Cerebral Hypoperfusion Research Articles

Abnormal local cortical functional connectivity due to interneuron dysmaturation after neonatal intermittent hypoxia.

Prematurely born infants often experience frequent hypoxic episodes due to immaturity of respiratory control resulting in disturbances of cortical development and long-term cognitive and behavioral abnormalities. We hypothesize that neonatal intermittent hypoxia alters maturation of cortical excitatory and inhibitory circuits that can be detected early with functional MRI. C57BL/6 mouse male and female pups were exposed to an intermittent hypoxia (IH) regimen from P3 to P7, corresponding to pre-term humans. Adult mice after neonatal IH exhibited motor hyperactivity and impaired motor learning in complex wheel tests. Patch clamp and evoked field potential recordings revealed increased glutamatergic synaptic transmission. To investigate the role of GABAergic inhibition on glutamatergic transmission during the developmental, we applied a selective GABAA receptor inhibitor picrotoxin. A decreased synaptic inhibitory drive in the motor cortex was evidenced by miniature IPSC frequency on pyramidal cells, multi-unit activity recording in vivo with picrotoxin injection, and decreased interneuron density. There was also an increased tonic depolarizing effect of picrotoxin after IH on Betz cells' membrane potential on patch clamp and direct current potential in extracellular recordings. The amplitude of low-frequency fluctuation on resting-state fMRI was larger, with a larger increase in regional homogeneity index after picrotoxin injection in the IH group.The increased glutamatergic transmission, decreased numbers, and activity of inhibitory interneurons after neonatal IH may affect the maturation of connectivity in cortical networks, resulting in long-term cognitive and behavioral changes. Functional MRI reveals increased intrinsic connectivity in the sensorimotor cortex, suggesting neuronal dysfunction in cortical maturation after neonatal IH.Significance Statement The study demonstrates that perinatal hypoxic brain injury disrupts the balance between excitatory and inhibitory neurotransmission in developing cortical networks. This disruption, potentially caused by functional deficiencies in GABAergic interneurons alongside increased glutamatergic transmission, may contribute to altered brain connectivity and the observed behavioral deficits, including hyperactivity and cognitive difficulties. This research provides insights into how perinatal brain injury disrupts the balance of neural excitation and inhibition, which can be detected as altered local resting-state fMRI connectivity. These findings contribute to our understanding of possible cellular underpinning of clinical fMRI findings after perinatal brain injury.

Ultra-Low-Field Portable Brain Magnetic Resonance Imaging in Patients With Cardiac Devices: Current Evidence and Future Directions.

The use of cardiac devices, including mechanical circulatory support (MCS), cardiac implantable electronic devices (CIEDs), and pacing wires, has increased and significantly improved survival in patients with severe cardiac failure. However, these devices are frequently associated with acute brain injuries (ABIs) including ischemic strokes, intracranial hemorrhages, seizures, and hypoxic-ischemic brain injury which contribute substantially to morbidity and mortality. Computed tomography (CT) and magnetic resonance imaging (MRI), the standard imaging modalities for ABI diagnosis, can pose significant challenges in this patient population due to the risks associated with patient transportation and the incompatibility of ferromagnetic components of certain cardiac devices with high magnetic field of the MRI. This review discusses the application of Ultralow-field portable MRI (ULF-pMRI), which operates at much lower magnetic field (0.064 T), with the potential to allow safe bedside imaging of critically ill patients. In this review, we detail the clinical studies and research findings defining the safety, feasibility, and diagnostic utility of ULF-pMRI in detecting ABI in the critically ill. We further discuss the potential broader applications of ULF-pMRI, as a standard diagnostic tool for neurocritical care in patients with cardiac devices. The integration of such technology into current practice promises to enhance diagnostic accuracy, improve patient outcomes, and optimize healthcare resources.

