-
Journal of Nanobiotechnology Jun 2024Molybdenum disulfide (MoS) has excellent physical and chemical properties. Further, chiral MoS (CMS) exhibits excellent chiroptical and enantioselective effects, and the...
BACKGROUND
Molybdenum disulfide (MoS) has excellent physical and chemical properties. Further, chiral MoS (CMS) exhibits excellent chiroptical and enantioselective effects, and the enantioselective properties of CMS have been studied for the treatment of neurodegenerative diseases. Intriguingly, left- and right-handed materials have different effects on promoting the differentiation of neural stem cells into neurons. However, the effect of the enantioselectivity of chiral materials on peripheral nerve regeneration remains unclear.
METHODS
In this study, CMS@bacterial cellulose (BC) scaffolds were fabricated using a hydrothermal approach. The CMS@BC films synthesized with L-2-amino-3-phenyl-1-propanol was defined as L-CMS. The CMS@BC films synthesized with D-2-amino-3-phenyl-1-propanol was defined as D-CMS. The biocompatibility of CMS@BC scaffolds and their effect on Schwann cells (SCs) were validated by cellular experiments. In addition, these scaffolds were implanted in rat sciatic nerve defect sites for three months.
RESULTS
These chiral scaffolds displayed high hydrophilicity, good mechanical properties, and low cytotoxicity. Further, we found that the L-CMS scaffolds were superior to the D-CMS scaffolds in promoting SCs proliferation. After three months, the scaffolds showed good biocompatibility in vivo, and the nerve conducting velocities of the L-CMS and D-CMS scaffolds were 51.2 m/s and 26.8 m/s, respectively. The L-CMS scaffolds showed a better regenerative effect than the D-CMS scaffolds. Similarly, the sciatic nerve function index and effects on the motor and electrophysiological functions were higher for the L-CMS scaffolds than the D-CMS scaffolds. Finally, the axon diameter and myelin sheath thickness of the regenerated nerves were improved in the L-CMS group.
CONCLUSION
We found that the CMS@BC can promote peripheral nerve regeneration, and in general, the L-CMS group exhibited superior repair performance. Overall, the findings of this study reveal that CMS@BC can be used as a chiral nanomaterial nerve scaffold for peripheral nerve repair.
Topics: Nerve Regeneration; Animals; Rats; Tissue Scaffolds; Disulfides; Schwann Cells; Molybdenum; Cellulose; Rats, Sprague-Dawley; Biocompatible Materials; Sciatic Nerve; Cell Proliferation; Tissue Engineering; Male; Peripheral Nerve Injuries; Stereoisomerism
PubMed: 38886712
DOI: 10.1186/s12951-024-02493-6 -
Neuroscience and Biobehavioral Reviews Jun 2024Multiple sclerosis (MS) is a severe neurological disorder that involves inflammation in the brain, spinal cord and optic nerve with key disabling neuropathological... (Review)
Review
Multiple sclerosis (MS) is a severe neurological disorder that involves inflammation in the brain, spinal cord and optic nerve with key disabling neuropathological outcomes being axonal damage and demyelination. When degeneration of the axo-glial union occurs, a consequence of inflammatory damage to central nervous system (CNS) myelin, dystrophy and death can lead to large membranous structures from dead oligodendrocytes and degenerative myelin deposited in the extracellular milieu. For the first time, this review covers mitochondrial mechanisms that maybe operative during MS-related neurodegenerative changes directly activated during accumulating extracellular deposits of myelin associated inhibitory factors (MAIFs), that include the potent inhibitor of neurite outgrowth, Nogo-A. Axonal damage may occur when Nogo-A binds to and signals through its cognate receptor, NgR1, multimeric complex, to initially stall axonal transport and limit the delivery of important growth-dependent cargo and subcellular organelles such as mitochondria for metabolic efficiency at sites of axo-glial disintegration as a consequence of inflammation. Metabolic efficiency in axons fails during active demyelination and progressive neurodegeneration, preceded by stalled transport of functional mitochondria to fuel axo-glial integrity.
