Journal of Neurorestoratology最新文献

Objective

To study the effects and potential control mechanisms of the agrin signaling pathway on the repair of distal sciatic nerve damage.

Methods

50 Sprague-Dawleyrats were randomly allocated into the control group (SCI group, n = 25) and the treatment group (Treat group, n = 25). In both groups, the sciatic nerve damage model was created. Following surgery, the SCI group and the Treat group received intragastric administrations of normal saline and Jiawei Buyang Huanwu Decoction, respectively. The dose for both groups was 2mL/(kg·d) for 12 consecutive weeks. At 4, 8, and 12 weeks post-surgery, the wet-to-weight ratio of the gastrocnemius muscle in the two groups was assessed; and hematoxylin-eosin staining and Masson staining were used to detect pathological alterations in the sciatic nerve and collagen. The expression of agrin, Dag1, Dmd, and Lamb2 proteins in the agrin pathway, as well as ERK, MEK, and their corresponding phosphorylated proteins, p-ERK and p-MEK, were all detected by Western blot in the gastrocnemius muscle.

Results

The wet weight of the gastrocnemius muscle in the Treat group increased considerably (p < 0.05) after 4, 8, and 12 weeks following the operation compared to the SCI group, and it continued to rise over time. The expression level of Dag1, Dmd, and Lamb2 protein in agrin pathway, as well as p-ERK and p-MEK protein were all significantly lower than they were in the SCI group (p < 0.05). Additionally, Jiawei Buyang Huanwu Decoction greatly reduced the amount of nerve scars at the sciatic nerve injury and significantly healed sciatic neuropathy according to the results of pathological staining.

Conclusion

Jiawei Buyang Huanwu Decoction can inhibit the expression of agrin, Dag1, Dmd, and Lamb2, as well as p-ERK and p-MEK. It can effectively promote the distal repair of sciatic nerve injury probably through argin pathway.

Objective

To identify transcriptomic alterations and therapeutic drugs in different organs after spinal cord injury via comprehensive bioinformatics analyses.

Methods

RNA-sequencing data of the soleus muscle, bladder, liver, raphe, and sensorimotor cortex areas in various rat spinal cord injury models were obtained from the Gene Expression Omnibus database for bioinformatics analysis. Then, the common pathways and biological pathway changes in multiple organs were identified.

Results

By comparing the enrichment results of differentially expressed genes, inflammatory response and lipid metabolism were found to be significantly altered in multiple organs. The MAPK signaling pathway was a key pathway in the abovementioned biological processes. In addition, autonomous repair was observed in each organ. Finally, pharmacological analysis showed that coenzyme A might be an effective drug.

Conclusion

Coenzyme A is a candidate treatment drug for spinal cord injury. Hence, in addition to the current mechanisms targeted by anti-inflammatory approaches, lipid metabolism can also be a treatment target for spinal cord injury.

