Spinal cord stress and strain contribute to degenerative cervical myelopathy (DCM), while cervical kyphosis is known to negatively impact surgical outcomes. In DCM, the relationship between spinal cord biomechanics, sagittal alignment, and cord compression is not well understood. Quantifying this relationship can guide surgical strategies. A previously validated three-dimensional finite element model of the human cervical spine with spinal cord was used. Three models of cervical alignment were created: lordosis (C2-C7 Cobb angle: 20°), straight (0°), and kyphosis (- 9°). C5-C6 spinal stenosis was simulated with ventral disk protrusions, reducing spinal canal diameters to 10 mm, 8 mm, and 6 mm. Spinal cord pre-stress and pre-strain due to alignment and compression were quantified. Cervical flexion and extension were simulated with a pure moment load of 2 Nm. The Von Mises stress and maximum principal strain of the whole spinal cord were calculated during neck motion and the relationship between spinal cord biomechanics, alignment, and compression was analyzed using linear regression analysis. Spinal cord pre-stress and pre-strain were greatest with kyphosis (7.53 kPa, 5.4%). Progressive kyphosis and stenosis were associated with an increase in spinal cord stress (R2 = 0.99) and strain (R2 = 0.99). Cervical kyphosis was associated with greater spinal cord stress and strain during neck flexion-extension and the magnitude of difference increased with increasing stenosis. Cervical kyphosis increases baseline spinal cord stress and strain. Incorporating sagittal alignment with compression to calculate spinal cord biomechanics is necessary to accurately quantify spinal stress and strain during neck flexion and extension.

Intramedullary astrocytomas (IMAs) are the second most frequent intramedullary tumors in adults. Low-grade IMAs (LG-IMA, WHO grade I and II) carry a better prognosis than high-grade IMAs (HG-IMAs). However, adjuvant treatment of LG-IMAs by radiotherapy (RT) and/or chemotherapy (CT) as well as treatment of tumor recurrences remains controversial. The aim of our study was to evaluate the postoperative outcome of LG-IMAs and the management of recurring tumors. We retrospectively reviewed a series of patients operated on for IMA from 1980 to 2022 in a single neurosurgical department. We retrieved 40 patients who received surgery for intramedullary astrocytomas, including 30 LG-IMAs (22 WHO grade I; 5 WHO grade II; 3 \"low-grade\") and 10 HG-IMAs (4 WHO grade III; 5 WHO grade IV; 1 \"high-grade\"). Of the patients with LG-IMAs, the extent of surgical resection was large (gross or subtotal resection >90%) in 30% of cases. Immediate postoperative radiotherapy and/or chemotherapy was proposed only to patients who underwent biopsy (n = 5), while others were initially followed-up. Over a median follow-up of 59 months (range = 13-376), 16 LG-IMA (53.3%) recurred with a mean delay of 28.5 months after surgery (range = 3-288). These included seven biopsies, five partial resections (PR), four subtotal resections (STR) but no gross total resections (GTR). Progression-free survival for LG-IMAs was 51.9% at 3 years and 35.6% at 5 and 10 years; overall survival was 96.3% at 3 years; 90.9% at 5 years and 81.9% at 10 years. There were no significant differences in terms of OS and PFS between WHO grade I and grade II tumors. However, \"large resections\" (GTR or STR), as opposed to \"limited resections\" (PR and biopsies), were associated with both better OS (p = 0.14) and PFS (p = 0.04). The treatment of recurrences consisted of surgery alone (n = 3), surgery with RT and/or CT (n = 2), RT with CT (n = 3), RT alone (n = 2) or CT alone (n = 2). In conclusion, although LG-IMAs are infiltrating tumors, the extent of resection (GTR or STR), but not WHO grading, is the main prognostic factor. The management of recurring tumors is highly variable with no conclusive evidence for either option.

Regulation of neuroinflammation is critical for maintaining central nervous system (CNS) homeostasis and holds therapeutic promise in autoimmune diseases such as multiple sclerosis (MS). Previous studies have highlighted the significance of selective innate signaling in triggering anti-inflammatory mechanisms, which play a protective role in an MS-like disease, experimental autoimmune encephalomyelitis (EAE). However, the individual intra-CNS administration of specific innate receptor ligands or agonists, such as for toll-like receptor 7 (TLR7) and nucleotide-binding oligomerization-domain-containing protein 2 (NOD2), failed to elicit the desired anti-inflammatory response in EAE. In this study, we investigated the potential synergistic effect of targeting both TLR7 and NOD2 simultaneously to prevent EAE progression. Our findings demonstrate that simultaneous intrathecal administration of NOD2- and TLR7-agonists led to synergistic induction of Type I IFN (IFN I) and effectively suppressed EAE in an IFN I-dependent manner. Suppression of EAE was correlated with a significant decrease in the infiltration of monocytes, granulocytes, and natural killer cells, reduced demyelination, and downregulation of IL-1β, CCL2, and IFNγ gene expression in the spinal cord. These results underscore the therapeutic promise of concurrently targeting the TLR7 and NOD2 pathways in alleviating neuroinflammation associated with MS, paving the way for novel and more efficacious treatment strategies.

