evaluated histologically, requiring animal sacrifice. Noninvasive techniques are needed to detect longitudinal SCI changes. Objective: To compare manganese-enhanced magnetic resonance imaging (MRI [MEMRI]) in hemisection and transection of SCI rat models with diffusion tensor imaging (DTI) and histology. Methods: Rats underwent T9 spinal cord transection (n=6), hemisection (n=6), or laminectomy without SCI (controls, n=6). One-half of each group received lateral ventricle MnCl2 injections 24 hours later. Conventional DTI or T1-weighted MRI was performed 84 hours post-surgery. MEMRI signal intensity ratio above and below the SCI level was calculated. Fractional anisotropy (FA) measurements were taken 1 cm rostral to the SCI. The percentage of FA change was calculated 10 mm rostral to the SCI epicenter, between FA at the dorsal column lesion normalized to a lateral area without FA change. Myelin load (percentage difference) among groups was analyzed by histology. Results: In transection and hemisection groups, mean MEMRI ratios were 0.62 and 0.87, respectively, versus 0.99 in controls (P<0.001 and P<0.001, respectively); mean FA decreases were 67.5% and 40.1%, respectively, compared with a 6.1% increase in controls (P=0.002 and P=0.019, respectively). Mean myelin load decreased by 38.8% (transection) and 51.8% (hemisection) compared to controls (99.1%) (P<0.001 and P<0.001, respectively). Pearson’s correlation coefficients were -0.94 for MEMRI ratio and FA changes and 0.87 for MEMRI and myelin load. Conclusion: MEMERI results correlated to SCI severity measured by FA and myelin load. MEMRI is a useful noninvasive tool to assess neuronal damage after SCI.

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Local Serpin Treatment via Chitosan-Collagen Hydrogel after Spinal Cord Injury Reduces Tissue Damage and Improves Neurologic Function

Journal of Clinical Medicine ◽

10.3390/jcm9041221 ◽

2020 ◽

Vol 9 (4) ◽

pp. 1221 ◽

Cited By ~ 3

Author(s):

Jacek M. Kwiecien ◽

Liqiang Zhang ◽

Jordan R. Yaron ◽

Lauren N. Schutz ◽

Christian J. Kwiecien-Delaney ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Tissue Damage ◽

Low Dose ◽

Dorsal Column ◽

Neurological Deficits ◽

Sustained Delivery ◽

Post Surgery ◽

Cord Injury ◽

Anti Inflammatory

Spinal cord injury (SCI) results in massive secondary damage characterized by a prolonged inflammation with phagocytic macrophage invasion and tissue destruction. In prior work, sustained subdural infusion of anti-inflammatory compounds reduced neurological deficits and reduced pro-inflammatory cell invasion at the site of injury leading to improved outcomes. We hypothesized that implantation of a hydrogel loaded with an immune modulating biologic drug, Serp-1, for sustained delivery after crush-induced SCI would have an effective anti-inflammatory and neuroprotective effect. Rats with dorsal column SCI crush injury, implanted with physical chitosan-collagen hydrogels (CCH) had severe granulomatous infiltration at the site of the dorsal column injury, which accumulated excess edema at 28 days post-surgery. More pronounced neuroprotective changes were observed with high dose (100 µg/50 µL) Serp-1 CCH implanted rats, but not with low dose (10 µg/50 µL) Serp-1 CCH. Rats treated with Serp-1 CCH implants also had improved motor function up to 20 days with recovery of neurological deficits attributed to inhibition of inflammation-associated tissue damage. In contrast, prolonged low dose Serp-1 infusion with chitosan did not improve recovery. Intralesional implantation of hydrogel for sustained delivery of the Serp-1 immune modulating biologic offers a neuroprotective treatment of acute SCI.