There was much progress in the field of Neurorestoratology in the year of 2022. It included highlighting advances in understanding the pathogenesis of neurological diseases, neurorestorative mechanisms, and clinical treatments as compiled in the 2022 yearbook of Neurorestoratology. There is still controversy about whether amyloid β-protein and tau protein deposition are the reasons for or the results of Alzheimer's disease (AD) pathology. The fabricated images in important key articles that speculated on the reasons for AD pathogenesis were found. Cholinergic deficiency and decrease or loss in strength of glutamatergic synapse, limited or failing bidirectional cholinergic upregulation in early cognitive impairment, or progressive posterior-to-anterior cortical cholinergic denervation could result in the appearance of AD. Exploration of neurorestorative mechanisms were found in more detail ways in neuromodulation, immunomodulation, neurogenesis, neural network or circuitry reconstruction, neuroprotection, nervous structural repair, and neuroplasticity. Several kinds of cell therapies for neurological diseases showed neurorestorative effects in open-label and/or non-randomized clinical studies or trials. However, mesenchymal stromal cells and mononuclear cells did not demonstrate neurorestorative effects or improve the quality of life for patients with neurodegenerative diseases or neurotrauma including stroke, spinal cord injury (SCI), and amyotrophic lateral sclerosis in randomized, double-blind, placebo-controlled clinical trials (RDPCTs). Clinical treatments through neurostimulation/neuromodulation and the brain–computer/machine interface yielded positive results in AD, Parkinson's disease, stroke, SCI, cerebral palsy, and other diseases in RDPCTs. Neurorestorative surgery, pharmaceutical neurorestorative therapy and other interventions have demonstrated neurorestorative effects for various considered incurable neurological diseases in RDPCTs. Thus, this year, additional guidelines, assessment scales, and standards were set up or revised. These included guidelines of clinical neurorestorative treatments for brain trauma (2022 China version), clinical cell therapy guidelines for neurorestoration (IANR/CANR 2022), SCI or dysfunction quality of life rating scale (SCIDQLRS) (IANR 2022 version). Neurorestorative effects of varying therapeutic strategies with higher standards of evidence-based medicine are now benefiting patients with currently incurable neurological diseases. Hopefully some of them may become routine therapeutic interventions for patients with these diseases in the near future.

Recent advances in upstream medical therapies for neuromuscular disorders suggest that the best outcomes result from their administration in the pre-symptomatic, and perhaps, neonatal period. Currently available therapies, and many other extremely expensive therapies in the pipeline soon to be considered by the Food and Drug Administration, and suggest the importance of avoiding potential life-threatening disease complications for patients to continue to benefit from these. There is evidence that this is almost always possible with the use of respiratory muscle aids to avoid pneumonias and respiratory failure, but these are currently little understood and rarely offered by the medical community. However, restoring neuromuscular function necessitates keeping the patient alive and well.

Protein polymers derived from mesenchymal stem cells, especially human umbilical cord mesenchymal stem cells, showed promising potentials in treating ischemic stroke, thanks to the advantages of selective assembly, targeted delivery, efficient repair of damaged tissues, high safety, highly stable chemical properties, and being easy for storage. Herein, we introduced a clinical trial based on protein polymers derived from human umbilical cord mesenchymal stem cells. The main purpose of this clinical study is to preliminarily verify the safety and efficacy of intrathecal administration and application of protein polymers in clinical treatment of ischemic stroke cases. The summary of the program, the research plan, test protein polymer intrathecal injection method, experimental protein polymer management, patient evaluation index, data management and statistical analysis, technical features, trial schedule etc. are detailed described in the article. This clinical study provides information for other clinical trials based on protein polymers and medicines used to treat apoplexy.

Objective

The goal of this research was to evaluate the clinical characteristics of patients with primary progressive freezing of gait (PPFOG).

Patients and methods

This retrospective study enrolled 8 PPFOG patients and 10 age-matched Parkinson's disease with freezing of gait (PDFOG) patients. All patients underwent structured forms to document clinical manifestations and neuropsychological evaluations.

Result

PPFOG patients demonstrated later onset age than PDFOG patients (70.00 ± 9.97 years versus 53.30 ± 5.40 years, respectively; P < 0.05). Besides FOG (100%), the most prevalent concomitant symptoms of PPFOG patients were falling (n = 6, 75%), and fatigue (n = 5, 62.5%). More PPFOG patients had cerebrovascular risk factors and mild brain magnetic resonance imaging (MRI) abnormalities, which were constant with the manifestations of “cerebral small vessel disease” (P = 0.0001).

Conclusion

According to this study, the majority of PPFOG patients were linked with cerebrovascular disease risk factors and mild brain MRI abnormalities. More research on larger populations is needed to better understand the potential mechanisms underlying the link between PPFOG and cerebral small vessel disease.

