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Redox Biology May 2024During cerebral ischemia-reperfusion conditions, the excessive reactive oxygen species in the ischemic penumbra region, resulting in neuronal oxidative stress,... (Review)
Review
During cerebral ischemia-reperfusion conditions, the excessive reactive oxygen species in the ischemic penumbra region, resulting in neuronal oxidative stress, constitute the main pathological mechanism behind ischemia-reperfusion damage. Swiftly reinstating blood perfusion in the ischemic penumbra zone and suppressing neuronal oxidative injury are key to effective treatment. Presently, antioxidants in clinical use suffer from low bioavailability, a singular mechanism of action, and substantial side effects, severely restricting their therapeutic impact and widespread clinical usage. Recently, nanomedicines, owing to their controllable size and shape and surface modifiability, have demonstrated good application potential in biomedicine, potentially breaking through the bottleneck in developing neuroprotective drugs for ischemic strokes. This manuscript intends to clarify the mechanisms of cerebral ischemia-reperfusion injury and provides a comprehensive review of the design and synthesis of antioxidant nanomedicines, their action mechanisms and applications in reversing neuronal oxidative damage, thus presenting novel approaches for ischemic stroke prevention and treatment.
PubMed: 38759419
DOI: 10.1016/j.redox.2024.103185 -
Medicine May 2024This study aims to investigate the effect of amantadine use on neurological outcomes and mortality in patients with severe traumatic brain injury (TBI) (Glasgow coma... (Observational Study)
Observational Study
This study aims to investigate the effect of amantadine use on neurological outcomes and mortality in patients with severe traumatic brain injury (TBI) (Glasgow coma score [GCS] between 3 and 8) who have been followed up on mechanical ventilators in the intensive care unit (ICU). Data from the hospital's electronic records were retrospectively searched. Patients over 18 years of age, with severe brain trauma (GCS between 3-8), who were treated with endotracheal intubation and invasive mechanical ventilation at admission to the ICU, and who were treated with Amantadine hydrochloride at least once in the first week of follow-up were included in the study. To evaluate the patients' neurological outcomes, the GCS and FOUR scores were used. GCS and FOUR scores were recorded on the 1st, 3rd, and 7th days of the first week. In addition, the score difference between the 1st and 7th day was calculated for both scores. The patients were divided into 2 groups: those receiving amantadine treatment (Group A, n = 44) and the control group (Group C, n = 47). The median age of all patients was 39 (18-81) (P = .425). When Group A and Group C were compared, no statistically significant results were found between the 1st, 3rd, and 7th day GCS values (P = .474, P = .483, and P = 329, respectively). However, the difference in GCS values between day 1 and day 7 (∆ GCS 7-1) was statistically significant (P = .012). Similarly, when Group A and Group C were compared, no statistically significant results were found between the 1st, 3rd, and 7th day FOUR score values (P = .948, P = .471, and P = .057, respectively). However, the FOUR score values between day 1 and day 7 (∆ FOUR score 7-1) were statistically significant (P = .004). There was no statistically significant difference among the groups in terms of ICU length of stay, duration of non-ICU hospital stay, and length of hospital stay (P = .222, P = .175, and P = .067, respectively). Amantadine hydrochloride may help improve neurological outcomes in patients with severe TBI. However, further research is needed to investigate this topic.
Topics: Humans; Amantadine; Respiration, Artificial; Male; Female; Middle Aged; Adult; Retrospective Studies; Intensive Care Units; Aged; Glasgow Coma Scale; Adolescent; Aged, 80 and over; Brain Injuries, Traumatic; Young Adult; Treatment Outcome; Craniocerebral Trauma
PubMed: 38758901
DOI: 10.1097/MD.0000000000038172 -
Medicine May 2024Paroxysmal sympathetic hyperexcitability (PSH) is a group of complex syndromes with various etiologies. Previous studies were limited to the description of traumatic...
BACKGROUND
Paroxysmal sympathetic hyperexcitability (PSH) is a group of complex syndromes with various etiologies. Previous studies were limited to the description of traumatic brain injury (TBI), and the description of PSH after other types of brain injury was rare. We explored the clinical features, treatment, and prognosis of PSH after various types of brain injuries.
METHODS
Patients admitted to the neurosurgery intensive care unit with PSH after brain injury from July 2019 to December 2022 were included. Demographic data, clinical manifestations, drug therapy, and disease prognosis were retrospectively collected and analyzed.