Melatonin Mitigates Acidosis-Induced Neuronal Damage by Up-Regulating Autophagy via the Transcription Factor EB

Acidosis, a common feature of cerebral ischemia and hypoxia, results in neuronal damage and death. This study aimed to investigate the protective effects and mechanisms of action of melatonin against acidosis-induced neuronal damage. SH-SY5Y cells were exposed to an acidic environment to simulate acidosis, and a photothrombotic (PT) infarction model was used to establish an animal model of cerebral ischemia of male C57/BL6J mice. Both in vivo and in vitro studies demonstrated that acidosis increased cytoplasmic transcription factor EB (TFEB) levels, reduced nuclear TFEB levels, and suppressed autophagy, as evidenced by elevated p62 levels, a higher LC3-II/LC3-I ratio, decreased synapse-associated proteins (PSD-95 and synaptophysin), and increased neuronal apoptosis. In contrast, melatonin promoted the nuclear translocation of TFEB, enhanced autophagy, and reversed neuronal apoptosis. Moreover, the role of TFEB in melatonin’s neuroprotective effects was validated by modulating TFEB nuclear translocation. In conclusion, melatonin mitigates acidosis-induced neuronal damage by promoting the nuclear translocation of TFEB, thereby enhancing autophagy. These findings offer new insights into potential treatments for acidosis.

Effects of intrathecal administration of sodium nitroprusside and nicardipine on cerebral pial microcirculation, cortical tissue oxygenation, and electrocortical activity in the early post-resuscitation period in a porcine cardiac arrest model.

Recent studies suggested intrathecal vasodilator administration as a therapy to mitigate post-ischemic cerebral hypoperfusion following cardiac arrest. We examined the effects of two commonly used intrathecal vasodilators, sodium nitroprusside (SNP) and nicardipine, on cerebral pial microcirculation, cortical tissue oxygen tension (PctO2), and electrocortical activity in the early post-resuscitation period using a porcine model of cardiac arrest. Thirty pigs were resuscitated after 14 min of untreated cardiac arrest. At 30 min after resuscitation from cardiac arrest, 30 pigs randomly received 4 mg of SNP, 4 mg of nicardipine, or saline placebo via subdural intracranial catheters and were observed for 5 h. Group effect and group-time interaction were assessed using linear mixed-effects models. The mean arterial pressure was lower in the nicardipine group (coefficient [95% confidence interval {CI}], -15.824 [-24.082 to -7.566]) and higher in the SNP group (coefficient [95%CI], 11.232 [2.974-19.490]) compared to the saline group. The percentage of pial arteriole diameter relative to the pre-arrest baseline value (coefficient [95% CI], 48.970 [13.884-84.057]), microvascular flow index (coefficient [95% CI], 0.296 [0.071-0.521]), and PctO2 (coefficient [95% CI], 26.926 [12.404-41.449]) were higher in the SNP group but not in the nicardipine group compared to the saline group. Amplitude-integrated electroencephalography amplitude recovery was faster in the SNP group (coefficient [95% CI], 1.149 [0.468-1.829]) but not in the nicardipine group compared to the saline group. In conclusion, intrathecal SNP but not nicardipine was effective in treating post-ischemic cerebral hypoperfusion after cardiac arrest.

Effects of Resuscitation and Simulation Team Training on the Outcome of Neonates with Hypoxic-Ischemic Encephalopathy in South Tyrol

Background/Objectives: Neonatal hypoxic-ischemic encephalopathy (HIE) due to perinatal complications remains an important pathology with a significant burden for neonates, families, and the healthcare system. Resuscitation and simulation team training are key elements in increasing patient safety. In this retrospective cohort study, we evaluated whether regular constant training of all personnel working in delivery rooms in South Tyrol improved the outcome of neonates with HIE. Methods: We retrospectively analyzed three groups of neonates with moderate to severe HIE who required therapeutic hypothermia. The first group included infants born before the systematic introduction of training and was compared to the second group, which included infants born after three years of regular training. A third group, which included infants born after the SARS-CoV-2 pandemic, was compared with the previous two to evaluate retention of skills and the long-term effect of our training program. Results: Over the three study periods, mortality decreased from 41.2% to 0% and 14.3%, respectively. There was also a significant reduction of patients with subclincal seizures detected only through EEG, from 47.1% in the first period to 43.7% and 14.3% in the second and third study periods, respectively. Clinical manifestations of seizures decreased significantly from 47.1% to 37.5% and 10.7%, respectively, as well as severe brain lesions in ultrasound (US) and MRI. Conclusions: In this study, constant and regular simulation training for all birth attendants significantly decreases mortality and improves the outcome in neonates with moderate to severe HIE. This positive effect seems to last even after a one-year period during which training sessions could not be performed due to the COVID-19 pandemic.