CX3C chemokine ligand 1 (CX3CL1), a unique member of the CX3C family, is most widely expressed in endothelial cells and neurons. Its specific receptor is CX3CR1, which is mainly expressed in central nervous system (CNS) microglia. CX3CL1 has effects on the brain and neurological system. CX3CL1 and its specific receptor CX3CR1 can inhibit calcium influx in neurons, promote the activation of protein kinases and the activation of nuclear transcription factor кB, etc., thereby reducing the release of inflammatory factors and achieving small stable glue in the state of plasmocytes and inhibiting the inflammatory response in CNS. This phenomenon limits neuronal death to a certain extent and has a particular neuroprotective effect. Currently, the CX3CL1/CX3CR1 signal axis impact is of particular interest in a variety of CNS disorders, such as Alzheimer's disease, stroke, cerebral small vessel disease, Parkinson's disease, epilepsy, and other diseases. A wealth of studies has reported CX3CL1/CX3CR1 signal axis as a functional regulator of microglia, thereby affecting the occurrence and development of CNS diseases. The current article briefly enlightens the role of the CX3CL1/CX3CR1 signal axis and microglia and its effect on CNS diseases.

Background

Clinicians are often faced with apparently tracheostomy mechanical ventilation dependent (TMV), patients who are ventilator unweanable due to encephalopathic/upper motor neuron conditions, that hamper return to the community.

Objectives

A protocol is suggested to wean these patients from mechanical ventilation and criteria offered for possible decannulation.

Methods

After excluding patients with severe muscle weakness due to neuromuscular diseases and high level spinal cord disorders, consecutive, apparently unweanable and unresponsive encephalopathic patients were to be weaned by a protocol that first normalized CO₂ levels at full ventilatory support settings. Then, supplemental oxygen was discontinued so that ambient air baseline oxyhemoglobin saturation (O₂ Sat) could be determined and subsequently be normalized by using mechanical insufflation–exsufflation (MIE), at 60–70 cmH₂O pressures, via the tubes every 2 hours, with the tube cuffs inflated. Once ambient air O₂ Sat levels remained normal, ambient air spontaneous, unassisted autonomous breathing “sprints” were initiated and continued until O₂ Sat decreased below 95% with respiratory distress. Patients spontaneously moving over 300 mL of air into their lungs without pressure support had very good prognoses for rapid ventilator weaning. Patients were not returned to TMV irrespective of tachypnea. After the “sprint”, they were rested by using 1–3 hours of full ventilatory support before the next sprint. Sprints lengthened until being fully weaned. After weaning, potential decannulation was evaluated using MIE expiratory flows (MIE-EF) and O₂ Sat.

Results

O₂ Sat normalized from the initial use of MIE via the tube for 7 of 13 patients then 4 weaned from the initial ambient air sprint. Weaning occurred in 4 days or less for 11 of 13. Despite continuous TMV dependence for 31 days to 15 months before the intervention, 7 weaned patients were successfully decannulated, 6 of the 7 with MIE-EF ≥ 190 L/m. All but 2 remained unresponsive, but 6 were discharged home to their families once decannulated.

Conclusion

Once primary ventilatory pump failure is excluded and lung disease improved to the extent that the ambient air O₂ Sat can be normalized by using MIE via invasive airway tubes to clear airway secretions, encephalopathic patients can have sufficient muscle strength to wean from ventilatory support and possibly be decannulated if mechanically augmented cough flows exceed 190 L/m.

The growing body of evidence associates infections during pregnancy and other inflammatory insults with developing neurodevelopmental and neurodevelopmental disorders in children, especially autism spectrum disorder. We review the specific roles that maternal immune activation (MIA) plays in the pathogenesis of autism, the critical cytokines involved, epigenetic factors, maternal antibodies and gender bias, and how MIA affects fetal neurodevelopment in the immune and neurological pathways. A comprehensive understanding of the profound impact of MIA on fetal neurodevelopment is vital for developing diagnostic criteria and medical measures for high-risk maternity and the development of treatments for multiple offspring neurodevelopmental disorders caused by maternal inflammation.