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White matter regeneration induced by aligned fibrin nanofiber hydrogel contributes to motor functional recovery in canine T12 spinal cord injury

Regenerative Biomaterials ◽

10.1093/rb/rbab069 ◽

2021 ◽

Author(s):

Zheng Cao ◽

Weitao Man ◽

Yuhui Xiong ◽

Yi Guo ◽

Shuhui Yang ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

White Matter ◽

Nerve Regeneration ◽

Spinal Cord Injuries ◽

Diffusion Tensor ◽

Nerve Fibers ◽

Functional Restoration ◽

Large Animal ◽

Cord Injury

Abstract A hierarchically aligned fibrin hydrogel (AFG) that possesses soft stiffness and aligned nanofiber structure has been successfully proven to facilitate neuroregeneration in vitro and in vivo. However, its potential in promoting nerve regeneration in large animal models that is critical for clinical translation has not been sufficiently specified. Here, the effects of AFG on directing neuroregeneration in canine hemisected T12 spinal cord injuries were explored. Histologically obvious white matter regeneration consisting of a large area of consecutive, compact, and aligned nerve fibers is induced by AFG, leading to a significant motor functional restoration. The canines with AFG implantation start to stand well with their defective legs from 3 to 4 weeks postoperatively and even effortlessly climb the steps from 7 to 8 weeks. Moreover, high-resolution multi-shot diffusion tensor imaging illustrates the spatiotemporal dynamics of nerve regeneration rapidly crossing the lesion within 4 weeks in the AFG group. Our findings indicate that AFG could be a potential therapeutic vehicle for spinal cord injury by inducing rapid white matter regeneration and restoring locomotion, pointing out its promising prospect in clinic practice.

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Longitudinal changes in DTI parameters of specific spinal white matter tracts correlate with behavior following spinal cord injury in monkeys

Scientific Reports ◽

10.1038/s41598-020-74234-2 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Arabinda Mishra ◽

Feng Wang ◽

Li Min Chen ◽

John C. Gore

Keyword(s):

Spinal Cord ◽

White Matter ◽

Spinal Cord Injuries ◽

Diffusion Tensor ◽

Cervical Spinal Cord ◽

Human Subjects ◽

Realistic Model ◽

White Matter Tracts ◽

Injured Side ◽

Cord Injury

Abstract This study aims to evaluate how parameters derived from diffusion tensor imaging reflect axonal disruption and demyelination in specific white matter tracts within the spinal cord of squirrel monkeys following traumatic injuries, and their relationships to function and behavior. After a unilateral section of the dorsal white matter tract of the cervical spinal cord, we found that both lesioned dorsal and intact lateral tracts on the lesion side exhibited prominent disruptions in fiber orientation, integrity and myelination. The degrees of pathological changes were significantly more severe in segments below the lesion than above. The lateral tract on the opposite (non-injured) side was minimally affected by the injury. Over time, RD, FA, and AD values of the dorsal and lateral tracts on the injured side closely tracked measurements of the behavioral recovery. This unilateral section of the dorsal spinal tract provides a realistic model in which axonal disruption and demyelination occur together in the cord. Our data show that specific tract and segmental FA and RD values are sensitive to the effects of injury and reflect specific behavioral changes, indicating their potential as relevant indicators of recovery or for assessing treatment outcomes. These observations have translational value for guiding future studies of human subjects with spinal cord injuries.

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Rat Spinal Cord Injury Experimental Model

Folia Veterinaria ◽

10.1515/fv-2016-0017 ◽

2016 ◽

Vol 60 (2) ◽

pp. 41-46 ◽

Cited By ~ 2

Author(s):

