Coexistence of chronic hyperalgesia and multilevel neuroinflammatory responses after experimental SCI: a systematic approach to profiling neuropathic pain

Wang, Lei; Gunduz, Mehmet A.; Semeano, Ana T.; Yılmaz, Enis C.; Alanazi, Feras A. H.; Imir, Ozan B.; Yener, Ulaş; Arbelaez, Christian; Usuga, Esteban; Teng, Yang D.

doi:10.1186/s12974-022-02628-2

Cited by 6 publications

(12 citation statements)

References 116 publications

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“…In particular, VitD modulated inflammatory response in CNS and immune systems ( 83 ). Future researchers should elucidate the exact effect of VitD in the systematic inflammation and neuroinflammation after SCI ( 84 ). Furthermore, VitD can enhance neural stem cell proliferation and differentiation into neurons and oligodendrocytes ( 85 , 86 ).…”

Section: Discussionmentioning

confidence: 99%

Impact of vitamin D on the prognosis after spinal cord injury: A systematic review

Wang

Gan²,

Wu³

et al. 2023

Front. Nutr.

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Vitamin D (VitD) insufficiency is a worldwide health problem and affects billions of people. Spinal cord injury (SCI) patients seem more susceptible to developing suboptimal levels of VitD. However, the literature regarding its impact on the prognosis of SCI is limited. Thus, in this review, we systematically investigated the published studies via a combination of keywords associated with SCI and VitD in four medical databases (Medline, Embase, Scopus, and Web of Science). All included studies were analyzed, and selected clinical data on the prevalence of VitD insufficiency (serum 25-hydroxyvitamin D < 30 ng/ml) and deficiency (serum 25-hydroxyvitamin D < 20 ng/ml) were collected for further meta-analysis via random effects. Through literature review, a total of 35 studies were eligible and included. The meta-analysis of VitD status (13 studies, 1,962 patients) indicated high prevalence of insufficiency (81.6% [75.7, 87.5]) and deficiency (52.5% [38.1, 66.9]) after SCI. Besides, low levels of VitD were reported to be associated with a higher risk of skeletal diseases, venous thromboembolism, psychoneurological syndromes, and chest illness after injury. Existing literature suggested that supplemental therapy might act as an adjuvant treatment to facilitate post-injury rehabilitation. Non-human experimental studies highlighted the neuroprotective effect of VitD, which was associated with enhancing axonal and neuronal survival, suppressing neuroinflammation, and modulating autophagy. Therefore, the current evidence suggests that the prevalence of VitD insufficiency is high in the SCI population, and low-level VitD may impair functional restoration after SCI. VitD supplemental treatment may have potential benefits to accelerate rehabilitation in mechanistically related processes after SCI. However, due to the limitation of the available evidence, more well-designed randomized controlled trials and mechanism experimental research are still needed to validate its therapeutic effect, elucidate its neuroprotective mechanism, and develop novel treatments.

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Section: Discussionmentioning

confidence: 99%

Impact of vitamin D on the prognosis after spinal cord injury: A systematic review

Wang

Gan²,

Wu³

et al. 2023

Front. Nutr.

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“…The bladders of SCI rats were evacuated twice daily until a "reflex bladder" was established, usually around 5-9 days p.i. [24][25][26]. (2) Comparison between NT sami and NT samo vs. SCI mi and SCI mo , respectively, was justified as earlier work showed no significant impact of a similar EEE housing formula on subacute NT for SCI rats [19].…”

Section: Animals Sci Modeling and Perioperative Managementmentioning

confidence: 99%

“…(2) The incline plane test: This test measures the animal's ability to maintain stable body position when positioned head-up and head-down (i.e., the rostrocaudal axis of the trunk is parallel to the longitudinal axis of the plane). The functional status was quantified by the highest angle of incline at which an animal could maintain its posture for 5 s [23,26].…”

Section: Behavioral Evaluationsmentioning

confidence: 99%

T12-L3 Nerve Transfer-Induced Locomotor Recovery in Rats with Thoracolumbar Contusion: Essential Roles of Sensory Input Rerouting and Central Neuroplasticity

