Nerve Cells Research Articles

CuCS/Cur composite wound dressings promote neuralized skin regeneration by rebuilding the nerve cell "factory" in deep skin burns

Regenerating skin nerves in deep burn wounds poses a significant clinical challenge. In this study, we designed an electrospun wound dressing called CuCS/Cur, which incorporates copper-doped calcium silicate (CuCS) and curcumin (Cur). The unique wound dressing releases a bioactive Cu2+-Cur chelate that plays a crucial role in addressing this challenge. By rebuilding the "factory" (hair follicle) responsible for producing nerve cells, CuCS/Cur induces a high expression of nerve-related factors within the hair follicle cells and promotes an abundant source of nerves for burn wounds. Moreover, the Cu2+-Cur chelate activates the differentiation of nerve cells into a mature nerve cell network, thereby efficiently promoting the reconstruction of the neural network in burn wounds. Additionally, the Cu2+-Cur chelate significantly stimulates angiogenesis in the burn area, ensuring ample nutrients for burn wound repair, hair follicle regeneration, and nerve regeneration. This study confirms the crucial role of chelation synergy between bioactive ions and flavonoids in promoting the regeneration of neuralized skin through wound dressings, providing valuable insights for the development of new biomaterials aimed at enhancing neural repair.

An Update on Parkinson's Disease and its Neurodegenerative Counterparts.

Neurodegenerative disorders are a group of diseases that cause nerve cell degeneration in the brain, resulting in a variety of symptoms and are not treatable with drugs. Parkinson's disease (PD), prion disease, motor neuron disease (MND), Huntington's disease (HD), spinal cerebral dyskinesia (SCA), spinal muscle atrophy (SMA), multiple system atrophy, Alzheimer's disease (AD), spinocerebellar ataxia (SCA) (ALS), pantothenate kinase-related neurodegeneration, and TDP-43 protein disorder are examples of neurodegenerative diseases. Dementia is caused by the loss of brain and spinal cord nerve cells in neurodegenerative diseases. Even though environmental and genetic predispositions have also been involved in the process, redox metal abuse plays a crucial role in neurodegeneration since the preponderance of symptoms originates from abnormal metal metabolism. Hence, this review investigates several neurodegenerative diseases that may occur symptoms similar to Parkinson's disease to understand the differences and similarities between Parkinson's disease and other neurodegenerative disorders based on reviewing previously published papers. Based on the findings, the aggregation of alpha-synuclein occurs in Parkinson's disease, multiple system atrophy, and dementia with Lewy bodies. Other neurodegenerative diseases occur with different protein aggregation or mutations. We can conclude that Parkinson's disease, Multiple system atrophy, and Dementia with Lewy bodies are closely related. Therefore, researchers must distinguish among the three diseases to avoid misdiagnosis of Multiple System Atrophy and Dementia with Lewy bodies with Parkinson's disease symptoms.

Emerging Nanotechnology for the Treatment of Alzheimer's Disease.

