Levetiracetam treatment leads to functional recovery after thoracic or cervical injuries of the spinal cord.
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ABSTRACT:
SUBMITTER: Lima R
PROVIDER: S-EPMC7977146 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Spinal cord injury (SCI) is a severe condition leading to enduring motor deficits. When lesions are incomplete, promoting spinal cord plasticity might be a useful strategy to elicit functional recovery. Here we investigated whether long-term fluoxetine administration in the drinking water, a treatment recently demonstrated to optimize brain plasticity in several pathological conditions, promotes motor recovery in rats that received a C4 dorsal funiculus crush. We show that fluoxetine administration markedly improved motor functions compared to controls in several behavioral paradigms. The improved functional effects correlated positively with significant sprouting of intact corticospinal fibers and a modulation of the excitation/inhibition balance. Our results suggest a potential application of fluoxetine treatment as a non invasive therapeutic strategy for SCI-associated neuropathologies.
| S-EPMC3713566 | biostudies-literature
Project description:ObjectivesTo describe functional and structural impairments of the pulmonary system in middle-aged people with cervical and upper thoracic spinal cord injuries (SCI), and compare findings to the general population. To determine if the neurological level of injury (NLI) is related to functional and structural impairments, and if age is related to structural impairments.DesignCross-sectional study with matched controls. Data from the Swedish SPinal Cord Injury Study on Cardiopulmonary and Autonomic Impairment (SPICA). Matched control data were obtained from the Swedish CArdioPulmonary bioImage Study (SCAPIS).SettingOutpatient SCI unit in southern Sweden.Participants25 people (20% women, mean age 58 years, mean time since injury 28 years, NLIs C2-T6, American Spinal Injury Association Impairment Scale A-C).InterventionsNot applicable.Outcome measuresLung function was assessed with spirometry, diffusing capacity and impulse oscillometry. Structural assessments were performed with computed tomography.ResultsPulmonary function was generally worse compared to the controls. Structural impairments were common (75% of the participants and 65% of the controls; P = 0.36, NS). NLI was significantly related to some of the functional and structural impairments.ConclusionsMiddle-aged people with long-term cervical and upper thoracic SCI can have substantial pulmonary functional impairments, whereas structural impairments do not differ considerably from the general population. Further larger and longitudinal studies should focus on the clinical impact of these impairments over time.
| S-EPMC10446799 | biostudies-literature
Project description:Previously, we and others have shown that rodent neural progenitor cells (NPCs) can support functional recovery after cervical and thoracic transection injuries. To extend these observations to a more clinically relevant model of spinal cord injury, we performed unilateral midcervical contusion injuries in Fischer 344 rats. Two-weeks later, E14-derived syngeneic spinal cord-derived multi-potent NPCs were implanted into the lesion cavity. Control animals received either no grafts or fibroblast grafts. The NPCs differentiated into all three neural lineages (neurons, astrocytes, oligodendrocytes) and robustly extended axons into the host spinal cord caudal and rostral to the lesion. Graft-derived axons grew into host gray matter and expressed synaptic proteins in juxtaposition with host neurons. Animals that received NPC grafts exhibited significant recovery of forelimb motor function compared with the two control groups (analysis of variance p?<?0.05). Thus, NPC grafts improve forelimb motor outcomes after clinically relevant cervical contusion injury. These benefits are observed when grafts are placed two weeks after injury, a time point that is more clinically practical than acute interventions, allowing time for patients to stabilize medically, simplifying enrollment in clinical trials, and enhancing predictability of spontaneous improvement in control groups.
| S-EPMC5908429 | biostudies-literature
Project description:BackgroundSpinal cord injury is a major cause of long-term disability and has no current clinically accepted treatment. Leptin, an adipocyte-derived hormone, is best known as a regulator of food intake and energy expenditure. Interestingly, several studies have demonstrated that leptin has significant effects on proliferation and cell survival in different neuropathologies. Here, we sought to evaluate the role of leptin after spinal cord injury.FindingsBased on its proposed neuroprotective role, we have evaluated the effects of a single, acute intraparenchymal injection of leptin in a clinically relevant animal model of spinal cord injury. As determined by quantitative Real Time-PCR, endogenous leptin and the long isoform of the leptin receptor genes show time-dependent variations in their expression in the healthy and injured adult spinal cord. Immunohistochemical analysis of post-injury tissue showed the long isoform of the leptin receptor expression in oligodendrocytes and, to a lesser extent, in astrocytes, microglia/macrophages and neurons. Moreover, leptin administered after spinal cord injury increased the expression of neuroprotective genes, reduced caspase-3 activity and decreased the expression of pro-inflammatory molecules. In addition, histological analysis performed at the completion of the study showed that leptin treatment reduced microglial reactivity and increased caudal myelin preservation, but it did not modulate astroglial reactivity. Consequently, leptin improved the recovery of sensory and locomotor functioning.ConclusionsOur data suggest that leptin has a prominent neuroprotective and anti-inflammatory role in spinal cord damage and highlights leptin as a promising therapeutic agent.
