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Levetiracetam treatment leads to functional recovery after thoracic or cervical injuries of the spinal cord.

ABSTRACT: Spinal cord injury (SCI) leads to dramatic impairments of motor, sensory, and autonomic functions of affected individuals. Following the primary injury, there is an increased release of glutamate that leads to excitotoxicity and further neuronal death. Therefore, modulating glutamate excitotoxicity seems to be a promising target to promote neuroprotection during the acute phase of the injury. In this study, we evaluated the therapeutic effect of a FDA approved antiepileptic drug (levetiracetam-LEV), known for binding to the synaptic vesicle protein SV2A in the brain and spinal cord. LEV therapy was tested in two models of SCI-one affecting the cervical and other the thoracic level of the spinal cord. The treatment was effective on both SCI models. Treated animals presented significant improvements on gross and fine motor functions. The histological assessment revealed a significant decrease of cavity size, as well as higher neuronal and oligodendrocyte survival on treated animals. Molecular analysis revealed that LEV acts by stabilizing the astrocytes allowing an effective uptake of the excess glutamate from the extracellular space. Overall, our results demonstrate that Levetiracetam may be a promising drug for acute management of SCI.

SUBMITTER: Lima R

PROVIDER: S-EPMC7977146 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Levetiracetam treatment leads to functional recovery after thoracic or cervical injuries of the spinal cord.

Lima Rui R Gomes Eduardo D ED Cibrão Jorge R JR Rocha Luís A LA Assunção-Silva Rita C RC Rodrigues Cláudia S CS Neves-Carvalho Andreia A Monteiro Susana S Salgado António J AJ Silva Nuno A NA

NPJ Regenerative medicine 20210302 1

Spinal cord injury (SCI) leads to dramatic impairments of motor, sensory, and autonomic functions of affected individuals. Following the primary injury, there is an increased release of glutamate that leads to excitotoxicity and further neuronal death. Therefore, modulating glutamate excitotoxicity seems to be a promising target to promote neuroprotection during the acute phase of the injury. In this study, we evaluated the therapeutic effect of a FDA approved antiepileptic drug (levetiracetam-L ...[more]

PMID: 33654068

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Project description:BackgroundRollover crashes continue to be a substantial public health issue in North America. Previous research has shown that the cervical spine is the most injured spine segment in rollovers, but much of the past research has focused on risk factors rather than the actual cervical spine injuries. We sought to examine how different types of cervical spine injuries (vertebral and/or cord injury) vary with different occupant-related factors in rollovers and to compare these with non-rollovers.MethodsWe obtained crash and injury information from the National Automotive Sampling System-Crashworthiness Data System (NASS-CDS) for 2005-2015 and Crash Investigation Sampling System (CISS) for 2017-2022. Based on weighted data, we calculated relative risks to assess how occupant sex, seat belt use, ejection status, and fatal outcome relate to the rate of different cervical spine injuries in rollovers and non-rollovers.ResultsIn NASS-CDS occupants with cervical spine injuries (N = 111,040 weighted cases), about 91.5% experienced at least one vertebral injury whereas only 11.3% experienced a spinal cord injury (most of which had a concomitant vertebral fracture). All types of cervical spine injuries we examined were 3.4-5.2 times more likely to occur in rollovers compared to non-rollovers. These relative risks were similar for both sexes, belted and unbelted, non-ejected, and non-fatal occupants. The number of weighted CISS occupants with cervical spine injuries (N = 42,003) was smaller than in the NASS analysis, but cervical spine injuries remained 6.25 to 6.36 times more likely in rollovers compared to non-rollovers despite a more modern vehicle fleet.ConclusionsThese findings underscore the continued need for rollover-specific safety countermeasures, especially those focused on cervical spine injury prevention, and elucidate the frequency, severity and other characteristics of the specific vertebral and spinal cord injuries being sustained in rollovers. Our findings suggest that countermeasures focused on preventing cervical vertebral fractures will also effectively prevent most cervical spinal cord injuries.