Nanotechnology is a great choice for medical research, and the green synthesis approach is a novel and better way to synthesize nanoparticles. Biological sources are cost-effective, environmentally friendly, and allow large-scale production of nanoparticles. Naturally obtained 3 β-hydroxy-urs-12-en-28-oic acids reported for neuroprotective and dendritic structure are reported as solubility enhancers. Plants are free from toxic substances and act as natural capping agents. In this review, the pharmacological properties of ursolic acid (UA) and the structural properties of the dendritic structure are discussed. UA acid appears to have negligible toxicity and immunogenicity, as well as favorable biodistribution, according to the current study, and the dendritic structure improves drug solubility, prevents drug degradation, increases circulation time, and potentially targets by using different pathways with different routes of administration. Nanotechnology is a field in which materials are synthesized at the nanoscale. Nanotechnology could be the next frontier of humankind's technological advancement. Richard Feynman first used the term 'Nanotechnology' in his lecture, "There is Plenty of Room at the Bottom," on 29th December, 1959, and since then, interest has increased in the research on nanoparticles. Nanotechnology is capable of helping humanity by solving major challenges, particularly in neurological disorders like Alzheimer's disease (AD), the most prevalent type, which may account for 60-70% of cases. Other significant forms of dementia include vascular dementia, dementia with Lewy bodies (abnormal protein aggregates that form inside nerve cells), and a number of illnesses that exacerbate frontotemporal dementia. Dementia is an acquired loss of cognition in several cognitive domains that are severe enough to interfere with social or professional functioning. However, dementia frequently co-occurs with other neuropathologies, typically AD with cerebrovascular dysfunction. Clinical presentations show that neurodegenerative diseases are often incurable because patients permanently lose some neurons. A growing body of research suggests that they also advance our knowledge of the processes that are probably crucial for maintaining the health and functionality of the brain. Serious neurological impairment and neuronal death are the main features of neurodegenerative illnesses, which are also extremely crippling ailments. The most prevalent neurodegenerative disorders cause cognitive impairment and dementia, and as average life expectancy rises globally, their effects become more noticeable.

Alzheimer Disease

Alzheimer's disease (AD) is typified by memory deficiencies that worsen with time, along with cognitive and behavioral abnormalities that eventually result in dementia. AD is one of the most difficult diseases to treat because of its prevalence, high cost of care, effects on patients and caregivers, and lack of mechanism-based therapies. The malfunction and loss of neurons in particular circuits and locations, especially in the populations of nerve cells supporting memory and cognition, causes the AD condition.The neuropathology of AD is characterized by intracellular and extracellular protein aggregation accumulations. In the neuronal perikarya and dystrophic neurites, abnormally phosphorylated tau forms paired helical filaments (PHFs) that combine to form neurofibrillary tangles (NFTs). The extracellular deposition of β-pleated assemblies of Aβ peptide, which result in widespread and neuritic senile plaques, is the second pathogenic hallmark.

Functional role of P2X7 purinergic receptor in cancer and cancer-related pain.

Numerous studies have revealed that the ATP-gated ion channel purinergic 2X7 receptor (P2X7R) plays an important role in tumor progression and the pathogenesis of cancer pain. P2X7R requires activation by extracellular ATP to perform its regulatory role functions. During tumor development or cancer-induced pain, ATP is released from tumor cells or other cells in the tumor microenvironment (such as tumor-associated immune cells), which activates P2X7R, opens ion channels on the cell membrane, affects intracellular molecular metabolism, and regulates the activity of tumor cells. Furthermore, peripheral organs and receptors can be damaged during tumor progression, and P2X7R expression in nerve cells (such as microglia) is significantly upregulated, enhancing sensory afferent information, sensitizing the central nervous system, and inducing or exacerbating pain. These findings reveal that the ATP-P2X7R signaling axis plays a key regulatory role in the pathogenesis of tumors and cancer pain and also has a therapeutic role. Accordingly, in this study, we explored the role of P2X7R in tumors and cancer pain, discussed the pharmacological properties of inhibiting P2X7R activity (such as the use of antagonists) or blocking its expression in the treatment of tumor and cancer pain, and provided an important evidence for the treatment of both in the future.

Non-drug therapies for patients with vibration disease associated with exposure to local vibration