Novel brain SPECT imaging unravels abnormal cerebral perfusion in patients with postural orthostatic tachycardia syndrome and cognitive dysfunction

Cognitive dysfunction is frequently reported in individuals with postural orthostatic tachycardia syndrome (POTS), possibly resulting from reduced cerebral blood flow (CBF). We used brain SPECT, an accessible imaging modality that has not been systematically evaluated in this patient group. Retrospective review of participants from our registry was undertaken to identify those who had a brain SPECT performed for investigation of cognitive dysfunction. Abnormal CBF was taken as z-score > 2 standard deviations of healthy control reference values. Patient reported outcome measures (PROMs) such as autonomic, gastric and quality of life symptom scores were analyzed. From a total of 56 participants (mean 34.8 ± 10.7 years, 88% females), PROMs indicate: moderate to severe autonomic dysfunction in 75%; at least mild to moderate gastroparesis in 23%; low global health rating and utility scores. Abnormal CBF was seen in 61% but did not differ by POTS triggers. The regions with the lowest mean z-scores were the lateral prefrontal and sensorimotor cortices. Hierarchal regression analyses found number of brain regions with abnormal CBF, autonomic and gastric symptoms to account for 51% of variances in health utility. Cerebral hypoperfusion is prevalent in those with POTS and cognitive dysfunction even whilst supine, contributing to reduced quality of life.

Toll-Like Receptor 4-Mediated Neuroinflammation: Updates on Pathological Roles and Therapeutic Strategies in Chronic Cerebral Hypoperfusion.

Neuroinflammation has been acknowledged as being one of the main pathologies that occur following chronic cerebral hypoperfusion (CCH). Since it significantly contributes to neuronal cell damage and thereby leads to cognitive impairment, the signals related to inflammation in hypoperfusion injury have been extensively investigated over the past few years. Toll-like receptor 4 (TLR4) is the key receptor responsible for immune and inflammatory reactions. It has been reported that TLR4 is involved in the pathology of several diseases and has emerged as a therapeutic target for developing a variety of anti-inflammatory compounds. This study explored the pathological roles of TLR4 that potentially cause the promotion of neuroinflammation in CCH damage. The evidence pertinent to the activation of TLR4 and its downstream inflammatory cascades following CCH are also summarized. This study also demonstrated the therapeutic potential of TLR4 inhibition, whether through drugs, substances, or other treatment strategies, in models of CCH-induced neurological dysfunction. The limitations of the accumulated evidence are addressed and discussed in this study. A deeper understanding of the roles of TLR4 in neuroinflammation following CCH damage may help inform the machinery behind pathological processes for advancing further neuroscientific research and developing therapeutic strategies for vascular dementia.

Inpatient care of sick newborns in special new born care units in Odisha

Background: Inpatient care assessment of sick newborns in Special New Born Care Units (SNCUs) in Odisha is vital for feedback and improvement. This study aimed to characterize the quality of care provided by SNCUs in selected districts in Odisha during 2020-2022. Methods: Using secondary data from 10 SNCUs of District Hospitals in Odisha over a three-year period (2020–2022), we performed a cross-sectional descriptive analysis on all admitted neonates. Age, gender, birth weight, admission indication, maturity, mortality profile, referral, and admission pattern were all profiled. Excel 2021 was used to extract the data, and Excel and Epi Info were used for analysis. Results: Of the 50226 babies admitted to SNCUs, 24383 (48.5%) were inborn. Males made- up 58.4% of the infants. 995 babies (2.0%) weighed less than 1000 grams, while 58.5% of neonates had low birth weights (less than 2500 grams). Prematurity (n=4363, 8.7%), low birth weight (n=6757, 13.5%), refusal to feed (n=5327, 10.6%), neonatal jaundice (n=9616, 19.1%), and perinatal asphyxia (n=14421) account for 28.7% of hospitalizations. Of the total, 4.1% left the SNCU against medical advice, 9.7% died, 11.3% were referred, and 74.8% were discharged. The leading causes of death were preterm birth, infection, hypoxic-ischemic-encephalopathy (HIE), and birth asphyxia. The Composite SQCI performs satisfactorily (0.60-0.66) over the course of the twelve quarters Conclusion: Birth asphyxia is the primary cause of illness and mortality in neonates. Early referrals, effective intervention, and excellent prenatal care are essential to prevent it.