RESULTS
Fifteen male and 9 female patients with PSH after brain injury were selected. TBI was most likely to cause PSH (66.7%), followed by spontaneous intracerebral hemorrhage (25%). Glasgow coma scale scores of 19 patients (79.2%) were lower than 8 and 14 patients (58.3%) underwent tracheotomy. Electroencephalogram monitoring was performed in 12 individuals, none of which showed epileptic waves. Clinical symptom scale showed mild symptoms in 17 cases (70.8%). Almost all patients were administered a combination of drugs. After follow-up, most patients had a poor prognosis and 2 (8.3%) died after discharge.
CONCLUSION
The etiology of PSH is complex. TBI may be the most common cause of PSH. Non-TBI may also be an important cause of PSH. Therefore, early identification, prevention and diagnosis are helpful for determining the prognosis and outcome of the disease.
Topics: Humans; Male; Female; Middle Aged; Adult; Retrospective Studies; Prognosis; Electroencephalography; Glasgow Coma Scale; Brain Injuries; Aged; Autonomic Nervous System Diseases; Brain Injuries, Traumatic; Cerebral Hemorrhage
PubMed: 38758899
DOI: 10.1097/MD.0000000000035375 -
JAMA Network Open May 2024Providing assisted ventilation during delayed umbilical cord clamping may improve outcomes for extremely preterm infants. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Providing assisted ventilation during delayed umbilical cord clamping may improve outcomes for extremely preterm infants.
OBJECTIVE
To determine whether assisted ventilation in extremely preterm infants (23 0/7 to 28 6/7 weeks' gestational age [GA]) followed by cord clamping reduces intraventricular hemorrhage (IVH) or early death.
DESIGN, SETTING, AND PARTICIPANTS
This phase 3, 1:1, parallel-stratified randomized clinical trial conducted at 12 perinatal centers across the US and Canada from September 2, 2016, through February 21, 2023, assessed IVH and early death outcomes of extremely preterm infants randomized to receive 120 seconds of assisted ventilation followed by cord clamping vs delayed cord clamping for 30 to 60 seconds with ventilatory assistance afterward. Two analysis cohorts, not breathing well and breathing well, were specified a priori based on assessment of breathing 30 seconds after birth.
INTERVENTION
After birth, all infants received stimulation and suctioning if needed. From 30 to 120 seconds, infants randomized to the intervention received continuous positive airway pressure if breathing well or positive-pressure ventilation if not, with cord clamping at 120 seconds. Control infants received 30 to 60 seconds of delayed cord clamping followed by standard resuscitation.
MAIN OUTCOMES AND MEASURES
The primary outcome was any grade IVH on head ultrasonography or death before day 7. Interpretation by site radiologists was confirmed by independent radiologists, all masked to study group. To estimate the association between study group and outcome, data were analyzed using the stratified Cochran-Mantel-Haenszel test for relative risk (RR), with associations summarized by point estimates and 95% CIs.
RESULTS
Of 1110 women who consented to participate, 548 were randomized and delivered infants at GA less than 29 weeks. A total of 570 eligible infants were enrolled (median [IQR] GA, 26.6 [24.9-27.7] weeks; 297 male [52.1%]). Intraventricular hemorrhage or death occurred in 34.9% (97 of 278) of infants in the intervention group and 32.5% (95 of 292) in the control group (adjusted RR, 1.02; 95% CI, 0.81-1.27). In the prespecified not-breathing-well cohort (47.5% [271 of 570]; median [IQR] GA, 26.0 [24.7-27.4] weeks; 152 male [56.1%]), IVH or death occurred in 38.7% (58 of 150) of infants in the intervention group and 43.0% (52 of 121) in the control group (RR, 0.91; 95% CI, 0.68-1.21). There was no evidence of differences in death, severe brain injury, or major morbidities between the intervention and control groups in either breathing cohort.
CONCLUSIONS AND RELEVANCE
This study did not show that providing assisted ventilation before cord clamping in extremely preterm infants reduces IVH or early death. Additional study around the feasibility, safety, and efficacy of assisted ventilation before cord clamping may provide additional insight.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02742454.