Non-drug methods include acupuncture, the most effective way to regulate the body's energy system. Pulsed magnetic stimulation (PMS) is based on the application of the principles of electromagnetic induction, causes hyperpolarization or depolarization of nerve cells. The methods are practically not used in the clinic of occupational diseases, and their effectiveness in the treatment of vibration disease (VD) has not been established. The study aims to evaluate changes in the central nervous system and peripheral nerves, as well as in the psychological status of patients with vibration disease after sessions of acupuncture and pulsed magnetic stimulation. Using the acupuncture method, 24 male patients were treated with a diagnosis of VD associated with exposure to local vibration (average age 49.9±3.8 years, average length of service — 19.4±4.3 years), PMS — 24 people with a diagnosis of VD associated with exposure to local vibration (average age 48.8±3.4 years, average length of service — 18.1±3.4 years). The treatment methods performed made it possible to improve the quality of therapy, which was confirmed by a positive change in the indicators of visual and somatosensory evoked potentials, data from electroneuromyographic studies, vibration sensitivity and algesimetry, the state of the mnestic and attentional spheres of activity improved. The use of the acupuncture method allowed to improve the indicators of bioelectric activity of the brain: the amplitude of the peak N1 of visual evoked potentials increased (from 3.2 to 6.7 MV, p<0.05), the latency of the peak P200 decreased from 178.0 to 142.5 ms, p<0.05. The threshold of pain sensitivity on the zygomatic bone, on the phalanx of the 2nd finger of the hand and on the protruding part of the inner ankle decreased by 63, 125 and 250 Hz, p<0.05. Vibration sensitivity improved (on the ulnar process, phalanx of 2 fingers of the hand, p<0.01, on the tubercle of the tibia, p<0.05). Magnetic stimulation contributed to the improvement of cerebral changes in the treated patients — the latency of auditory evoked potentials decreased (p<0.03 for peak P1 and p<0.05 for peak P2), the amplitude of visual evoked potentials increased (p<0.05), the bioelectric activity of the occipital lobes of the brain increased. The duration of the afferent excitation wave at the level of the cervical region (latency N11 and N13, p<0.05) and thalamic structures (latency P25, p<0.05) increased. Non-drug therapy allowed to restore the time of excitation by the motor component of axons in patients on the upper extremities during acupuncture, on the upper and lower extremities during treatment with magnetic stimulation (p<0.05), improved indicators characterizing the mnestic-attentional and psychoemotional spheres of the treated. Ethics. Conclusion of the MEС of the Federal State Budgetary Scientific Institution "East Siberian Institute of Medical and Environmental Research" No. 32 dated 09/10/2019.

Parkinson’s Disease Recognition Using Decorrelated Convolutional Neural Networks: Addressing Imbalance and Scanner Bias in rs-fMRI Data

Parkinson’s disease (PD) is a neurodegenerative and progressive disease that impacts the nerve cells in the brain and varies from person to person. The exact cause of PD is still unknown, and the diagnosis of PD does not include a specific objective test with certainty. Although deep learning has made great progress in medical neuroimaging analysis, these methods are very susceptible to biases present in neuroimaging datasets. An innovative decorrelated deep learning technique is introduced to mitigate class bias and scanner bias while simultaneously focusing on finding distinguishing characteristics in resting-state functional MRI (rs-fMRI) data, which assists in recognizing PD with good accuracy. The decorrelation function reduces the nonlinear correlation between features and bias in order to learn bias-invariant features. The publicly available Parkinson’s Progression Markers Initiative (PPMI) dataset, referred to as a single-scanner imbalanced dataset in this study, was used to validate our method. The imbalanced dataset problem affects the performance of the deep learning framework by overfitting to the majority class. To resolve this problem, we propose a new decorrelated convolutional neural network (DcCNN) framework by applying decorrelation-based optimization to convolutional neural networks (CNNs). An analysis of evaluation metrics comparisons shows that integrating the decorrelation function boosts the performance of PD recognition by removing class bias. Specifically, our DcCNN models perform significantly better than existing traditional approaches to tackle the imbalance problem. Finally, the same framework can be extended to create scanner-invariant features without significantly impacting the performance of a model. The obtained dataset is a multiscanner dataset, which leads to scanner bias due to the differences in acquisition protocols and scanners. The multiscanner dataset is a combination of two publicly available datasets, namely, PPMI and FTLDNI—the frontotemporal lobar degeneration neuroimaging initiative (NIFD) dataset. The results of t-distributed stochastic neighbor embedding (t-SNE) and scanner classification accuracy of our proposed feature extraction–DcCNN (FE-DcCNN) model validated the effective removal of scanner bias. Our method achieves an average accuracy of 77.80% on a multiscanner dataset for differentiating PD from a healthy control, which is superior to the DcCNN model trained on a single-scanner imbalanced dataset.