PubMed: 38885889
DOI: 10.1016/j.neubiorev.2024.105767 -
Communications Medicine Jun 2024Spinal muscular atrophy (SMA) is a fatal autosomal recessive disorder for which several treatment options, including a gene therapy, have become available. SMA incidence...
BACKGROUND
Spinal muscular atrophy (SMA) is a fatal autosomal recessive disorder for which several treatment options, including a gene therapy, have become available. SMA incidence has not been well-characterized in most Arab countries where rates of consanguinity are high. Understanding SMA disease epidemiology has important implications for screening, prevention, and treatment in those populations.
METHODS
We perform SMA diagnostic testing in a clinical multi-national patient cohort (N = 171) referred for hypotonia and/or muscle weakness. In addition, we carry out genetic newborn screening for SMA on 1502 healthy Emirati newborns to estimate the carrier frequency and incidence of the disease in the United Arab Emirates.
RESULTS
Patients referred for SMA genetic testing are mostly Arabs (82%) representing 18 countries. The overall diagnostic yield is 33.9%, which is higher (>50%) for certain nationalities. Most patients (71%) has two SMN2 copies and earlier disease onset. For the first time, we estimate SMA carrier frequency (1.3%) and incidence of the disease (1 in 7122 live births) in the United Arab Emirates. Using birth and marriage rates in two Arab populations (United Arab Emirates and Saudi Arabia), as well as disease incidence in both countries, we show that, besides preventing new cases, premarital genetic screening could potentially result in around $8 to $324 million annual cost savings, respectively, relative to postnatal treatment.
CONCLUSIONS
The SMA carrier frequency and incidence we document suggests high potential benefit for universal implementation of premarital genomic screening for a wide range of recessive disorders in Arab populations.
PubMed: 38879606
DOI: 10.1038/s43856-024-00548-1 -
Arthritis Research & Therapy Jun 2024Janus kinase (JAK) inhibitors, such as baricitinib, are widely used to treat rheumatoid arthritis (RA). Clinical studies show that baricitinib is more effective at...
Baricitinib ameliorates inflammatory and neuropathic pain in collagen antibody-induced arthritis mice by modulating the IL-6/JAK/STAT3 pathway and CSF-1 expression in dorsal root ganglion neurons.
BACKGROUND
Janus kinase (JAK) inhibitors, such as baricitinib, are widely used to treat rheumatoid arthritis (RA). Clinical studies show that baricitinib is more effective at reducing pain than other similar drugs. Here, we aimed to elucidate the molecular mechanisms underlying the pain relief conferred by baricitinib, using a mouse model of arthritis.
METHODS
We treated collagen antibody-induced arthritis (CAIA) model mice with baricitinib, celecoxib, or vehicle, and evaluated the severity of arthritis, histological findings of the spinal cord, and pain-related behaviours. We also conducted RNA sequencing (RNA-seq) to identify alterations in gene expression in the dorsal root ganglion (DRG) following baricitinib treatment. Finally, we conducted in vitro experiments to investigate the direct effects of baricitinib on neuronal cells.
RESULTS
Both baricitinib and celecoxib significantly decreased CAIA and improved arthritis-dependent grip-strength deficit, while only baricitinib notably suppressed residual tactile allodynia as determined by the von Frey test. CAIA induction of inflammatory cytokines in ankle synovium, including interleukin (IL)-1β and IL-6, was suppressed by treatment with either baricitinib or celecoxib. In contrast, RNA-seq analysis of the DRG revealed that baricitinib, but not celecoxib, restored gene expression alterations induced by CAIA to the control condition. Among many pathways changed by CAIA and baricitinib treatment, the interferon-alpha/gamma, JAK-signal transducer and activator of transcription 3 (STAT3), and nuclear factor kappa B (NF-κB) pathways were considerably decreased in the baricitinib group compared with the celecoxib group. Notably, only baricitinib decreased the expression of colony-stimulating factor 1 (CSF-1), a potent cytokine that causes neuropathic pain through activation of the microglia-astrocyte axis in the spinal cord. Accordingly, baricitinib prevented increases in microglia and astrocytes caused by CAIA. Baricitinib also suppressed JAK/STAT3 pathway activity and Csf1 expression in cultured neuronal cells.
