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Cells Jun 2024Oligodendrocyte progenitor cells (OPCs) represent a subtype of glia, giving rise to oligodendrocytes, the myelin-forming cells in the central nervous system (CNS). While... (Review)
Review
Oligodendrocyte progenitor cells (OPCs) represent a subtype of glia, giving rise to oligodendrocytes, the myelin-forming cells in the central nervous system (CNS). While OPCs are highly proliferative during development, they become relatively quiescent during adulthood, when their fate is strictly influenced by the extracellular context. In traumatic injuries and chronic neurodegenerative conditions, including those of autoimmune origin, oligodendrocytes undergo apoptosis, and demyelination starts. Adult OPCs become immediately activated; they migrate at the lesion site and proliferate to replenish the damaged area, but their efficiency is hampered by the presence of a glial scar-a barrier mainly formed by reactive astrocytes, microglia and the deposition of inhibitory extracellular matrix components. If, on the one hand, a glial scar limits the lesion spreading, it also blocks tissue regeneration. Therapeutic strategies aimed at reducing astrocyte or microglia activation and shifting them toward a neuroprotective phenotype have been proposed, whereas the role of OPCs has been largely overlooked. In this review, we have considered the glial scar from the perspective of OPCs, analysing their behaviour when lesions originate and exploring the potential therapies aimed at sustaining OPCs to efficiently differentiate and promote remyelination.
Topics: Humans; Remyelination; Animals; Oligodendrocyte Precursor Cells; Cicatrix; Neuroglia; Oligodendroglia; Myelin Sheath; Cell Differentiation
PubMed: 38920654
DOI: 10.3390/cells13121024 -
Drug Design, Development and Therapy 2024Ciprofol is a recently developed short-acting gamma-aminobutyric acid receptor agonist with a higher potency than that of propofol. As a new sedative drug, there are few... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study Clinical Trial
Comparison of Ciprofol-Based and Propofol-Based Total Intravenous Anesthesia on Microvascular Decompression of Facial Nerve with Neurophysiological Monitoring: A Randomized Non-Inferiority Trial.
PURPOSE
Ciprofol is a recently developed short-acting gamma-aminobutyric acid receptor agonist with a higher potency than that of propofol. As a new sedative drug, there are few clinical studies on ciprofol. We sought to examine the safety and efficacy of ciprofol use for general anesthesia in neurosurgical individuals undergoing neurosurgical surgery with intraoperative neurophysiological monitoring (IONM).
PATIENTS AND METHODS
This single-center, non-inferiority, single-blind, randomized controlled trial was conducted from September 13, 2022 to September 22, 2023. 120 patients undergoing elective microvascular decompression surgery (MVD) with IONM were randomly assigned to receive either ciprofol or propofol. The primary outcome of this study was the amplitude of intraoperative compound muscle action potential decline, and the secondary outcome included the indexes related to neurophysiological monitoring and anesthesia outcomes.
RESULTS
The mean values of the primary outcome in the ciprofol group and the propofol group were 64.7±44.1 and 53.4±35.4, respectively. Furthermore, the 95% confidence interval of the difference was -25.78 to 3.12, with the upper limit of the difference being lower than the non-inferiority boundary of 6.6. Ciprofol could achieve non-inferior effectiveness in comparison with propofol in IONM of MVD. The result during anesthesia induction showed that the magnitude of the blood pressure drop and the incidence of injection pain in the ciprofol group were significantly lower than those in the propofol group (P<0.05). The sedative drug and norepinephrine consumption in the ciprofol group was significantly lower than that in the propofol group (P<0.05).
CONCLUSION
Ciprofol is not inferior to propofol in the effectiveness and safety of IONM and the surgical outcome. Concurrently, ciprofol is more conducive to reducing injection pain and improving hemodynamic stability, which may be more suitable for IONM-related surgery, and has a broad application prospect.
Topics: Humans; Propofol; Male; Middle Aged; Female; Single-Blind Method; Microvascular Decompression Surgery; Intraoperative Neurophysiological Monitoring; Facial Nerve; Anesthesia, Intravenous; Anesthetics, Intravenous; Aged; Adult
PubMed: 38919963
DOI: 10.2147/DDDT.S459618 -
Neuropsychiatric Disease and Treatment 2024We aimed to investigate the efficacy of a combined herbal formula and electroacupuncture (EA) for mild cognitive impairment (MCI), a neurodegenerative disease leading to...
PURPOSE
We aimed to investigate the efficacy of a combined herbal formula and electroacupuncture (EA) for mild cognitive impairment (MCI), a neurodegenerative disease leading to dementia, and its underlying mechanisms of action.