Light‐Driven Micronavigators for Directional Migration of Cells

AbstractCell migration is an essential physiological process in the life cycle of cells, playing a crucial role in cancer metastasis, neural development, and cellular immune response. However, achieving precise control of cell migration at single‐cell level is challenging due to the intricate and diverse microenvironments of cells. Here, an optical technique is presented that utilizes light‐actuated micronavigators to guide the directional migration of individual cells both in vitro and in vivo. Employing high‐speed scanning optical tweezers, micronavigators near target cells are trapped and rotated at a rotation speed of up to 12 000 rpm, which, to the best of knowledge, represents the fastest rotation of light‐driven micromotors in a biological environment to date. The micronavigators generate a powerful fluid shear force (up to 40 pN) which can guide the migration of immune and nerve cells in a predetermined direction. Furthermore, micronavigators are employed to guide cell migration in various biological systems, including lab‐on‐a‐chip devices and blood vessels within living animals. This technique offers new opportunities for controlling cell migration, enabling precise immune activation, and neuron repair at the single‐cell level.

Microglia-derived exosomes selective sorted by YB-1 alleviate nerve damage and cognitive outcome in Alzheimer’s disease

BackgroundNeuroinflammation is a characteristic pathological change of Alzheimer’s Diseases (AD). Microglia have been reported to participate in inflammatory responses within the central nervous system. However, the mechanism of microglia released exosome (EXO) contribute to communication within AD microenvironment remains obscure.MethodsThe interaction between microglia and AD was investigated in vitro and in vivo. RNA-binding protein immunoprecipitation (RIP) was used to investigate the mechanisms of miR-223 and YB-1. The association between microglia derived exosomal YB-1/miR-223 axis and nerve cell damage were assessed using Western blot, immunofluorescence, RT-PCR, ELISA and wound healing assay.ResultsHere, we reported AD model was responsible for the M1-like (pro-inflammatory) polarization of microglia which in turn induced nerve cell damage. While M2-like (anti-inflammatory) microglia could release miR-223-enriched EXO which reduced neuroinflammation and ameliorated nerve damage in AD model in vivo and in vitro. Moreover, YB-1 directly interacted with miR-223 both in cell and EXO, and participated in microglia exosomal miR-223 loading.ConclusionThese results indicate that anti-inflammatory microglia-mediated neuroprotection form inflammatory damage involves exporting miR-223 via EXO sorted by YB-1. Consequently, YB-1-mediated microglia exosomal sorting of miR-223 improved the nerve cell damage repair, representing a promising therapeutic target for AD.

Surface modified PLGA nanoparticles of gabapentin: Biodistribution and pharmacodynamic investigation via intranasal route

Epilepsy is a chronic condition and is caused by abnormal electrical conduction by nerve cells. It can affect people from different age groups. The prime objective of epilepsy therapeutics is the targeted and sustained release of drugs at the site of action i.e. in the brain. In the present study, PLGA nanoparticles of gabapentin, coated with Polysorbate 80 were prepared with the aim of delivering the drug to the brain through the nasal route. The said nanoparticles were formulated by the method of double emulsion and solvent evaporation. Thereafter, the prepared nanoparticles were characterized for particle size, Zeta potential, and Surface morphology of the nanoparticles was evaluated by SEM &TEM In vitro release in PBS (pH 7.4) and SNF (pH 5.5). In addition, FTIR and DSC techniques were used to confirm the P80 coating around the nanoparticle's surface. In vitro, cell assays like Cytotoxicity studies, and quantitative and qualitative cell uptake studies were studied on Neuro-2a cells. The nasal mucosa of the goat was used to perform histopathological studies to evaluate the toxicity of nanoparticles. A biodistribution study was performed on Swiss albino mice and the results showed that the concentration of the drug reaching the brain in the case of P80 modified nanoparticles was maximum as compared to Plain PLGA nanoparticle, and aqueous solution of the drug. Pharmacodynamic studies were performed to assess the delay in different phases of convulsion and the results showed that the modified nanoparticles of gabapentin were able to significantly delay the episodes of convulsion. Overall, results demonstrate that modified nanoparticles are potential drug carriers in the brain for the management of epilepsy.