Two cases of complicated pain exist: posterior screw fixation and myofascial pain. Intramuscular pulsed radiofrequency (PRF) may be an alternative treatment for such patients. This is a two-stage animal study. In the first stage, two muscle groups and two nerve groups were subdivided into a high-temperature group with PRF at 58 °C and a regular temperature with PRF at 42 °C in rats. In the second stage, two nerve injury groups were subdivided into nerve injury with PRF 42 °C on the sciatic nerve and muscle. Blood and spinal cord samples were collected. In the first stage, the immunohistochemical analysis showed that PRF upregulated brain-derived neurotrophic factor (BDNF) in the spinal cord in both groups of rats. In the second stage, the immunohistochemical analysis showed significant BDNF and tropomyosin receptor kinase B (TrkB) expression within the spinal cord after PRF in muscles and nerves after nerve injury. The blood biomarkers showed a significant increase in BDNF levels. PRF in the muscle in rats could upregulate BDNF-TrkB in the spinal cord, similar to PRF on the sciatica nerve for pain relief in rats. PRF could be considered clinically for patients with complicated pain and this study also demonstrated the role of BDNF in pain modulation. The optimal temperature for PRF was 42 °C.

In tumor cells, interleukin-6 (IL-6) signaling can lead to activation of the epidermal growth factor receptor (EGFR), which prolongs Stat3 activation. In the present experiments, we tested the hypothesis that IL-6 signaling activates EGFR signaling in peripheral and spinal nociception and examined whether EGFR localization and activation coincide with pain-related behaviors in arthritis. In vivo in anesthetized rats, spinal application of the EGFR receptor blocker gefitinib reduced the responses of spinal cord neurons to noxious joint stimulation, but only after spinal pretreatment with IL-6 and soluble IL-6 receptor. Using Western blots, we found that IL-6-induced Stat3 activation was reduced by gefitinib in microglial cells of the BV2 cell line, but not in cultured DRG neurons. Immunohistochemistry showed EGFR localization in most DRG neurons from normal rats, but significant downregulation in the acute and most painful arthritis phase. In the spinal cord of mice, EGFR was highly activated mainly in the chronic phase of inflammation, with localization in neurons. These data suggest that spinal IL-6 signaling may activate spinal EGFR signaling. Downregulation of EGFR in DRG neurons in acute arthritis may limit nociception, but pronounced delayed activation of EGFR in the spinal cord may be involved in chronic inflammatory pain.

Amyotrophic lateral sclerosis (ALS) is an extremely complex neurodegenerative disease involving different cell types, but motoneuronal loss represents its main pathological feature. Moreover, compensatory plastic changes taking place in parallel to neurodegeneration are likely to affect the timing of ALS onset and progression and, interestingly, they might represent a promising target for disease-modifying treatments. Therefore, a simplified animal model mimicking motoneuronal loss without the other pathological aspects of ALS has been established by means of intramuscular injection of cholera toxin-B saporin (CTB-Sap), which is a targeted neurotoxin able to kill motoneurons by retrograde suicide transport. Previous studies employing the mouse CTB-Sap model have proven that spontaneous motor recovery is possible after a subtotal removal of a spinal motoneuronal pool. Although these kinds of plastic changes are not enough to counteract the functional effects of the progressive motoneuron degeneration, it would nevertheless represent a promising target for treatments aiming to postpone ALS onset and/or delay disease progression. Herein, the mouse CTB-Sap model has been used to test the efficacy of mitochondrial division inhibitor 1 (Mdivi-1) as a tool to counteract the CTB-Sap toxicity and/or to promote neuroplasticity. The homeostasis of mitochondrial fission/fusion dynamics is indeed important for cell integrity, and it could be affected during neurodegeneration. Lesioned mice were treated with Mdivi-1 and then examined by a series of behavioral test and histological analyses. The results have shown that the drug may be capable of reducing functional deficits after the lesion and promoting synaptic plasticity and neuroprotection, thus representing a putative translational approach for motoneuron disorders.