Research hotspots and trends in the application of electroencephalography for assessment of disorders of consciousness: a bibliometric analysis

ObjectiveDisorders of consciousness (DoC) result from severe traumatic brain injury and hypoxia or ischemia of brain tissues, leading to impaired perceptual abilities. Electroencephalography (EEG) is a non-invasive and widely applicable technology used for assessing DoC. We aimed to identify the research hotspots in this field through a systematic analysis.MethodsRelevant studies published from January 1, 2004 to December 31, 2023 were retrieved from the Web of Science Core Collection database. The data were analyzed and visualized using CiteSpace, VOSviewer, and SCImago Graphica.ResultsIn total, 1,639 relevant publications were retrieved. The country with the highest number of publications was the United States, the most productive institution was Harvard University, the journal with the highest output was Clinical Neurophysiology, and the journal with the highest total number of citations was Neurology. The author with the most publications was Steven Laureys and the most common keyword was “vegetative state.”ConclusionThe field is undergoing rapid development, characterized by a proliferation of advanced technologies and an increased emphasis on international collaboration. The document offers an impartial perspective on the advancements of the research study for the benefit of the researchers.

Changes in the treatment and outcomes of different severities of neonatal hypoxic ischemic encephalopathy in California: a retrospective cohort study.

Evaluate the changes in management and outcomes of Californian infants with hypoxic ischemic encephalopathy (HIE). Infants with HIE were identified from a California administrative birth cohort using ICD codes and divided into two epochs, Epoch 1 (2010-2015) and Epoch 2 (2016-2019). Risk ratios (RR) for induced hypothermia (IH) in each epoch and their outcomes were calculated using log-linear regression. In this cohort, 4779 infants with HIE were identified. Incidence of HIE in California increased yearly from 0.5/1000 California births to a peak of 1.5/1000 births in 2018. The use of IH in infants with mild HIE increased in Epoch 2 compared to Epoch 1. There was no significant difference in outcomes between epochs for infants with mild HIE that received IH including no difference in neonatal seizures. Significantly more infants with mild HIE received IH since 2015 in California, but no significant difference in outcomes.

Integrated analysis of chromatin and transcriptomic profiling of the striatum after cerebral hypoperfusion in mice

BackgroundVascular cognitive impairment (VCI) is a significant contributor to dementia, yet the precise mechanisms underlying the cognitive decline associated with chronic cerebral hypoperfusion (CCH) remain unclear. This study investigated the molecular and epigenetic changes in the striatum, a brain region critical for motor function and cognition, following chronic hypoperfusion using a bilateral common carotid artery stenosis (BCAS) model in mice.MethodsRNA-seq was utilized to identify differentially expressed genes (DEGs) associated with hypoperfusion. In parallel, ATAC-seq was used to assess changes in chromatin accessibility within the striatum, providing insight into the epigenome and potential regulatory mechanisms. The integration of these datasets allowed us to correlate chromatin accessibility with transcriptional activity and to identify key transcription factors driving the observed gene expression changes.ResultsAnalysis of striatum-specific transcriptome revealed significant upregulation of immune response genes, particularly type II interferon signaling, and downregulation of neural activation pathways. Analysis of striatum-specific epigenome showed increased chromatin accessibility at promoters of immune-related genes. Integrated analysis highlighted PU.1 as a key transcription factor in upregulated pathways, while neural pathways lacked epigenetic regulation, revealing distinct molecular responses in the striatum following chronic hypoperfusion.ConclusionsOur findings indicate that upregulated pathways in the striatum following BCAS-induced CCH are driven by epigenetic changes, while downregulated pathways occur independently of these modifications. Additionally, PU.1 plays a critical role in mediating immune responses, offering a potential target for therapeutic intervention.

Cardiovascular Performance in Neonates with Hypoxic-Ischemic Encephalopathy Under Therapeutic Hypothermia: Evaluation by Conventional and Advanced Echocardiographic Techniques.