Desensitizing the autonomic nervous system to mitigate anti-GD2 monoclonal antibody side effects

BackgroundAnti-GD2 monoclonal antibodies (mAbs) have shown to improve the overall survival of patients with high-risk neuroblastoma (HR-NB). Serious adverse events (AEs), including pain, within hours of antibody infusion, have limited the development of these therapies. In this study, we provide evidence of Autonomic Nervous System (ANS) activation as the mechanism to explain the main side effects of anti-GD2 mAbs.MethodsThrough confocal microscopy and computational super-resolution microscopy experiments we explored GD2 expression in postnatal nerves of infants. In patients we assessed the ANS using the Sympathetic Skin Response (SSR) test. To exploit tachyphylaxis, a novel infusion protocol (the Step-Up) was mathematically modelled and tested.ResultsThrough confocal microscopy, GD2 expression is clearly visible in the perineurium surrounding the nuclei of nerve cells. By computational super-resolution microscopy experiments we showed the selective expression of GD2 on the cell membranes of human Schwann cells in peripheral nerves (PNs) significantly lower than on NB. In patients, changes in the SSR were observed 4 minutes into the anti-GD2 mAb naxitamab infusion. SSR latency quickly shortened followed by gradual decrease in the amplitude before disappearance. SSR response did not recover for 24 hours consistent with tachyphylaxis and absence of side effects in the clinic. The Step-Up protocol dissociated on-target off-tumor side effects while maintaining serum drug exposure.ConclusionWe provide first evidence of the ANS as the principal non-tumor target of anti-GD2 mAbs in humans. We describe the development and modeling of the Step-Up protocol exploiting the tachyphylaxis phenomenon we demonstrate in patients using the SSR test.

An injectable refrigerated hydrogel for inducing local hypothermia and neuroprotection against traumatic brain injury in mice

BackgroundHypothermia is a promising therapy for traumatic brain injury (TBI) in the clinic. However, the neuroprotective outcomes of hypothermia-treated TBI patients in clinical studies are inconsistent due to several severe side effects. Here, an injectable refrigerated hydrogel was designed to deliver 3-iodothyronamine (T1AM) to achieve a longer period of local hypothermia for TBI treatment. Hydrogel has four advantages: (1) It can be injected into injured sites after TBI, where it forms a hydrogel and avoids the side effects of whole-body cooling. (2) Hydrogels can biodegrade and be used for controlled drug release. (3) Released T1AM can induce hypothermia. (4) This hydrogel has increased medical value given its simple operation and ability to achieve timely treatment.MethodsPol/T hydrogels were prepared by a low-temperature mixing method and characterized. The effect of the Pol/T hydrogel on traumatic brain injury in mice was studied. The degradation of the hydrogel at the body level was observed with a small animal imager. Brain temperature and body temperature were measured by brain thermometer and body thermometer, respectively. The apoptosis of peripheral nerve cells was detected by immunohistochemical staining. The protective effect of the hydrogels on the blood–brain barrier (BBB) after TBI was evaluated by the Evans blue penetration test. The protective effect of hydrogel on brain edema after injury in mice was detected by Magnetic resonance (MR) in small animals. The enzyme linked immunosorbent assay (ELISA) method was used to measure the levels of inflammatory factors. The effects of behavioral tests on the learning ability and exercise ability of mice after injury were evaluated.ResultsThis hydrogel was able to cool the brain to hypothermia for 12 h while maintaining body temperature within the normal range after TBI in mice. More importantly, hypothermia induced by this hydrogel leads to the maintenance of BBB integrity, the prevention of cell death, the reduction of the inflammatory response and brain edema, and the promotion of functional recovery after TBI in mice. This cooling method could be developed as a new approach for hypothermia treatment in TBI patients.ConclusionOur study showed that injectable and biodegradable frozen Pol/T hydrogels to induce local hypothermia in TBI mice can be used for the treatment of traumatic brain injury.Graphical