CONCLUSIONS
Our findings demonstrate the effects baricitinib has on the DRG in relation to ameliorating both inflammatory and neuropathic pain.
Topics: Animals; Azetidines; Sulfonamides; Pyrazoles; STAT3 Transcription Factor; Purines; Arthritis, Experimental; Ganglia, Spinal; Neuralgia; Janus Kinases; Signal Transduction; Mice; Interleukin-6; Male; Neurons; Mice, Inbred DBA; Inflammation; Janus Kinase Inhibitors
PubMed: 38879555
DOI: 10.1186/s13075-024-03354-1 -
Journal of Neuroimmune Pharmacology :... Jun 2024Chronic neuropathic pain precipitates a complex range of affective and behavioural disturbances that differ markedly between individuals. While the reasons for...
Chronic neuropathic pain precipitates a complex range of affective and behavioural disturbances that differ markedly between individuals. While the reasons for differences in pain-related disability are not well understood, supraspinal neuroimmune interactions are implicated. Minocycline has antidepressant effects in humans and attenuates affective disturbances in rodent models of pain, and acts by reducing neuroinflammation in both the spinal cord and brain. Previous studies, however, tend not to investigate how minocycline modulates individual affective responses to nerve injury, or rely on non-naturalistic behavioural paradigms that fail to capture the complexity of rodent behaviour. We investigated the development and resolution of pain-related affective disturbances in nerve-injured male rats by measuring multiple spontaneous ethological endpoints on a longitudinal naturalistic foraging paradigm, and the effect of chronic oral minocycline administration on these changes. Disrupted foraging behaviours appeared in 22% of nerve-injured rats - termed 'affected' rats - and were present at day 14 but partially resolved by day 21 post-injury. Minocycline completely prevented the emergence of an affected subgroup while only partly attenuating mechanical allodynia, dissociating the relationship between pain and affect. This was associated with a lasting downregulation of ΔFosB expression in ventral hippocampal neurons at day 21 post-injury. Markers of microglia-mediated neuroinflammation were not present by day 21, however proinflammatory microglial polarisation was apparent in the medial prefrontal cortex of affected rats and not in CCI minocycline rats. Individual differences in affective disturbances following nerve injury are therefore temporally related to altered microglial morphology and hippocampal neuronal activation, and are abrogated by minocycline.
Topics: Animals; Minocycline; Male; Rats; Neuroinflammatory Diseases; Rats, Sprague-Dawley; Neuralgia; Hyperalgesia; Individuality; Mood Disorders; Peripheral Nerve Injuries
PubMed: 38878098
DOI: 10.1007/s11481-024-10132-y -
BMC Musculoskeletal Disorders Jun 2024Complete fractures and dislocations of the lower cervical spine are usually associated with severe spinal cord injury. However, a very small number of patients do not...
BACKGROUND
Complete fractures and dislocations of the lower cervical spine are usually associated with severe spinal cord injury. However, a very small number of patients do not have severe spinal cord injury symptoms, patients with normal muscle strength or only partial nerve root symptoms, known as "lucky fracture dislocation". The diagnosis and treatment of such patients is very difficult. Recently, we successfully treated one such patient.
CASE PRESENTATION
A 73-year-old male patient had multiple neck and body aches after trauma, but there was sensory movement in his limbs. However, preoperative cervical radiographs showed no significant abnormalities, and computed tomography (CT) and magnetic resonance imaging (MRI) confirmed complete fracture and dislocation of C7. Before operation, the halo frame was fixed traction, but the reduction was not successful. Finally, the fracture reduction and internal fixation were successfully performed by surgery. The postoperative pain of the patient was significantly relieved, and the sensory movement of the limbs was the same as before. Two years after surgery, the patient's left little finger and ulnar forearm shallow sensation recovered, and the right flexion muscle strength basically returned to normal.