This study aimed to evaluate the hemodynamic and ventricular performance of neonates with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia using conventional and advanced echocardiographic techniques. This observational, prospective study included 22 neonates with HIE matched with 22 healthy neonates. Echocardiographic studies were performed 24h after achieving target temperature during hypothermia and 24h after rewarming. Evaluated echocardiographic parameters included ejection fraction (EF), shortening fraction (SF), right ventricular fractional area change, biventricular Tei index, right ventricular s' wave velocity, tricuspid annular plane systolic excursion, biventricular stroke volume and cardiac output, left ventricular (LV) and right ventricular (RV) global longitudinal strain (GLS), LV circumferential and radial strain, LV twist, and LV torsion. LV EF and SF did not change significantly between the hypothermia and rewarming periods (EF:73 ± 7% vs. 74 ± 5%, p = 0.21; SF:39 ± 6% vs. 41 ± 5%, p = 0.26); however, both were higher after rewarming compared to the control group (EF:70 ± 5%, p = 0.003; SF:36 ± 4%, p = 0.002). There were no significant differences in LV GLS, circumferential and radial strain, twist, and torsion between the HIE and control groups. Pulmonary artery systolic pressure (PASP) and RVGLS were worse in the study group compared to the control group (PASP: hypothermia 45 ± 24mmHg, p = 0.01; rewarming 53 ± 34mmHg, p = 0.01; control group 29 ± 11mmHg; RV GLS: hypothermia 18 ± 5%, p = 0.02; rewarming: 18 ± 4%, p = 0.01; control group 21 ± 2%). Therapeutic hypothermia appears to have no detrimental impact on LV systolic function. RV GLS was the only parameter that demonstrated impaired RV systolic function during therapeutic hypothermia, likely due to elevated PASP.

Data Collection Variability Across Neonatal Hypoxic-Ischemic Encephalopathy Registries.

To assess variability among data elements collected among existing neonatal hypoxic-ischemic encephalopathy (HIE) data registries worldwide and to determine the need for future harmonization of standard common data elements. This was a cross-sectional study of data elements collected from current or recently employed HIE registry data forms. Registries were identified by literature search and email inquiries to investigators worldwide. Data elements were categorized by group consensus. A total of 1,281 data elements were abstracted from 22 registries based in 14 countries, including 3 middle-income countries. Registries had a median of 106.5 distinct data elements per registry (range 59-458). The most commonly collected data were related to pregnancy, therapeutic hypothermia, and short-term hospital outcomes. The least consistently collected data were laboratory values other than acid/base status values. Only 4 variables were consistently collected in every registry. Five registries included neurodevelopmental follow-up fields and 5 others linked their data to a separate follow-up registry. Many HIE registries are collecting patient data around the world, but there is considerable variability in the number, type, and format of data collected. Future attempts to develop standard common data elements to harmonize data collection globally will be crucial to facilitate worldwide collaboration and to optimize management and outcome of neonatal HIE.

Comparison of Temporal Artery and Rectal Temperature Measurement During Cooling and Rewarming in Neonates Treated for Hypoxic Ischemic Encephalopathy.

Finding an accurate and simple method of thermometry in the neonatal intensive care unit is important. The temporal artery thermometer (TAT) has been recommended for all ages by the manufacturer; however, there is insufficient evidence for the use of TAT in infants, especially to detect hypothermia. To assess the accuracy of the TAT in hypothermic neonates in comparison to a rectal thermometer. This study was a naturalistic, quantitative, and observational study. Temporal artery temperatures (using Exergen TemporalScanner 5000) were compared to rectal temperatures in critically ill infants in the neonatal intensive care unit undergoing therapeutic hypothermia for hypoxic ischemic encephalopathy. Temperatures were taken during a 72-hour cooling period at 33.5°C and a 6-hour rewarming period to normothermia of 36.5°C. Nineteen patients and 1280 temperature measurements were included in this study. During the cooling period, TAT and rectal temperatures had a weak correlation (r=0.34, P <.001). The correlation during the rewarming period was much stronger (r=0.70, P <.001), indicating less variability in measures, but not agreement. On average, regardless of period, the TAT temperatures read 0.43°C (95% confidence interval, 0.37-0.49, P <.001) warmer than the rectal temperatures. The cooling or warming period had no effect on this difference between temperatures. This study found that temperatures obtained with a TAT are generally warmer than the accepted standard core rectal temperature in hypothermic neonates, and we do not recommend its use in critically ill neonates who require accurate temperature readings.