Project description:The number of elderly patients with spinal cord injury without radiographic abnormalities (SCIWORA) has been increasing in recent years and common of most cervical spinal cord injuries. Basic research has shown the effectiveness of early decompression after spinal cord injury on the spinal cord without stenosis; no studies have reported the efficacy of decompression in models with spinal cord compressive lesions. The purpose of this study was to evaluate the effects of decompression surgery after acute spinal cord injury in rats with chronic spinal cord compressive lesions, mimicking SCIWORA. A water-absorbent polymer sheet (Aquaprene DX, Sanyo Chemical Industries) was inserted dorsally into the 4-5th cervical sublaminar space in 8-week-old Sprague Dawley rats to create a rat model with a chronic spinal compressive lesion. At the age of 16 weeks, 30 mildly myelopathic or asymptomatic rats with a Basso, Beattie, and Bresnahan score (BBB score) of 19 or higher were subjected to spinal cord compression injuries. The rats were divided into three groups: an immediate decompression group (decompress immediately after injury), a sub-acute decompression group (decompress 1 week after injury), and a non-decompression group. Behavioral and histological evaluations were performed 4 weeks after the injury. At 20 weeks of age, the BBB score and FLS (Forelimb Locomotor Scale) of both the immediate and the sub-acute decompression groups were significantly higher than those of the non-decompression group. There was no significant difference between the immediate decompression group and the sub-acute decompression group. TUNEL (transferase-mediated dUTP nick end labeling) staining showed significantly fewer positive cells in both decompression groups compared to the non-decompression group. LFB (Luxol fast blue) staining showed significantly more demyelination, and GAP-43 (growth associated protein-43) staining tended to show fewer positive cells in the non-decompression group. Decompression surgery in the acute or sub-acute phase of injury is effective after mild spinal cord injury in rats with chronic compressive lesions. There was no significant difference between the immediate decompression and sub-acute decompression groups.

Project description:Study designMonocenter case-control study.ObjectiveEffects of spinal surgical adverse events (SSAE) on clinical and functional outcome, length of stay, and treatment costs after traumatic cervical spinal cord injury (SCI).Summary of background dataTraumatic SCI is a challenge for primary care centers because of the emergency setting and complex injury patterns. SSAE rates of up to 15% are reported for spine fractures without SCI. Little is known about SSAE after traumatic SCI and their outcome relevance.MethodsAcute traumatic cervical SCI patients were enrolled from 2011 to 2017. Cases with and without SSAE were compared regarding neurological recovery, functional outcome, secondary complications, mortality, length of stay, and treatment costs. Adjusted logistic regression and generalized estimating equation models were calculated for the endpoints ASIA impairment scale (AIS)-conversion and dysphagia. All analyses were run in the total and in a propensity score matched sample.ResultsAt least one SSAE occurred in 37 of 165 patients (22.4%). Mechanical instability and insufficient spinal decompression were the most frequent SSAE with 13 (7.9%) or 11 (6.7%) cases, respectively. The regression models adjusted for demographic, injury, and surgery characteristics demonstrated a reduced probability for AIS-conversion related to SSAE (OR [95% CI] 0.14 [0.03-0.74]) and additionally to single-sided ventral or dorsal surgical approach (0.12 [0.02-0.69]) in the matched sample. Furthermore, SSAE were associated with higher risk for dysphagia in the matched (4.77 [1.31-17.38]) and the total sample (5.96 [2.07-17.18]). Primary care costs were higher in cases with SSAE (median (interquartile range) 97,300 [78,200-112,300]) EUR compared with cases without SSAE (52,300 [26,700-91,200]) EUR.ConclusionSSAE are an important risk factor after acute traumatic cervical SCI with impact on neurological recovery, functional outcome, and healthcare costs. Reducing SSAE is a viable means to protect the limited intrinsic capacity for recovery from SCI.Level of Evidence: 4.

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Levetiracetam treatment leads to functional recovery after thoracic or cervical injuries of the spinal cord.

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Levetiracetam treatment leads to functional recovery after thoracic or cervical injuries of the spinal cord.

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