PATIENTS AND METHODS
This was a prospective open-label observational pilot study at Daejeon Korean Medicine Hospital of Daejeon University in South Korea from March 2022 to March 2023. We included six Korean patients (50% male) aged ≥ 45 years and < 85 years with MCI, a clinical dementia rating score of 0.5, and a Montreal Cognitive Assessment-Korea (MoCA-K) score ≤ 22. The exclusion criterion was impaired cognitive function. Patients received combined therapy, including a herbal formula and EA, for 12-24 weeks. We prescribed the herbal formulas Gamiguibi-tang, Yukmijihwang-tang, and Banhasasim-tang to the patients for at least 70% of the treatment period, in combination with EA. Moreover, we investigated changes in cognitive and cognition-related symptoms and cytokine expression in the blood following combined traditional medicine therapy. At baseline and after 12 and 24 weeks, we administered the MoCA-K and cognitive-related questionnaires. We analyzed network pharmacology to reflect the herbal formula intervention mechanism comprehensively.
RESULTS
The median score [interquartile range] of MoCA-K at baseline was 19.5 [16.0, 22.0], which improved significantly (24.5 [24.0, 26.0], < 0.01) over 24 weeks following combined therapy. We obtained no significant conclusion regarding cytokine changes due to the small sample size. In network pharmacology, we analyzed the brain, head, heart, peripheral nerves, peripheral nervous system, and pancreas as the enriched organs from the common targets of the three herbal formulas.
CONCLUSION
Combined herbal medicine and EA improved cognitive function in patients with MCI. We assume the underlying mechanism of herbal formulas to be antioxidative and anti-inflammatory changes in cytokine expression. Combined traditional medicine has potential therapeutic application in preventing MCI progression to dementia.
PubMed: 38919562
DOI: 10.2147/NDT.S465650 -
Journal of Anaesthesiology, Clinical... 2024Spinal and epidural blocks are commonly employed for pain relief during and following cesarean section. Intrathecal morphine (ITM) has been the gold standard for the... (Review)
Review
Spinal and epidural blocks are commonly employed for pain relief during and following cesarean section. Intrathecal morphine (ITM) has been the gold standard for the same for many years. In recent times, many peripheral nerve blocks (PNBs) have been tried for postoperative analgesia following cesarean delivery (PACD). This article has reviewed the common PNBs used for PACD. The role of PNBs along with ITM has been studied and the current best strategy for PACD has also been explored. Currently, Ilio-inguinal nerve and anterior transversus abdominis plane block in conjunction with intrathecal morphine have been found to be the most effective strategy, providing lower rest pain at 6 hours as compared to ITM alone. In patients not receiving intrathecal morphine, recommended PNBs are lateral transversus abdominis plane block, single shot local anesthetic wound infiltration, or continuous wound infiltration with catheter below rectus fascia. PNBs are recommended for PACD. They have an opioid-sparing effect and are devoid of adverse effects associated with central neuraxial blocks such as hypotension, bradycardia, and urine retention. However, caution must be observed with PNBs for possible local anesthetic toxicity due to the large volumes of drug required.
PubMed: 38919417
DOI: 10.4103/joacp.joacp_204_22 -
The Iowa Orthopaedic Journal 2024Periacetabular osteotomy (PAO) is a well-established surgical treatment for hip dysplasia, but very few studies report the impact of peri-operative management strategies... (Review)
Review
BACKGROUND
Periacetabular osteotomy (PAO) is a well-established surgical treatment for hip dysplasia, but very few studies report the impact of peri-operative management strategies on early pain and function. The purpose of this study is to describe peri-operative management variability among a group of experienced surgeons and review the literature supporting these practice patterns.
METHODS
We surveyed 16 surgeons that perform PAO to document various aspects of peri-operative management at four stages: pre-operative, intra-operative, post-operative in the hospital, and at discharge. Our goal was to report current surgical pain management strategies, adjunct medications, type of anesthesia, deep venous thrombosis and heterotopic ossification prophylaxis strategies, initiation of physical therapy, and use of continuous passive motion (CPM). We reviewed current literature to identify studies supporting these perioperative strategies and identify knowledge gaps that would benefit from further investigation.
RESULTS
Of the 16 surgeons surveyed, 75% had been in practice greater than 10 years and most had not altered their post-operative protocol for more than 3 years. 15/16 surgeons felt that length of stay could be reduced at their institution with improved peri-operative pain management. 6/16 were considering or had already implemented outpatient PAO as a part of their practice. We found significant variability in the pain medications provided at all peri-operative stages. 14/16 utilized general anesthesia, and many utilized epidural or peripheral nerve blocks. 6/16 surgeons utilized surgical field block (also referred to as periarticular block). These surgeons advocated that surgical field block was an effective intervention with no/minimal complication risk. There is very little literature critically evaluating efficacy of these perioperative management strategies for PAO.