CONCLUSION
This case suggests that when patients with trauma are encountered in the clinic, they should be carefully examined, and the presence of cervical fracture and dislocation should not be ignored because of the absence of neurological symptoms or mild symptoms. In addition, positioning during handling and surgery should be particularly avoided to increase the risk of paralysis.
Topics: Humans; Male; Aged; Cervical Vertebrae; Spinal Fractures; Fracture Fixation, Internal; Tomography, X-Ray Computed; Fracture Dislocation; Treatment Outcome; Joint Dislocations; Magnetic Resonance Imaging
PubMed: 38877489
DOI: 10.1186/s12891-024-07586-9 -
JBJS Reviews Jun 2024» Tumors of the brachial plexus are uncommon and can present as a mass, with or without neurological symptoms. At times, asymptomatic tumors are also picked up... (Review)
Review
» Tumors of the brachial plexus are uncommon and can present as a mass, with or without neurological symptoms. At times, asymptomatic tumors are also picked up incidentally when imaging is performed for other reasons.» Magnetic resonance imaging is the main imaging modality used to evaluate tumors of the brachial plexus. Other imaging modalities can be used as required.» Benign tumors that are asymptomatic should be observed. Excision can be considered for those that are found to be growing over time.» Biopsies of tumors of the brachial plexus are associated with the risk of nerve injury. Despite this, they should be performed for tumors that are suspected to be malignant before starting definitive treatment.» For malignant tumors, treatment decisions should be discussed at multidisciplinary tumor boards, and include both the oncology and peripheral nerve surgical team, musculoskeletal radiology, neuroradiology, and general radiology.
Topics: Humans; Brachial Plexus; Peripheral Nervous System Neoplasms; Magnetic Resonance Imaging
PubMed: 38875357
DOI: 10.2106/JBJS.RVW.24.00019 -
Journal of the Korean Society of... May 2024Recent studies have demonstrated the usefulness of diffusion-weighted MR neurography (DW MRN) for assessing nerve roots. This study aimed to evaluate the utility of DW...
PURPOSE
Recent studies have demonstrated the usefulness of diffusion-weighted MR neurography (DW MRN) for assessing nerve roots. This study aimed to evaluate the utility of DW MRN with a unidirectional motion-probing gradient (MPG) for the lumbar nerve roots at 1.5T MR.
MATERIALS AND METHODS
Sixty-four lumbar spine MRI scans with DW MRN using anteroposterior unidirectional MPG were retrospectively analyzed. Any changes in the 512 lumbar spinal nerve roots from L3 to S1 were evaluated using T2-weighted imaging (T2WI), contrast-enhanced T1-weighted imaging (CE T1WI), and DW MRN, with agreement and correlation analysis.
RESULTS
T2WI revealed compression of 78 nerve roots, and CE T1WI revealed 52 instances of nerve root enhancement. Sixty-seven nerve roots showed swelling and hyperintensity on DW MRN. A total of 42 nerve roots showed changes in the CE T1WI and DW MRN sequences. Moderate to substantial agreement and moderate positive correlation were observed between DW MRN and CE T1WI, as well as DW MRN and T2WI (κ = 0.59-0.65, ρ = 0.600-0.653).
CONCLUSION
DW MRN with unidirectional anteroposterior MPG can help evaluate neuritis-related changes in spinal nerve roots and could serve as a sequence capable of complementing or substituting gadolinium CE imaging.
PubMed: 38873379
DOI: 10.3348/jksr.2023.0052 -
Frontiers in Neurology 2024To systematically review vagus nerve stimulation (VNS) studies to present data on the safety and efficacy on motor recovery following stroke, traumatic brain injury...
OBJECTIVE
To systematically review vagus nerve stimulation (VNS) studies to present data on the safety and efficacy on motor recovery following stroke, traumatic brain injury (TBI), and spinal cord injury (SCI).
METHODS
Data sources: PubMed, EMBASE, SCOPUS, and Cochrane.