Accidental Autoerotic Deaths and Mental Disorder: A Scoping Review.

Accidental autoerotic death, more commonly known as "autoerotic asphyxia," is an extreme paraphilic behavior wherein individuals induce cerebral hypoxia during self-stimulated sexual activities, often by constricting the neck or obstructing respiratory passages. Data on accidental deaths caused by autoerotic play is very low because of the non-disclosure of the mode/circumstances of death or non-paralleled forensic systems in many countries. There is a high likelihood of coexisting mental disorders with such behavior. This review identifies the association of any comorbid mental disorder with accidental autoerotic deaths. On August 23, 2023, a systematic literature search was carried out through Cochrane, PubMed, ScienceDirect, and SCOPUS, and studies identified in the English language were screened using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Review (PRISMA-ScR) guideline. Eighteen studies identified specific mental disorders with autoerotic deaths, including paraphilia, vaginismus, gender dysphoria, multiplex paraphilia, alcohol dependence, bipolar disorder, borderline personality disorder, and substance use disorder. Inhalant use like chloroform, toluene, and xylene was implicated during autoerotic fantasies. Prospective clinical screening and comprehensive multicentric psychological autopsy studies are needed to clarify the prevalence of accidental autoerotic death and related mental health conditions in the future. Given the possibility of accidental death, it remains to be seen whether paraphilia involving a single harmful event could be classified as a specifier within the impulsive-compulsive-reward spectrum, similar to how newer diagnostic systems address substance use disorders.

Extracorporeal organ support as a bridging strategy to enable organ donation-acase report with literature review

We report the case of ayoung patient with severe hypoxic brain injury after cardiopulmonary resuscitation, resulting in brain death/death by neurologic criteria (BD/DNC). Consistent with the patient's expressed wishes, treatment was sustained to facilitate organ donation. However, in the context of asevere post-resuscitation syndrome and physiological disturbances resulting from BD/DNC, refractory circulatory shock ensued. Stabilization was only possible by mechanical circulatory support (MCS). By implementation of MCS for extracorporeal organ support (ECOS), successful organ donation was rendered possible. Further debate is required concerning ethical issues, particularly concerning resource distribution, the timing of ECOS in relation to the diagnosis of BD/DNC and concerning specific consent for the invasive procedure. Until guidelines are presented, we believe that ECOS should be considered in the management of select potential donors in severe shock even before, and certainly after the diagnosis of BD/DNC.

Intranasal Administrations of AP39-Loaded Liposomes Selectively Deliver H2S to Neuronal Mitochondria to Protect Neonatal Hypoxia-Ischemia by Targeting ERK1/2 and Caspase-1.

Mitochondrial dysfunction contributes to the pathology of hypoxia-ischemia (HI) brain damage by aberrant production of ROS. Hydrogen sulfide (H2S) has been demonstrated to exert neuroprotective effects through antioxidant mechanisms. However, the diffusion of H2S in vivo is not specifically targeted and may even be systemically toxic. In this study, based on mitochondria-targeted H2S donor AP39, we fabricated liposomes encapsulating AP39 (AP39@Lip) via intranasal delivery to improve functional recovery after HI brain injury. This study presents that intranasal administration of AP39@Lip was capable of attenuating acute brain injury by inhibiting mitochondrial dysfunction, apoptosis, neuroinflammation, and ROS production in the lesional cortex 3 days after HI brain injury. Similarly, AP39@Lip was observed to restore both short- and long-term function following HI injury without obvious toxicity. Mechanistically, the therapeutic effects of AP39@Lip mainly relied on its colocalization with neuronal mitochondria 24 h after administration and reversed H2S levels in the lesional cortex. Moreover, molecular docking and cellular thermal shift assay suggest that AP39 inhibited the activation of ERK1/2 and caspase-1 by directly binding to ERK1/2 or caspase-1. These results indicate that intranasal administration of AP39@Lip selectively delivered H2S to neuronal mitochondria and mitigated mitochondrial damage following HI insult by targeting ERK1/2 and caspase-1.

The Role of Proton Magnetic Resonance Spectroscopy in Neonatal and Fetal Brain Research.