CONCLUSION
There is significant practice variability in peri-operative management of PAO surgery. We report various strategies utilized by a group of experienced surgeons and review supporting literature. There are significant knowledge gaps in best surgical pain management strategies, adjunct medications, surgical field blocks, and use of CPM that need further investigation. .
Topics: Humans; Osteotomy; Acetabulum; Perioperative Care; Practice Patterns, Physicians'; Pain Management; Hip Dislocation; Pain, Postoperative
PubMed: 38919350
DOI: No ID Found -
Cureus May 2024Neuropathic pain (NP), arising from dysfunction in the neurological system, poses a significant challenge in pain management due to its intricate origin and... (Review)
Review
Neuropathic pain (NP), arising from dysfunction in the neurological system, poses a significant challenge in pain management due to its intricate origin and unpredictable response to conventional treatments. Electroanalgesia, a collection of techniques such as transcutaneous electric nerve stimulation (TENS), peripheral electrical nerve stimulation (PENS), spinal cord stimulation (SCS), deep brain stimulation (DBS), and electroacupuncture (EA), presents a potential alternative or complementary approach. This review brings together evidence from 56 studies to evaluate the effectiveness and safety of electroanalgesia in chronic NP. It discusses the mechanisms underlying NP, the indications for electroanalgesia, and the techniques utilized, emphasizing the diverse applications and potential benefits. However, despite its potential uses, electroanalgesia has its limitations, including variable effectiveness and potential adverse effects. Furthermore, the review recognizes the limitations of the methodology and the need for further research to refine treatment protocols and enhance the understanding of electroanalgesia's role in comprehensive pain management strategies.
PubMed: 38919207
DOI: 10.7759/cureus.61122 -
Journal of Nanobiotechnology Jun 2024Active artificial bone substitutes are crucial in bone repair and reconstruction. Calcium phosphate bone cement (CPC) is known for its biocompatibility, degradability,...
Active artificial bone substitutes are crucial in bone repair and reconstruction. Calcium phosphate bone cement (CPC) is known for its biocompatibility, degradability, and ability to fill various shaped bone defects. However, its low osteoinductive capacity limits bone regeneration applications. Effectively integrating osteoinductive magnesium ions with CPC remains a challenge. Herein, we developed magnesium malate-modified CPC (MCPC). Incorporating 5% magnesium malate significantly enhances the compressive strength of CPC to (6.18 ± 0.49) MPa, reduces setting time and improves disintegration resistance. In vitro, MCPC steadily releases magnesium ions, promoting the proliferation of MC3T3-E1 cells without causing significant apoptosis, proving its biocompatibility. Molecularly, magnesium malate prompts macrophages to release prostaglandin E2 (PGE2) and synergistically stimulates dorsal root ganglion (DRG) neurons to synthesize and release calcitonin gene-related peptide (CGRP). The CGRP released by DRG neurons enhances the expression of the key osteogenic transcription factor Runt-related transcription factor-2 (RUNX2) in MC3T3-E1 cells, promoting osteogenesis. In vivo experiments using minipig vertebral bone defect model showed MCPC significantly increases the bone volume fraction, bone density, new bone formation, and proportion of mature bone in the defect area compared to CPC. Additionally, MCPC group exhibited significantly higher levels of osteogenesis and angiogenesis markers compared to CPC group, with no inflammation or necrosis observed in the hearts, livers, or kidneys, indicating its good biocompatibility. In conclusion, MCPC participates in the repair of bone defects in the complex post-fracture microenvironment through interactions among macrophages, DRG neurons, and osteoblasts. This demonstrates its significant potential for clinical application in bone defect repair.
Topics: Animals; Calcium Phosphates; Bone Cements; Mice; Swine; Calcitonin Gene-Related Peptide; Osteogenesis; Swine, Miniature; Bone Regeneration; Spine; Ganglia, Spinal; Cell Line; Magnesium
PubMed: 38918787
DOI: 10.1186/s12951-024-02595-1 -
PloS One 2024Orexin-mediated stimulation of orexin receptors 1/2 (OX[1/2]R) may stimulate the diaphragm and genioglossus muscle via activation of inspiratory neurons in the...
Orexin receptor 2 agonist activates diaphragm and genioglossus muscle through stimulating inspiratory neurons in the pre-Bötzinger complex, and phrenic and hypoglossal motoneurons in rodents.