I. Šulla ◽

V. Balik ◽

J. Petrovičová ◽

V. Almášiová ◽

K. Holovská ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Spinal Cord Injuries ◽

Basic Research ◽

Experimental Models ◽

Neurological Deficits ◽

Survival Times ◽

Cord Injury ◽

Female Wistar Rats ◽

Trauma Model

Abstract Spinal cord injuries (SCI) with their tragic consequences belong to the most serious pathological conditions. That is why they have stimulated basic research workers, as well as health care practitioners, to search for an effective treatment for decades. Animal experimental models have been essential in these efforts. We have jointly decided to test and standardize one of the spinal cord injury compression models in rats. Twentythree adult female Wistar rats weighing 250-320 g were utilized. Employing general anaesthesia along with a mixture of sevoflurane with O2, 2 rats (sham controls) had their vertebral arch of either Th8 or Th9 vertebra removed (laminectomy). The other 21 experimental rats with similar laminectomies were divided into 3 subgroups (n = 7) which received compression impact forces of 30, 40 or 50 g (subgroups-1, -2, and -3, respectively) applied on their exposed spinal medulla for 15 minutes. All rats were observed for 28 days after the experimental procedure and their motor functions were assessed by the Basso, Beattie, Bresnahan (BBB) test 6 hours, 7, 21 and 28 days after the simulated SCI. All 23 rats survived the surgical procedures. The control rats were without any neurological deficits. There were, in every experimental subgroup, 1 or 2 rats with extreme BBB scores. So the rats with the maximum and minimum BBB values were excluded. Then, the results acquired in the residual 5 rats in each group were averaged and statistically analysed by the Tukey multiple comparisons test. Statistically significant intersubgroup differences were found at all survival times equal to or longer than 7 post SCI days. The goal of the SCI experiment was to generate a reproducible and reliable, submaximal spinal cord trauma model. The statistical analyses demonstrated that this objective was best achieved in the subgroup-2 with the 40 g compression.

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Modeling spinal cord injuries: advantages and disadvantages

Pediatric Traumatology Orthopaedics and Reconstructive Surgery ◽

10.17816/ptors34638 ◽

2021 ◽

Vol 8 (4) ◽

pp. 485-494

Author(s):

Sergey V. Vissarionov ◽

Timofey S. Rybinskikh ◽

Marat S. Asadulaev ◽

Nikita O. Khusainov

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Clinical Practice ◽

Spinal Cord Injuries ◽

Experimental Models ◽

Laboratory Animals ◽

Severe Injuries ◽

Experimental Animals ◽

Advantages And Disadvantages ◽

Cord Injury

Background. Spinal cord injuries have diverse characteristics and associated traumatic changes; they are known as the most severe injuries of locomotorium. The creation of an optimal experimental model of spinal cord injuries using experimental animals, which would have similar changes in humans, is important to assess and analyze the pathological processes, as well as to develop complex treatment methods. Aim. This study aimed to analyze various experimental models of spinal cord injury using laboratory animals by assessing its advantages and disadvantages for further research and implementation in clinical practice. Materials and methods. A literature review was performed on the capabilities of experimental models of traumatic spinal cord injury in laboratory animals. A literature search was carried out using databases of PubMed, Science Direct, E-library, and Google Scholar for the period from 1981 to 2019; the keywords are shown below. In total, 105 foreign and 37 domestic articles were identified, 59 articles were analyzed after exclusion, and 75% of studies were published in the last 20 years. Results. The review of available experimental options of spinal cord injury in laboratory animals revealed that a generally accepted universal model is not yet established. The experimental animal models had characteristics that do not correspond to the same parameters in an actual clinical situation. Besides, some difficulties were encountered in the estimation of pathological processes of experimental animals, translations with clinical changes, and interpretations of achieved functional results in experimental animals, which complicated the application in clinical practice. Conclusion. Development of experimental models of spinal cord injury that can consider multifactorial aspects of the trauma process, including its biomechanics and time factor, is necessary.

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NT3-chitosan enables de novo regeneration and functional recovery in monkeys after spinal cord injury

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1804735115 ◽

2018 ◽

Vol 115 (24) ◽

pp. E5595-E5604 ◽

Cited By ~ 35

Author(s):

Jia-Sheng Rao ◽

Can Zhao ◽

Aifeng Zhang ◽

Hongmei Duan ◽

Peng Hao ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Motor Neurons ◽

Functional Recovery ◽

De Novo ◽

Diffusion Tensor ◽

Neural Regeneration ◽

Thoracic Spinal Cord ◽

Thoracic Spinal ◽

Cord Injury

Spinal cord injury (SCI) often leads to permanent loss of motor, sensory, and autonomic functions. We have previously shown that neurotrophin3 (NT3)-loaded chitosan biodegradable material allowed for prolonged slow release of NT3 for 14 weeks under physiological conditions. Here we report that NT3-loaded chitosan, when inserted into a 1-cm gap of hemisectioned and excised adult rhesus monkey thoracic spinal cord, elicited robust axonal regeneration. Labeling of cortical motor neurons indicated motor axons in the corticospinal tract not only entered the injury site within the biomaterial but also grew across the 1-cm-long lesion area and into the distal spinal cord. Through a combination of magnetic resonance diffusion tensor imaging, functional MRI, electrophysiology, and kinematics-based quantitative walking behavioral analyses, we demonstrated that NT3-chitosan enabled robust neural regeneration accompanied by motor and sensory functional recovery. Given that monkeys and humans share similar genetics and physiology, our method is likely translatable to human SCI repair.