The biochemical composition and structure of the brain are in a rapid change during the exuberant stage of fetal and neonatal development. 1H-MRS is a noninvasive tool that can evaluate brain metabolites in healthy fetuses and infants as well as those with neurological diseases. This review aims to provide readers with an understanding of 1) the basic principles and technical considerations relevant to 1H-MRS in the fetal-neonatal brain and 2) the role of 1H-MRS in early fetal-neonatal development brain research. We performed a PubMed search to identify original studies using 1H-MRS in neonates and fetuses to establish the clinical applications of 1H-MRS. The eligible studies for this review included original research with 1H-MRS applications to the fetal-neonatal brain in healthy and high-risk conditions. We ran our search between 2000 and 2023, then added in several high-impact landmark publications from the 1990s. A total of 366 results appeared. After, we excluded original studies that did not include fetuses or neonates, non-proton MRS and non-neurological studies. Eventually, 110 studies were included in this literature review. Overall, the function of 1H-MRS in healthy fetal-neonatal brain studies focuses on measuring the change of metabolite concentrations during neurodevelopment and the physical properties of the metabolites such as T1/T2 relaxation times. For high-risk neonates, studies in very low birth weight preterm infants and full-term neonates with hypoxic-ischemic encephalopathy, along with examining the associations between brain biochemistry and cognitive neurodevelopment are most common. Additional high-risk conditions included infants with congenital heart disease or metabolic diseases, as well as fetuses of pregnant women with hypertensive disorders were of specific interest to researchers using 1H-MRS. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

An open window: the crucial role of the gut-brain axis in neurodevelopmental outcomes post-neurocritical illness.

Among patients admitted to the pediatric intensive care unit, approximately 10% are discharged with a new functional morbidity. For those who were admitted with a neurocritical illness, the number can be as high as 60%. The most common diagnoses for a neurocritical illness admission include traumatic brain injury, status epilepticus, post-cardiac arrest, hypoxic ischemic encephalopathy, meningo/encephalitis, and stroke. The gut-brain axis is crucial to childhood development, particularly neurodevelopment. Alterations on either side of the bidirectional communication of the gut-brain axis have been shown to alter typical development and have been associated with autism spectrum disorder, anxiety, sleep disturbances, and learning disabilities, among others. For those patients who have experienced a direct neurologic insult, subsequent interventions may contribute to dysbiosis, which could compound injury to the brain. Increasing data suggests the existence of a critical window for both gut microbiome plasticity and neurodevelopment in which interventions could help or could harm and warrant further investigation.

Plasma Endothelin-1 Levels: Non-Predictors of Alzheimer's Disease Reveal Age Correlation in African American Women.

Background/Objectives: Alzheimer's disease (AD) and related dementias (ADRD) disproportionately impact racial and ethnic minorities. Contributing biological factors that explain this disparity have been elusive. Moreover, non-invasive biomarkers for early detection of AD are needed. Endothelin-1 (ET-1), a vasoconstrictive factor linked to cerebral vascular disease pathology and neuronal injury, could provide insights to better understand racial disparities in AD. As a potent vasoconstrictive peptide that regulates contractions in smooth muscle, endothelial cells, and pericytes, ET-1 may result in cerebral vascular constriction, leading to cerebral hypoperfusion; over time, this may result in neuronal injury, contributing to the pathology of AD. The role of the ET-1 system as a driver of ethnic disparities in AD requires further investigation. In the United States (U.S.), ET-1 dysregulation in Hispanic/Latinx (H/L) ethnic populations has largely been unexplored. Genetics linking ET-1 dysregulation and racial disparities in AD also require further investigation. In this study, we examined the role of the ET-1 protein in human plasma as a potential biomarker with predictive value for correlating with the development of AD by age, race, and sex. Methods: We examined ET-1 protein levels using quantitative mass spectrometry in AA and NHW patients with AD, along with controls. Results: A partial correlation between age at draw and ET-1, stratified by race and sex, while controlling for AD status, was significant for female AAs (r = 0.385, p = 0.016). When the data were not stratified but controlled for AD status, the partial correlation between age at draw and ET-1 was not significant (r = 0.108, p = 0.259). Conclusions: Based on the small number of plasma specimens and no plasma specimens from H/L individuals with AD, we conclude that ET-1 was clearly not a significant factor in predicting AD in this study and will require a larger scale study for validation.