Orexin-mediated stimulation of orexin receptors 1/2 (OX[1/2]R) may stimulate the diaphragm and genioglossus muscle via activation of inspiratory neurons in the pre-Bötzinger complex, which are critical for the generation of inspiratory rhythm, and phrenic and hypoglossal motoneurons. Herein, we assessed the effects of OX2R-selective agonists TAK-925 (danavorexton) and OX-201 on respiratory function. In in vitro electrophysiologic analyses using rat medullary slices, danavorexton and OX-201 showed tendency and significant effect, respectively, in increasing the frequency of inspiratory synaptic currents of inspiratory neurons in the pre-Bötzinger complex. In rat medullary slices, both danavorexton and OX-201 significantly increased the frequency of inspiratory synaptic currents of hypoglossal motoneurons. Danavorexton and OX-201 also showed significant effect and tendency, respectively, in increasing the frequency of burst activity recorded from the cervical (C3-C5) ventral root, which contains axons of phrenic motoneurons, in in vitro electrophysiologic analyses from rat isolated brainstem-spinal cord preparations. Electromyogram recordings revealed that intravenous administration of OX-201 increased burst frequency of the diaphragm and burst amplitude of the genioglossus muscle in isoflurane- and urethane-anesthetized rats, respectively. In whole-body plethysmography analyses, oral administration of OX-201 increased respiratory activity in free-moving mice. Overall, these results suggest that OX2R-selective agonists enhance respiratory function via activation of the diaphragm and genioglossus muscle through stimulation of inspiratory neurons in the pre-Bötzinger complex, and phrenic and hypoglossal motoneurons. OX2R-selective agonists could be promising drugs for various conditions with respiratory dysfunction.
Topics: Animals; Diaphragm; Motor Neurons; Orexin Receptors; Rats; Phrenic Nerve; Mice; Male; Hypoglossal Nerve; Rats, Sprague-Dawley; Inhalation; Medulla Oblongata; Isoquinolines; Pyridines
PubMed: 38917189
DOI: 10.1371/journal.pone.0306099 -
International Journal of... Apr 2024Leprosy, caused by the bacterium Mycobacterium leprae, is known to primarily affect the skin and peripheral nerves. We present a rare case of leprosy initially...
Leprosy, caused by the bacterium Mycobacterium leprae, is known to primarily affect the skin and peripheral nerves. We present a rare case of leprosy initially manifesting as demyelinating polyneuropathy. A 46-year-old female presented with progressive weakness, tingling, and numbness in her extremities. Nerve conduction studies revealed evidence of demyelination, prompting further investigations. Skin slit-skin smears confirmed the diagnosis of leprosy, with the presence of acid-fast bacilli. The patient was subsequently started on multidrug therapy, leading to significant clinical improvement. This case highlights the importance of considering leprosy as a differential diagnosis in patients presenting with demyelinating polyneuropathy, especially in endemic regions.
Topics: Humans; Female; Middle Aged; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Leprosy; Diagnosis, Differential; Mycobacterium leprae; Skin; Leprostatic Agents
PubMed: 38916395
DOI: 10.4103/ijmy.ijmy_39_24 -
Drug Design, Development and Therapy 2024Nerve injury is a serious complication of percutaneous endoscopic transforaminal lumbar discectomy due to nerve root contact. The maximum tolerable concentration (MTC)...
Determining the Maximum Tolerable Concentration of Ropivacaine to Maintain Sensation of the Nerve Root in Percutaneous Endoscopic Transforaminal Lumbar Discectomy: Can Epidural Anaesthesia Achieve Pain-Tactile Separation Block to Avoid Nerve Injury?
INTRODUCTION
Nerve injury is a serious complication of percutaneous endoscopic transforaminal lumbar discectomy due to nerve root contact. The maximum tolerable concentration (MTC) of ropivacaine concentration for epidural anaesthesia, is defined as the concentration that minimises pain while preserving the sensation of the nerve roots. This distinct advantage allows the patient to provide feedback to the surgeon when the nerve roots are contacted.
METHODS
We used a biased-coin design to determine the MTC, which was estimated by the 10% effective concentration (EC), ie, the concentration at which 10% of patients lost sensation in the nerve roots. The determinant for positive response was lack of sensory feedback upon contact with the nerve root, and the feedback from occurrence of sensations in the innervation area upon contact with the nerve root was defined as a negative response. Primary outcome was the response from contact nerve root. Secondary outcomes were the type and number of statements of negative response and each patient's pain score during surgery.
RESULTS
Fifty-four patients were included in this study. The EC was 0.434% (95% CI: 0.410%, 0.440%) using isotonic regression in comparison with 0.431% (95% CI: 0.399%, 0.444%) using probit regression. Three type statements of negative response were reported including "tactile sensation", radiculalgia, and numbness.
CONCLUSION
The MTC of ropivacaine used for epidural anaesthesia was 0.434% to avoid nerve injury in percutaneous endoscopic transforaminal lumbar discectomy.
Topics: Ropivacaine; Humans; Male; Middle Aged; Female; Lumbar Vertebrae; Adult; Anesthetics, Local; Anesthesia, Epidural; Diskectomy, Percutaneous; Endoscopy; Spinal Nerve Roots; Dose-Response Relationship, Drug; Sensation; Aged
PubMed: 38915867
DOI: 10.2147/DDDT.S451980