Chemokine platelet factor 4 accelerates peripheral nerve regeneration by regulating Schwann cell activation and axon elongation

Schwann cells in peripheral nerves react to traumatic nerve injury by attempting to grow and regenerate.Howeve r,it is unclear what factors play a role in this process.In this study,we searched a GEO database and found that expression of platelet factor 4 was markedly up-regulated after sciatic nerve injury.Platelet factor is an important molecule in cell apoptosis,diffe rentiation,survival,and proliferation.Further,polymerase chain reaction and immunohistochemical staining confirmed the change in platelet factor 4 in the sciatic nerve at different time points after injury.Enzyme-linked immunosorbent assay confirmed that platelet factor 4 was secreted by Schwann cells.We also found that silencing platelet factor 4 decreased the proliferation and migration of primary cultured Schwann cells,while exogenously applied platelet factor 4 stimulated Schwann cell prolife ration and migration and neuronal axon growth.Furthermore,knocking out platelet factor 4 inhibited the prolife ration of Schwann cells in injured rat sciatic nerve.These findings suggest that Schwann cell-secreted platelet factor 4 may facilitate peripheral nerve repair and regeneration by regulating Schwann cell activation and axon growth.Thus,platelet factor 4 may be a potential therapeutic target for traumatic peripheral nerve injury.

Current Status of Neuromodulatory Therapies for Disorders of Consciousness

Treatment for disorders of consciousness （DOCs） is still a Gordian knot. Evidence-based guidelines on the treatment of DOC patients are not currently available, while neuromodulation techniques are seen as a potential treatment. Multiple neuromodulation therapies have been applied. This article reviews the most relevant studies in the literature in order to describe a clear picture of the current state of neuromodulation therapies that could be used to treat DOC patients. Both invasive and noninvasive brain stimulation is discussed. Significant behavioral improvements in prolonged DOCs under neuromodulation therapies are rare. The efficacy of various such therapies remains a matter of debate. Further clinical investigations of existing techniques in larger samples properly controlling for spontaneous recovery are needed, and new approaches are awaited.

Spinal Cord Stimulation Frequency Influences the Hemodynamic Response in Patients with Disorders of Consciousness

Spinal cord stimulation （SCS） is a promising technique for treating disorders of consciousness （DOCs）. However, differences in the spatio-temporal responsiveness of the brain under varied SCS parameters remain unclear. In this pilot study, functional near-infrared spectroscopy was used to measure the hemodynamic responses of 10 DOC patients to different SCS frequencies （5 Hz, 10 Hz, 50 Hz, 70 Hz, and 100 Hz）. In the prefrontal cortex, a key area in consciousness circuits, we found significantly increased hemodynamic responses at 70 Hz and 100 Hz, and significantly different hemodynamic responses between 50 Hz and 70 Hz/100 Hz. In addition, the functional connectivity between prefrontal and occipital areas was significantly improved with SCS at 70 Hz. These results demonstrated that SCS modulates the hemodynamic responses and long-range connectivity in a frequency-specific manner （with 70 Hz apparently better）, perhaps by improving the cerebral blood volume and information transmission through the reticular formation-thalamus-cortex pathway.

七氟醚与丙泊酚对慢性意识障碍患者全身麻醉期间脑电的影响

目的:探讨七氟醚吸入麻醉与丙泊酚静脉麻醉对慢性意识障碍(pDoC)患者围术期脑电的影响。方法:前瞻性纳入解放军总医院第七医学中心神经外科和首都医科大学附属天坛医院神经外科自2022年1月至8月拟行短程脊髓电刺激术(st-SCS)的20例pDoC患者,按照随机数字表法分为七氟醚组(10例)和丙泊酚组(10例)。采用19通道脑电设备记录2组患者麻醉前、麻醉中、麻醉后3个时间段全脑的脑电活动变化。结果:2组患者麻醉中的脑电功率谱均以δ功率增加,θ、β、γ功率减少为特征。麻醉后,七氟醚组较丙泊酚组有更多的快波活动(θ+α+β)和更少的慢波活动(δ)。脑电指标区分清醒和麻醉状态的ROC曲线显示,以额叶区域的置换熵(PE)和置换Lempel-Ziv复杂度(PLZC)指标区分度最好,丙泊酚额叶PE(AUC:0.865)大于七氟醚额叶PE(AUC:0.815),丙泊酚额叶PLCZ(AUC:0.865)大于七氟醚(AUC:0.810)。结论:七氟醚与丙泊酚对pDoC患者麻醉状态的脑电活动影响是类似的,但七氟醚组比丙泊酚组具有更好的苏醒后表现。脑电监测对评估全麻期间意识状态有重要意义,快慢波功率比值、PE、PLZC等作为表征麻醉深度的脑电指标在pDoC患者中表现出较强的适用性,额叶区域的PE和PLZC区分清醒和麻醉的能力最强。

Brain-Computer Interfaces in Disorders of Consciousness

The development of brain-computer interfaces(BCIs)has established a new communication channel between the brain and external devices for information transmission that requires no muscular signals[1].BCIs have been preliminarily studied to improve motor functions in patients with severe motor disabilities,especially lock-in syndrome.At present,the application of BCIs has been extensively validated.