| S-EPMC3334982 | biostudies-literature
Project description:Previous studies suggest locomotion training could be an effective non-invasive therapy after spinal cord injury (SCI) using primarily acute thoracic injuries. However, the majority of SCI patients have chronic cervical injuries. Regaining hand function could significantly increase their quality of life. In this study, we used a clinically relevant chronic cervical contusion to study the therapeutic efficacy of rehabilitation in forelimb functional recovery. Nude rats received a moderate C5 unilateral contusive injury and were then divided into two groups with or without Modified Montoya Staircase (MMS) rehabilitation. For the rehabilitation group, rats were trained 5 days a week starting at 8 weeks post-injury (PI) for 6 weeks. All rats were assessed for skilled forelimb functions with MMS test weekly and for untrained gross forelimb locomotion with grooming and horizontal ladder (HL) tests biweekly. Our results showed that MMS rehabilitation significantly increased the number of pellets taken at 13 and 14 weeks PI and the accuracy rates at 12 to 14 weeks PI. However, there were no significant differences in the grooming scores or the percentage of HL missteps at any time point. Histological analyses revealed that MMS rehabilitation significantly increased the number of serotonergic fibers and the amount of presynaptic terminals around motor neurons in the cervical ventral horns caudal to the injury and reduced glial fibrillary acidic protein (GFAP)-immunoreactive astrogliosis in spinal cords caudal to the lesion. This study shows that MMS rehabilitation can modify the injury environment, promote axonal sprouting and synaptic plasticity, and importantly, improve reaching and grasping functions in the forelimb, supporting the therapeutic potential of task-specific rehabilitation for functional recovery after chronic SCI.
| S-EPMC7266985 | biostudies-literature
Project description:Serotonergic agents can improve the recovery of motor ability after a spinal cord injury. Herein, we compare the effects of buspirone, a 5-HT1A receptor partial agonist, to fluoxetine, a selective serotonin reuptake inhibitor, on forelimb motor function recovery after a C4 bilateral dorsal funiculi crush in adult female rats. After injury, single pellet reaching performance and forelimb muscle activity decreased in all rats. From 1 to 6 weeks after injury, rats were tested on these tasks with and without buspirone (1-2 mg/kg) or fluoxetine (1-5 mg/kg). Reaching and grasping success rates of buspirone-treated rats improved rapidly within 2 weeks after injury and plateaued over the next 4 weeks of testing. Electromyography (EMG) from selected muscles in the dominant forelimb showed that buspirone-treated animals used new reaching strategies to achieve success after the injury. However, forelimb performance dramatically decreased within 2 weeks of buspirone withdrawal. In contrast, fluoxetine treatment resulted in a more progressive rate of improvement in forelimb performance over 8 weeks after injury. Neither buspirone nor fluoxetine significantly improved quadrupedal locomotion on the horizontal ladder test. The improved accuracy of reaching and grasping, patterns of muscle activity, and increased excitability of spinal motor-evoked potentials after buspirone administration reflect extensive reorganization of connectivity within and between supraspinal and spinal sensory-motor netxcopy works. Thus, both serotonergic drugs, buspirone and fluoxetine, neuromodulated these networks to physiological states that enabled markedly improved forelimb function after cervical spinal cord injury.
| S-EPMC8423890 | biostudies-literature
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.
| S-EPMC9402533 | biostudies-literature
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.
| S-EPMC8654254 | biostudies-literature
Project description:Traumatic human spinal cord injury (SCI) causes devastating and long-term hardships. These are due to the irreparable primary mechanical injury and secondary injury cascade. In particular, oligodendrocyte cell death, white matter axon damage, spared axon demyelination, and the ensuing dysfunction in action potential conduction lead to the initial deficits and impair functional recovery. For these reasons, and that oligodendrocyte and axon survival may be related, various neuroprotective strategies after spinal cord injury are being investigated. We previously demonstrated that oligodendrocytes in the adult rat epicenter ventrolateral funiculus (VLF) express 3'-5'-cyclic adenosine monophosphate-dependent phosphodiesterase 4 (PDE4) subtypes and that their death was attenuated up to 3 days after contusive cervical SCI when rolipram, a specific inhibitor of PDE4, was administered. Here, we report that (1) there are more oligodendrocyte somata in the adult rat epicenter VLF, (2) descending and ascending axonal conductivity in the VLF improves, and that (3) there are fewer hindlimb footfall errors during grid-walking at 5 weeks after contusive cervical SCI when rolipram is delivered for 2 weeks. This is the first demonstration of improved descending and ascending long-tract axonal conductivity across a SCI with this pharmacological approach. Since descending long-tract axonal conductivity did not return to normal, further evaluations of the pharmacokinetics and therapeutic window of rolipram as well as optimal combinations are necessary before consideration for neuroprotection in humans with SCI.
| S-EPMC2760664 | biostudies-literature
Project description:With no currently available drug treatment for spinal cord injury, there is a need for additional therapeutic candidates. We took the approach of repositioning existing pharmacological agents to serve as acute treatments for spinal cord injury and previously found imatinib to have positive effects on locomotor and bladder function in experimental spinal cord injury when administered immediately after the injury. However, for imatinib to have translational value, it needs to have sustained beneficial effects with delayed initiation of treatment, as well. Here, we show that imatinib improves hind limb locomotion and bladder recovery when initiation of treatment was delayed until 4?h after injury and that bladder function was improved with a delay of up to 24?h. The treatment did not induce hypersensitivity. Instead, imatinib-treated animals were generally less hypersensitive to either thermal or mechanical stimuli, compared with controls. In an effort to provide potential biomarkers, we found serum levels of three cytokines/chemokines--monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-3?, and keratinocyte chemoattractant/growth-regulated oncogene (interleukin 8)--to increase over time with imatinib treatment and to be significantly higher in injured imatinib-treated animals than in controls during the early treatment period. This correlated to macrophage activation and autofluorescence in lymphoid organs. At the site of injury in the spinal cord, macrophage activation was instead reduced by imatinib treatment. Our data strengthen the case for clinical trials of imatinib by showing that initiation of treatment can be delayed and by identifying serum cytokines that may serve as candidate markers of effective imatinib doses.
| S-EPMC4752188 | biostudies-literature