STUDY SELECTION
Clinical trials of VNS in animal models and humans with TBI and SCI were included to evaluate the effects of pairing VNS with rehabilitation therapy on motor recovery.
DATA EXTRACTION
Two reviewers independently assessed articles according to the evaluation criteria and extracted relevant data electronically.
DATA SYNTHESIS
Twenty-nine studies were included; 11 were animal models of stroke, TBI, and SCI, and eight involved humans with stroke. While there was heterogeneity in methods of delivering VNS with respect to rehabilitation therapy in animal studies and human non-invasive studies, a similar methodology was used in all human-invasive VNS studies. In animal studies, pairing VNS with rehabilitation therapy consistently improved motor outcomes compared to controls. Except for one study, all human invasive and non-invasive studies with controls demonstrated a trend toward improvement in motor outcomes compared to sham controls post-intervention. However, compared to non-invasive, invasive VNS, studies reported severe adverse events such as vocal cord palsy, dysphagia, surgical site infection, and hoarseness of voice, which were found to be related to surgery.
CONCLUSION
Our review suggests that VNS (non-invasive or invasive) paired with rehabilitation can improve motor outcomes after stroke in humans. Hence, VNS human studies are needed in these populations (referring to SCI and TBI?) or just SCI. There are risks related to device implantation to deliver invasive VNS compared to non-invasive VNS. Future human comparison studies are required to study and quantify the efficacy vs. risks of paired VNS delivered via different methods with rehabilitation, which would allow patients to make an informed decision.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=330653.
PubMed: 38872818
DOI: 10.3389/fneur.2024.1390217 -
BMC Musculoskeletal Disorders Jun 2024Double crush syndrome refers to a nerve in the proximal region being compressed, affecting its proximal segment. Instances of this syndrome involving ulnar and cubital... (Review)
Review
BACKGROUND
Double crush syndrome refers to a nerve in the proximal region being compressed, affecting its proximal segment. Instances of this syndrome involving ulnar and cubital canals during ulnar neuropathy are rare. Diagnosis solely through clinical examination is challenging. Although electromyography (EMG) and nerve conduction studies (NCS) can confirm neuropathy, they do not incorporate inching tests at the wrist, hindering diagnosis confirmation. We recently encountered eight cases of suspected double compression of ulnar nerve, reporting these cases along with a literature review.
METHODS
The study included 5 males and 2 females, averaging 45.6 years old. Among them, 4 had trauma history, and preoperative McGowan stages varied. Ulnar neuropathy was confirmed in 7 cases at both cubital and ulnar canal locations. Surgery was performed for 4 cases, while conservative treatment continued for 3 cases.
RESULTS
In 4 cases with wrist involvement, 2 showed ulnar nerve compression by a fibrous band, and 1 had nodular hyperplasia. Another case displayed ulnar nerve swelling with muscle covering. Among the 4 surgery cases, 2 improved from preoperative McGowan stage IIB to postoperative stage 0, with significant improvement in subjective satisfaction. The remaining 2 cases improved from stage IIB to IIA, respectively, with moderate improvement in subjective satisfaction. In the 3 cases receiving conservative treatment, satisfaction was significant in 1 case and moderate in 2 cases. Overall, there was improvement in hand function across all 7 cases.
CONCLUSION
Typical outpatient examinations make it difficult to clearly differentiate the two sites, and EMG tests may not confirm diagnosis. Therefore, if a surgeon lacks suspicion of this condition, diagnosis becomes even more challenging. In cases with less than expected postoperative improvement in clinical symptoms of cubital tunnel syndrome, consideration of double crush syndrome is warranted. Additional tests and detailed EMG tests, including inching tests at the wrist, may be necessary. We aim to raise awareness double crush syndrome with ulnar nerve, reporting a total of 7 cases to support this concept.
Topics: Humans; Male; Female; Middle Aged; Adult; Ulnar Nerve Compression Syndromes; Ulnar Nerve; Electromyography; Crush Syndrome; Wrist; Neural Conduction; Elbow; Treatment Outcome; Aged
PubMed: 38872094
DOI: 10.1186/s12891-024-07574-z