Pilot study with randomised control of dual site theta burst transcranial magnetic stimulation (TMS) for methamphetamine use disorder: a protocol for the TARTAN study

BackgroundTranscranial magnetic stimulation (TMS) (including the theta burst stimulation (TBS) form of TMS used in this study) is a non-invasive means to stimulate nerve cells in superficial areas of the brain. In recent years, there has been a growth in the application of TMS to investigate the modulation of neural networks involved in substance use disorders. This study examines the feasibility of novel TMS protocols for the treatment of methamphetamine (MA) use disorder in an ambulatory drug and alcohol treatment setting.MethodsThirty participants meeting the criteria for moderate to severe MA use disorder will be recruited in community drug and alcohol treatment settings and randomised to receive active TMS or sham (control) intervention. The treatment is intermittent TBS (iTBS) applied to the left dorsolateral prefrontal cortex (DLPFC), then continuous TBS (cTBS) to the left orbitofrontal cortex (OFC). Twelve sessions are administered over 4 weeks with opt-in weekly standardized cognitive behaviour therapy (CBT) counselling and a neuroimaging sub-study offered to participants. Primary outcomes are feasibility measures including recruitment, retention and acceptability of the intervention. Secondary outcomes include monitoring of safety and preliminary efficacy data including changes in substance use, cravings (cue reactivity) and cognition (response inhibition).DiscussionThis study examines shorter TBS protocols of TMS for MA use disorder in real-world drug and alcohol outpatient settings where withdrawal and abstinence from MA, or other substances, are not eligibility requirements. TMS is a relatively affordable treatment and staff of ambulatory health settings can be trained to administer TMS. It is a potentially scalable and translatable treatment for existing drug and alcohol clinical settings. TMS has the potential to provide a much-needed adjuvant treatment to existing psychosocial interventions for MA use disorder. A limitation of this protocol is that the feasibility of follow-up is only examined at the end of treatment (4 weeks).Trial registrationAustralia New Zealand Clinical Trial Registry ACTRN12622000762752. Registered on May 27, 2022, and retrospectively registered (first participant enrolled) on May 23, 2022, with protocol version 7 on February 24, 2023.

Inhibiting the SARM1-NAD+ axis reduces oxidative stress-induced damage to retinal and nerve cells

Retinal neurodegenerative diseases are a category of refractory blinding eye conditions closely associated with oxidative stress induced by mitochondrial dysfunction in retinal cells. SARM1, a core driver molecule leading to axonal degeneration, possesses NAD+ enzyme (NADase) activity. However, the role of the SARM1-NAD+ axis in oxidative stress-induced retinal cell death remains unclear. Here, we employed the SARM1 NADase inhibitor DSRM-3716 and established a glucose oxidase (GOx)-induced oxidative stress cell model. We found that compared to the GOx group, the DSRM-3716 pre-treated group reduced the hydrolysis of NAD+, inhibited the elevation of oxidative stress markers induced by GOx, decreased mitochondrial dysfunction, lowered the phosphorylation level of JNK, and attenuated the occurrence of pyroptosis in retinal and nerve cells, thereby providing protection for neurite growth. Further utilization of the JNK activator Anisomycin activated JNK, revealed that the JNK/c-Jun pathway down-regulated NMNAT2 expression. Consequently, it reduced cellular NAD+ synthesis, exacerbated mitochondrial dysfunction and cell pyroptosis, and reversed the protective effect of DSRM-3716 on cells. In summary, the inhibition of SARM1 NADase activity substantially mitigates oxidative damage to retinal cells and mitochondrial damage. Additionally, JNK simultaneously serves as both an upstream and downstream regulator in the SARM1-NAD+ axis, regulating retinal cell pyroptosis and neurite injury. Thus, this study provides new insights into the pathological processes of retinal cell oxidative stress and identifies potential therapeutic targets for retinal neurodegenerative diseases.