BACKGROUND: Biomarkers predictive of disability outcomes in individual multiple sclerosis (MS) patients undergoing autologous haematopoietic stem cell transplantation (AHSCT) are currently lacking. As correlations between spinal cord atrophy and clinical disability in MS were previously described, in this study spinal cord size was investigated in MS patients treated with AHSCT, exploring whether baseline spinal cord volume may predict disability progression after AHSCT.
METHODS: relapsing-remitting (RR-) and secondary-progressive (SP-) MS patients treated with AHSCT (BEAM/ATG regimen) at a single academic centre in Florence, who performed at least two standardized brain magnetic resonance imaging (MRIs) scans (acquired between one-year pre-AHSCT to 5 years after AHSCT) were included. Cervical spinal cord atrophy was estimated as upper cervical spinal cord cross-sectional area (SCCSA). Brain volume loss (BVL) was analysed at the same timepoints.
RESULTS: Eleven (8 RR-; 3 SP-) MS patients were included. Over a median follow-up of 66 (range 37 - 100) months, no relapses nor brain MRI activity were observed; disability progressed in 2 cases (both SP-MS). Baseline SCCSA was associated with EDSS change between pre- and one-year post-AHSCT. Compared to patients who stabilized, patients who progressed after AHSCT tended to have lower SCCSA at C4 level at baseline and year 1 after AHSCT. Longitudinal changes in SCCSA or BVL did not correlate with EDSS change.
CONCLUSIONS: Baseline pre-AHSCT SCCSA, but not its longitudinal changes nor BVL, predicted EDSS change within the two years following AHSCT. SCCSA may represent a biomarker of treatment response and a promising screening tool for assessing patient eligibility for high-impact treatments such as AHSCT.

BACKGROUND: The neuropathic pain with complex networks of neuroinflammatory activation severely limits clinical therapeutic research. TNF receptor-associated factor 6 (TRAF6) is associated with multiple inflammatory diseases. However, there remains confusion about the effects and mechanisms of TRAF6 in neuropathic pain.
METHODS: A chronic constriction injury (CCI) model was developed to simulate neuralgia in vivo. We overexpressed or knocked down TRAF6 in CCI mice, respectively. Activation of microglia by TRAF6, the inflammatory response, and disease progression were inspected using WB, qRT-PCR, immunofluorescence, flow cytometry, and ELISA assays. Moreover, the mechanism of M1/M2 polarization activation of microglia by TRAF6 was elaborated in BV-2 cells.
RESULTS: TRAF6 was enhanced in the spinal neurons and microglia of the CCI mice model compared with the sham operation group.. Down-regulation of TRAF6 rescued the expression of Iba-1. In response to mechanical and thermal stimulation, PWT and PWL were improved after the knockdown of TRAF6. Decreased levels of pro-inflammatory factors were observed in TRAF6 knockdown groups. Meanwhile, increased microglial M1 markers induced by CCI were limited in mice with TRAF6 knockdown. In addition, TRAF6 overexpression has the precise opposite effect on CCI mice or microglia polarization. We also identifed that TRAF6 activated the c-JUN/NF-kB pathway signaling; the inhibitor of c-JUN/NF-kB could effectively alleviate the neuropathic pain induced by upregulated TRAF6 in the CCI mice model.
CONCLUSIONS: In summary, this study indicated that TRAF6 was concerned with neuropathic pain, and targeting the TRAF6/c-JUN/NF-kB pathway may be a prospective target for treating neuropathic pain.

Mercury chloride (ME) is a chemical pollutant commonly found in the environment, which can contribute to undesirable health consequence worldwide. The current study investigated the detrimental impact of ME on the cerebellum and spinal cord tissues in 6-8-week-old female rats. We also evaluated the neuroprotective efficacy of β-caryophyllene (BC) against spinal and cerebellar changes caused by ME. Thirty-five young Wistar albino rats were randomly chosen and assigned into five groups: control (CO), olive oil (OI), ME, BC, ME + BC. All samples were analysed by means of unbiased stereological, biochemical, immunohistochemical, and histopathological methods. Our biochemical findings showed that SOD level was significantly increased in the ME group compared to the CO group (p < 0.05). We additionally detected a statistically significant decrease in the number of cerebellar Purkinje cells and granular cells, as well as spinal motor neuron in the ME group compared to the CO group (p < 0.05). In the ME + BC group, the number of Purkinje cells, granular cells, and spinal motor neurons was significantly higher compared to the ME group (p < 0.05). Decreased SOD activity in the ME + BC group was also detected than the ME group (p < 0.05). Immunohistochemical (the tumour necrosis factor-alpha (TNF-α)) and histopathological examinations also exhibited crucial information in each of the group. Taken together, ME exposure was associated with neurotoxicity in the cerebellum and spinal cord tissues. BC treatment also mitigated ME-induced neurological alteration, which may imply its potential therapeutic benefits.

Traumatic spinal cord injuries (TSCIs) can lead to life-threatening consequences and neurological deficits. Sports activities significantly contribute to the incidence of these injuries. It is important to understand the epidemiology of sport-related spinal cord injuries (SCIs) in the Gulf region to improve patient care and increase awareness among this population. While studies from Saudi Arabia and Qatar have addressed SCIs related to both cycling and diving, we believe there is still significant scope for improvement in research on this topic. Special attention should be given to conducting retrospective studies across Gulf countries to establish a well-organized database.