Topics: Humans; Infant, Newborn; Infant, Extremely Premature; Female; Male; Umbilical Cord Clamping; Canada; Respiration, Artificial; Cerebral Intraventricular Hemorrhage; Umbilical Cord; Continuous Positive Airway Pressure; Gestational Age; Time Factors; United States
PubMed: 38758557
DOI: 10.1001/jamanetworkopen.2024.11140 -
International Journal of Tryptophan... 2024Stem cells are ubiquitously found in various tissues and organs in the body, and underpin the body's ability to repair itself following injury or disease initiation,... (Review)
Review
Stem cells are ubiquitously found in various tissues and organs in the body, and underpin the body's ability to repair itself following injury or disease initiation, though repair can sometimes be compromised. Understanding how stem cells are produced, and functional signaling systems between different niches is critical to understanding the potential use of stem cells in regenerative medicine. In this context, this review considers kynurenine pathway (KP) metabolism in multipotent adult progenitor cells, embryonic, haematopoietic, neural, cancer, cardiac and induced pluripotent stem cells, endothelial progenitor cells, and mesenchymal stromal cells. The KP is the major enzymatic pathway for sequentially catabolising the essential amino acid tryptophan (TRP), resulting in key metabolites including kynurenine, kynurenic acid, and quinolinic acid (QUIN). QUIN metabolism transitions into the adjoining de novo pathway for nicotinamide adenine dinucleotide (NAD) production, a critical cofactor in many fundamental cellular biochemical pathways. How stem cells uptake and utilise TRP varies between different species and stem cell types, because of their expression of transporters and responses to inflammatory cytokines. Several KP metabolites are physiologically active, with either beneficial or detrimental outcomes, and evidence of this is presented relating to several stem cell types, which is important as they may exert a significant impact on surrounding differentiated cells, particularly if they metabolise or secrete metabolites differently. Interferon-gamma (IFN-γ) in mesenchymal stromal cells, for instance, highly upregulates rate-limiting enzyme indoleamine-2,3-dioxygenase (IDO-1), initiating TRP depletion and production of metabolites including kynurenine/kynurenic acid, known agonists of the Aryl hydrocarbon receptor (AhR) transcription factor. AhR transcriptionally regulates an immunosuppressive phenotype, making them attractive for regenerative therapy. We also draw attention to important gaps in knowledge for future studies, which will underpin future application for stem cell-based cellular therapies or optimising drugs which can modulate the KP in innate stem cell populations, for disease treatment.
PubMed: 38757094
DOI: 10.1177/11786469241248287 -
Brain & Spine 2024It was not even a century ago when a spinal cord injury (SCI) would inevitably result in a fatal outcome, particularly for those with complete SCI. Throughout history,... (Review)
Review
INTRODUCTION
It was not even a century ago when a spinal cord injury (SCI) would inevitably result in a fatal outcome, particularly for those with complete SCI. Throughout history, there have been extensive endeavours to change the prospects for SCI patients by performing surgery, even though many believed that there was no way to alter the catastrophic course of SCI. To this day, the debate regarding the efficacy of surgery in improving the neurological outcome for SCI patients persists, along with discussions about the timing of surgical intervention.
RESEARCH QUESTION
How have the historical surgical results shaped our perspective on the surgical treatment of SCI?
MATERIAL AND METHODS
Narrative literature review.
RESULTS
Throughout history there have been multiple surgical attempts to alter the course of SCI, with conflicting results. While studies suggest a potential link between timing of surgery and neurological recovery, the exact impact of immediate surgery on individual cases remains ambiguous. It is becoming more evident that, alongside surgical intervention, factors specific to both the patient and their surgical treatment will significantly influence neurological recovery.
CONCLUSION
Although a growing number of studies indicates a potential correlation of surgical timing and neurological outcome, the precise influence of urgent surgery on an individual basis remains uncertain. It is increasingly apparent that, despite surgery, patient- and treatment-specific factors will also play a role in determining the neurological outcome. Notably, these very factors have influenced the results in previous studies and our views concerning surgical timing.
PubMed: 38756860
DOI: 10.1016/j.bas.2024.102825 -
Frontiers in Immunology 2024Intracerebral hemorrhage (ICH) often triggers oxidative stress through reactive oxygen species (ROS). Transforming growth factor-β-activated kinase 1 (TAK1) plays a...
INTRODUCTION
Intracerebral hemorrhage (ICH) often triggers oxidative stress through reactive oxygen species (ROS). Transforming growth factor-β-activated kinase 1 (TAK1) plays a pivotal role in regulating oxidative stress and inflammation across various diseases. 5Z-7-Oxozeaenol (OZ), a specific inhibitor of TAK1, has exhibited therapeutic effects in various conditions. However, the impact of OZ following ICH and its underlying molecular mechanisms remain elusive. This study aimed to explore the possible role of OZ in ICH and its underlying mechanisms by inhibiting oxidative stress-mediated pyroptosis.