Schisandrol A, the Major Active Constitute in Schisandra chinensis: A Review of Its Preparation, Biological Activities, and Pharmacokinetics Analysis.

Schisandra chinensis (S. chinensis) has a long history as a traditional Chinese medicine that is astringent, beneficial to vital energy, tonifies the kidney, tranquilizes the heart, etc. Significantly, Schisandrol A (SA) is extracted from S. chinensis and shows surprising and satisfactory biological activity, including anti-inflammatory, hepatoprotective, cardiovascular protection, and antitumor properties, among others. SA has a more pronounced protective effect on central damaged nerves among its numerous pharmacological effects, improving neurodegenerative diseases such as Alzheimer's and Parkinson's through the protection of damaged nerve cells and the enhancement of anti-oxidant capacity. Pharmacokinetic studies have shown that SA has a pharmacokinetic profile with a rapid absorption, wide distribution, maximal concentration in the liver, and primarily renal excretion. However, hepatic and intestinal first-pass metabolism can affect SA's bioavailability. In addition, the content of SA, as an index component of S. chinensis Pharmacopoeia, should not be less than 0.40%, and the content of SA in S. chinensis compound formula was determined with the help of high-performance liquid chromatography (HPLC), which is a stable and reliable method, and it can lay a foundation for the subsequent quality control. Therefore, this paper systematically reviews the preparation, pharmacological effects, pharmacokinetic properties, and content determination of SA with the goal of updating and deepening the understanding of SA, as well as providing a theoretical basis for the study of SA at a later stage.

Crosstalk Between Cell Death and Spinal Cord Injury: Neurology and Therapy.

Spinal cord injury (SCI) often leads to neurological dysfunction, and neuronal cell death is one of the main causes of neurological dysfunction. After SCI, in addition to necrosis, programmed cell death (PCD) occurs in nerve cells. At first, studies recognized only necrosis, apoptosis, and autophagy. In recent years, researchers have identified new forms of PCD, including pyroptosis, necroptosis, ferroptosis, and cuproptosis. Related studies have confirmed that all of these cell death modes are involved in various phases of SCI and affect the direction of the disease through different mechanisms and pathways. Furthermore, regulating neuronal cell death after SCI through various means has been proven to be beneficial for the recovery of neural function. In recent years, emerging therapies for SCI have also provided new potential methods to restore neural function. Thus, the relationship between SCI and cell death plays an important role in the occurrence and development of SCI. This review summarizes and generalizes the relevant research results on neuronal necrosis, apoptosis, autophagy, pyroptosis, necroptosis, ferroptosis, and cuproptosis after SCI to provide a new understanding of neuronal cell death after SCI and to aid in the treatment of SCI.

Low back pain: justification of treatment standards (literature review)

Low back pain: justification of treatment standards (literature review)

Dopamine and its precursor levodopa inactivate SARS-CoV-2 main protease by forming a quinoprotein