Long-term functional outcomes improved with deep brain stimulation in patients with disorders of consciousness

Background Deep brain stimulation(DBS)has been preliminarily applied to treat patients with disorders of consciousness(DoCs).The study aimed to determine whether DBS was effective for treating patients with DoC and identify factors related to patients’outcomes.Methods Data from 365 patients with DoCs who were consecutively admitted from 15 July 2011 to 31 December 2021 were retrospectively analysed.Multivariate regression and subgroup analysis were performed to adjust for potential confounders.The primary outcome was improvement in consciousness at 1 year.Results An overall improvement in consciousness at 1 year was achieved in 32.4%(12/37)of the DBS group compared with 4.3%(14/328)of the conservative group.After full adjustment,DBS significantly improved consciousness at 1 year(adjusted OR 11.90,95%CI 3.65-38.46,p<0.001).There was a significant treatment×follow up interaction(H=14.99,p<0.001).DBS had significantly better effects in patients with minimally conscious state(MCS)compared with patients with vegetative state/unresponsive wakefulness syndrome(p for interaction<0.001).A nomogram based on age,state of consciousness,pathogeny and duration of DoCs indicated excellent predictive performance(c-index=0.882).Conclusions DBS was associated with better outcomes in patients with DoC,and the effect was likely to be significantly greater in patients with MCS.DBS should be cautiously evaluated by nomogram preoperatively,and randomised controlled trials are still needed.

Spatial Properties of Mismatch Negativity in Patients with Disorders of Consciousness

In recent decades, event-related potentials have been used for the clinical electrophysiological assessment of patients with disorders of consciousness （DOCs）. In this paper, an oddball paradigm with two types of frequencydeviant stimulus （standard stimuli were pure tones of 1000 Hz; small deviant stimuli were pure tones of 1050 Hz; large deviant stimuli were pure tones of 1200 Hz） was applied to elicit mismatch negativity （MMN） in 30 patients with DOCs diagnosed using the JFK Coma Recovery Scale- Revised （CRS-R）. The results showed that the peak amplitudes of MMN elicited by both large and small deviant stimuli were significantly different from baseline. In terms of the spatial properties of MMN, a significant interaction effect between conditions （small and large deviant stimuli） and electrode nodes was centered at the frontocentral area. Furthermore, correlation coefficients were calculated between MMN amplitudes and CRS-R scores for each electrode among all participants to generate topographic maps. Meanwhile, a significant negative correlation between the MMN amplitudes elicited by large deviant stimuli and the CRS-R scores was also found at the frontocentral area. In consequence, our results combine the above spatial properties of MMN in patients with DOCs, and provide a more precise location （frontocentral area） at which to evaluate the correlation between clinical electrophysiological assessment and the level of consciousness.

Diagnostic evaluation of patients with disorders of consciousness with diffusion tensor imaging

Background:With the development of emergency and intensive medical technologies,the survival rate of traumatic brain injury has greatly increased.More and more patients have been converted from severe coma to alleviated state of consciousness,which can be subsequently classified within the framework of disorders of consciousness (DOC).We investigated the clinical application and characteristics of imaging indicators of diffusion tensor imaging (DTI) for the DOC patients.Methods:DTI was performed on a total of 75 cases with a clinical diagnosis of DOC from January 2014 to December 2015 in Beijing Tiantan Hospital and PLA Army General Hospital (including 66 cases of unresponsive wakefulness state (UWS) patients and 9 cases of minimally conscious state (MCS) patients).The data for the imaging indicators,such as fractional anisotropy (FA) and mean diffusivity (MD),were separately collected from three relevant regions of interest (ROIs):brainstem,thalamus,and subcortex.The indicators of two groups with different conscious states were statistically analyzed,and correlation analyses were conducted for the mean values of FA and MD in the ROIs evaluated through clinical Coma Recovery Scale-Revised (CRS-R) scores.Results:The FA value of the UWS group was evidentially lower than that of the MCS group (P ＜ 0.05),while the MD value of the UWS group was higher than that of the MCS group (P ＜ 0.05);the difference was statistically significant.The FA and MD values in the ROIs (locations:brainstem,thalamus,and subcortex) correlated with CRS-R scores,particularly in the thalamus.Conclusion:DTI has a certain clinical reference value for DOC imaging grading.The more severe the DOC,the higher the MD value and the lower the FA value.

Combination of Biomedical Techniques and Paradigms to Improve Prognostications for Disorders of Consciousness

For a long time,patients with disorders of consciousness(DoCs)have been considered to have a universally poor prognosis.However,along with the development of rehabilitation and nursing technology,the findings from recent clinical studies herald a philosophical shift:some DoC patients may have a better outcome than originally thought.A recent review suggests that>40%of DoC patients have the potential to achieve an improvement of consciousness level after specific follow-up[1].