Yu,

Zeng,

Aljuboori

et al. 2023

Cells

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Locomotor recovery after spinal cord injury (SCI) remains an unmet challenge. Nerve transfer (NT), the connection of a functional/expendable peripheral nerve to a paralyzed nerve root, has long been clinically applied, aiming to restore motor control. However, outcomes have been inconsistent, suggesting that NT-induced neurological reinstatement may require activation of mechanisms beyond motor axon reinnervation (our hypothesis). We previously reported that to enhance rat locomotion following T13-L1 hemisection, T12-L3 NT must be performed within timeframes optimal for sensory nerve regrowth. Here, T12-L3 NT was performed for adult female rats with subacute (7–9 days) or chronic (8 weeks) mild (SCImi: 10 g × 12.5 mm) or moderate (SCImo: 10 g × 25 mm) T13-L1 thoracolumbar contusion. For chronic injuries, T11-12 implantation of adult hMSCs (1-week before NT), post-NT intramuscular delivery of FGF2, and environmentally enriched/enlarged (EEE) housing were provided. NT, not control procedures, qualitatively improved locomotion in both SCImi groups and animals with subacute SCImo. However, delayed NT did not produce neurological scale upgrading conversion for SCImo rats. Ablation of the T12 ventral/motor or dorsal/sensory root determined that the T12-L3 sensory input played a key role in hindlimb reanimation. Pharmacological, electrophysiological, and trans-synaptic tracing assays revealed that NT strengthened integrity of the propriospinal network, serotonergic neuromodulation, and the neuromuscular junction. Besides key outcomes of thoracolumbar contusion modeling, the data provides the first evidence that mixed NT-induced locomotor efficacy may rely pivotally on sensory rerouting and pro-repair neuroplasticity to reactivate neurocircuits/central pattern generators. The finding describes a novel neurobiology mechanism underlying NT, which can be targeted for development of innovative neurotization therapies.

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“…These treatments rely heavily on the patient's limited capacity to self-repair and rebuild damaged nerve tissue. Stem cell therapy as an alternative strategy has great promise for the treatment of SCI [ 5 ], because stem cells are able to self-renew, differentiate into multiple lineages and secrete neurotrophic factors [ 6 , 7 ] and neuroinflammation [ 8 , 9 ]. Among several types of stem cells evaluated, neural stem cells (NSCs) are of particular interest, as they can replace lost host cells, rebuild neuronal circuitry and lost connectivity, provide nutritional support to promote functional recovery and play other roles in acute SCI [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Combined transplantation of hiPSC-NSC and hMSC ameliorated neuroinflammation and promoted neuroregeneration in acute spinal cord injury

Du,

Kong,

Guo

et al. 2024

Stem Cell Res Ther

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Background Spinal cord injury (SCI) is a serious clinical condition that has pathological changes such as increased neuroinflammation and nerve tissue damage, which eventually manifests as fibrosis of the injured segment and the development of a spinal cord cavity leading to loss of function. Cell-based therapy, such as mesenchymal stem cells (MSCs) and neural stem cells (NSCs) are promising treatment strategies for spinal cord injury via immunological regulation and neural replacement respectively. However, therapeutic efficacy is rare reported on combined transplantation of MSC and NSC in acute mice spinal cord injury even the potential reinforcement might be foreseen. Therefore, this study was conducted to investigate the safety and efficacy of co-transplanting of MSC and NSC sheets into an SCI mice model on the locomotor function and pathological changes of injured spinal cord. Methods To evaluate the therapeutic effects of combination cells, acute SCI mice model were established and combined transplantation of hiPSC-NSCs and hMSCs into the lesion site immediately after the injury. Basso mouse scale was used to perform the open-field tests of hind limb motor function at days post-operation (dpo) 1, 3, 5, and 7 after SCI and every week after surgery. Spinal cord and serum samples were collected at dpo 7, 14, and 28 to detect inflammatory and neurotrophic factors. Hematoxylin–eosin (H&E) staining, masson staining and transmission electron microscopy were used to evaluate the morphological changes, fibrosis area and ultrastructure of the spinal cord. Result M&N transplantation reduced fibrosis formation and the inflammation level while promoting the secretion of nerve growth factor and brain-derived neurotrophic factor. We observed significant reduction in damaged tissue and cavity area, with dramatic improvement in the M&N group. Compared with the Con group, the M&N group exhibited significantly improved behaviors, particularly limb coordination. Conclusion Combined transplantation of hiPSC-NSC and hMSC could significantly ameliorate neuroinflammation, promote neuroregeneration, and decrease spinal fibrosis degree in safe and effective pattern, which would be indicated as a novel potential cell treatment option. Graphical abstract

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Coexistence of chronic hyperalgesia and multilevel neuroinflammatory responses after experimental SCI: a systematic approach to profiling neuropathic pain

Cited by 6 publications

References 116 publications

Impact of vitamin D on the prognosis after spinal cord injury: A systematic review

Impact of vitamin D on the prognosis after spinal cord injury: A systematic review

T12-L3 Nerve Transfer-Induced Locomotor Recovery in Rats with Thoracolumbar Contusion: Essential Roles of Sensory Input Rerouting and Central Neuroplasticity

Combined transplantation of hiPSC-NSC and hMSC ameliorated neuroinflammation and promoted neuroregeneration in acute spinal cord injury

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