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Recurrent spinal cord injury without radiographic abnormalities in children

Journal of Neurosurgery ◽

10.3171/jns.1988.69.2.0177 ◽

1988 ◽

Vol 69 (2) ◽

pp. 177-182 ◽

Cited By ~ 55

Author(s):

Ian F. Pollack ◽

Dachling Pang ◽

Robert Sclabassi

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Soft Tissues ◽

Spinal Cord Injuries ◽

Dorsal Column ◽

Neurological Deficits ◽

Spinal Instability ◽

Content Type ◽

Flexion Extension ◽

Cord Injury

✓ Spinal cord injury without radiographic abnormality is a well-known entity in the pediatric age group. Agerelated elasticity of the vertebral ligaments as well as immaturity of the osseous structures in the pediatric spine allow momentary subluxation in response to deforming forces. The resultant neurological injuries range from transient dorsal column dysfunction to complete cord transection. Between 1960 and 1985, 42 such injuries were treated at the Children's Hospital of Pittsburgh. Management of these radiographically occult spinal cord injuries consisted of cervical immobilization for 2 months in a hard collar and restriction of contact sports. Recurrent cord injury occurred in eight cases during the 2-month immobilization period. A clearly defined traumatic episode was identified in seven of the eight patients, although in four children the recurrent trauma to the spine was trivial. Five of the children removed their collars briefly before the second injury, and two children incurred reinjury with the hard collar in place. The remaining child was too young for hard-collar immobilization, and recurrent neurological deterioration occurred during sleep. Serial flexion-extension films failed to detect frank instability in any of the eight cases. The children most susceptible to reinjury were those who sustained mild or transient neurological deficits from an initial cord injury and who rapidly resumed normal activities. Radiographically occult spinal instability resulting from the initial injury to the vertebral and paravertebral soft tissues presumably made these children vulnerable to recurrent spinal cord injury, often from otherwise insignificant trauma. During the last 21 months, 12 additional children have been managed with a more stringent protocol combining neck immobilization in a rigid cervical brace for 3 months and restriction of both contact and noncontact sports, together with a major emphasis on patient compliance. With this new protocol, no recurrent cord injuries have been documented.

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Impairment Rating and Spinal Cord Injuries: Revisiting the Guides

Guides Newsletter ◽

10.1001/amaguidesnewsletters.2010.mayjun01 ◽

2010 ◽

Vol 15 (3) ◽

pp. 1-7

Author(s):

Richard T. Katz

Keyword(s):

Spinal Cord ◽

Spinal Cord Injuries ◽

Functional Independence ◽

Outcome Data ◽

Multiple Organ ◽

Loss Of Function ◽

Sixth Edition ◽

Organ Systems ◽

Cord Injury ◽

Impairment Ratings

Abstract This article addresses some criticisms of the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides) by comparing previously published outcome data from a group of complete spinal cord injury (SCI) persons with impairment ratings for a corresponding level of injury calculated using the AMA Guides, Sixth Edition. Results of the comparison show that impairment ratings using the sixth edition scale poorly with the level of impairments of activities of daily living (ADL) in SCI patients as assessed by the Functional Independence Measure (FIM) motor scale and the extended FIM motor scale. Because of the combinations of multiple impairments, the AMA Guides potentially overrates the impairment of paraplegics compared with that of quadriplegics. The use and applicability of the Combined Values formula should be further investigated, and complete loss of function of two upper extremities seems consistent with levels of quadriplegia using the SCI model. Some aspects of the AMA Guides contain inconsistencies. The concept of diminishing impairment values is not easily translated between specific losses of function per organ system and “overall” loss of ADLs involving multiple organ systems, and the notion of “catastrophic thresholds” involving multiple organ systems may support the understanding that variations in rating may exist in higher rating cases such as those that involve an SCI.

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