METHODS
Adult male Sprague-Dawley rats were subjected to an ICH model, followed by treatment with OZ. Neurobehavioral function, blood-brain barrier integrity, neuronal pyroptosis, and oxidative stress markers were assessed using various techniques including behavioral tests, immunofluorescence staining, western blotting, transmission electron microscopy, and biochemical assays.
RESULTS
Our study revealed that OZ administration significantly inhibited phosphorylated TAK1 expression post-ICH. Furthermore, TAK1 blockade by OZ attenuated blood-brain barrier (BBB) disruption, neuroinflammation, and oxidative damage while enhancing neurobehavioral function. Mechanistically, OZ administration markedly reduced ROS production and oxidative stress by facilitating nuclear factor-erythroid 2-related factor 2 (NRF2) nuclear translocation. This was accompanied by a subsequent suppression of the NOD-like receptor protein 3 (NLRP3) activation-mediated inflammatory cascade and neuronal pyroptosis.
DISCUSSION
Our findings highlight that OZ alleviates brain injury and oxidative stress-mediated pyroptosis via the NRF2 pathway. Inhibition of TAK1 emerges as a promising approach for managing ICH.
Topics: Animals; Pyroptosis; NF-E2-Related Factor 2; Oxidative Stress; Cerebral Hemorrhage; Male; Rats; Signal Transduction; MAP Kinase Kinase Kinases; Rats, Sprague-Dawley; Neurons; Blood-Brain Barrier; Disease Models, Animal; Brain Injuries; Reactive Oxygen Species; Lactones; Resorcinols; Zearalenone
PubMed: 38756773
DOI: 10.3389/fimmu.2024.1386780 -
Frontiers in Cardiovascular Medicine 2024Human and animal studies have demonstrated the mechanisms and benefits of aerobic exercise for both cardiovascular and neurovascular health. Aerobic exercise induces... (Review)
Review
Human and animal studies have demonstrated the mechanisms and benefits of aerobic exercise for both cardiovascular and neurovascular health. Aerobic exercise induces neuroplasticity and neurophysiologic reorganization of brain networks, improves cerebral blood flow, and increases whole-body VO2 (peak oxygen consumption). The effectiveness of a structured cardiac rehabilitation (CR) program is well established and a vital part of the continuum of care for people with cardiovascular disease. Individuals post stroke exhibit decreased cardiovascular capacity which impacts their neurologic recovery and extends disability. Stroke survivors share the same risk factors as patients with cardiac disease and can therefore benefit significantly from a comprehensive CR program in addition to neurorehabilitation to address their cardiovascular health. The inclusion of individuals with stroke into a CR program, with appropriate adaptations, can significantly improve their cardiovascular health, promote functional recovery, and reduce future cardiovascular and cerebrovascular events thereby reducing the economic burden of stroke.
PubMed: 38756753
DOI: 10.3389/fcvm.2024.1376616 -
Heliyon May 2024The progression of liver diseases, from viral hepatitis and fatty liver disease to cirrhosis and hepatocellular carcinoma (HCC), is the most representative series of... (Review)
Review
The progression of liver diseases, from viral hepatitis and fatty liver disease to cirrhosis and hepatocellular carcinoma (HCC), is the most representative series of pathological events in liver diseases. While serotonin (5-HT) primarily regulates brain functions such as psychology, mood, and appetite in the central nervous system (CNS), peripheral 5-HT plays a crucial role in regulating tumor development, glucose and lipid metabolism, immune function and inflammatory response related to liver diseases. These peripheral physiological processes involving 5-HT are the key mechanisms driving the development of these liver diseases. This study presents an overview of the existing literature, focusing on the role of 5-HT in HCC, cirrhosis, fatty liver disease, viral hepatitis, and liver injury. In summary, while 5-HT promotes liver regeneration, it can also contribute to the progression of chronic liver disease. These findings indicate the potential for the development and use of 5-HT-related drugs for the treatment of liver diseases, including HCC and cirrhosis.
PubMed: 38756588
DOI: 10.1016/j.heliyon.2024.e30703 -
Frontiers in Neuroscience 2024
PubMed: 38756410
DOI: 10.3389/fnins.2024.1413483