Many studies show either the absence, or very low levels of, SARS-CoV-2 viral RNA and/or antigen in the brain of COVID-19 patients. Reports consistently indicate an abortive infection phenomenon in nervous cells despite the fact that they contain the SARS-CoV-2 receptor, ACE2. Dopamine levels in different brain regions are in the range of micromolar to millimolar concentrations. We have shown that sub-micromolar to low micromolar concentrations of dopamine or its precursor (levodopa) time- and dose-dependently inhibit the activity of SARS-CoV-2 main protease (Mpro), which is vital for the viral life cycle, by forming a quinoprotein. Thiol detection coupled with the assessment of Mpro activity suggests that among the 12 cysteinyl thiols, the active site, Cys145-SH, is preferentially conjugated to the quinone derived from the oxidation of dopamine or levodopa. LC-MS/MS analyses show that the Cys145-SH is covalently conjugated by dopamine- or levodopa-o-quinone. These findings help explain why SARS-CoV-2 causes inefficient replication in many nerve cell lines. It is well recognized that inhaled pulmonary drug delivery is the most robust therapy pathway for lung diseases. CVT-301 (orally inhaled levodopa) was approved by the FDA as a drug for Parkinson's patients prior to the outbreak of COVID-19 in 2018. Based on the fact that SARS-CoV-2 causes inefficient replication in the CNS with abundant endogenous Mpro inhibitor in addition to the current finding that levodopa has an Mpro-inhibitory effect somewhat stronger than dopamine, we should urgently investigate the use of CVT-301 as a lung-targeting, COVID-19, Mpro inhibitor.

The regulation of BAI1 in astrocytes through the STAT3/EZH2 axis relieves neuronal apoptosis in rats with Alzheimer’s disease

Alzheimer’s disease (AD) is a common neurodegenerative disease. Previous studies have identified the critical role of astrocytes in the progression of AD. The focus of this study revolves around clarifying the regulatory mechanism of the STAT3/EZH2/BAI1 axis in astrocytes in AD. We successfully developed a rat model of AD, and measured the learning and cognitive ability of the rats by Morris water maze experiment. HE and Nissl’s staining were used for histomorphological identification of the rat hippocampus. Meanwhile, immunofluorescence and immunohistochemistry were used to detect astrocyte activation and brain-specific angiogenesis inhibitor-1 (BAI1) expression in rat hippocampal tissue, respectively. The role of STAT3/EZH2/BAI1 regulating axis in astrocyte activation and neuronal cell apoptosis was verified by establishing the co-culture system of astrocytes and nerve cells in vitro. Western Blot (WB) was used to detect the expression of associated proteins, and enzyme-linked immunosorbent assay (ELISA) was used to detect astrocyte neurotrophic factor secretion. Hochest/PI staining and flow cytometry were used to observe neuronal apoptosis. Compared with the sham group, AD rats showed significantly decreased cognitive and learning abilities, noticeable hippocampal tissue damage, and significantly low levels of BAI1 expression. In in vitro models, BAI1 was found to inhibit astrocyte activation and enhance the secretion of neurotrophins, resulting in decrease of neurone apoptosis. The regulation of BAI1 by the STAT3/EZH2 axis was shown to affect astrocyte activation and neuronal cell apoptosis. In conclusion, this study represents the pioneering discovery that regulated by the STAT3/EZH2 axis, BAI1 suppresses astrocyte activation, thus reducing neuronal apoptosis.

The relationship between optic nerve and Onodi cells on CT scan

The Onodi cells, also known as sphenoethmoidal air cells, are a variant of the most posterior ethmoid cells and are closely related to the optic canal. The presence of Onodi cells may increase the risk of optic nerve injury and result in confusion with sphenoid sinuses during endoscopic sinus surgery, leading to the oversight of sphenoid sinus pathology. The aim of the study was to examine the characteristics of Onodi cells and their relationship with the optic nerve on CT scans. A cross-sectional study was conducted, analyzing CT scans of paranasal sinuses in 196 posterior ethmoid air cells from 98 patients (30 males and 68 females) aged 18 or older, without abnormalities in the paranasal sinuses and optic nerve anatomy. The prevalence of Onodi cells was 38.78%, with 26.32% on the left, 44.74% on the right, and 28.94% bilaterally. Onodi cell pneumatization was observed in the order of Type I > Type II > Type III on both sides. The most common relationship between Onodi cells and the optic nerve was Type A on both sides. The incidence of the optic nerve bulging into Onodi cells was 50%, and the exposure of the optic nerve into Onodi cells was 7.89%. The study investigated the prevalence and relationship between Onodi cells and the optic nerve. CT scans proved to be a crucial diagnostic tool in providing essential information about Onodi cells before surgery.