Long-term Neurological Sequelae Research Articles

Neuroprotective effects of miRNA-326 knockout in neonatal hypoxic–ischemic brain damage mice via the δ-opioid receptor

Hypoxic–ischemic brain damage (HIBD) in the perinatal period is an important cause of cerebral damage and long-term neurological sequelae, and can place much pressure on families and society. Our previous study demonstrated that miRNA-326 reduces neuronal apoptosis by up-regulating the δ-opioid receptor (DOR) under oxygen–glucose deprivation in vitro. In the present study, we aimed to explore the neuroprotective effects of the miRNA-326/DOR axis by inhibiting apoptosis in HIBD using neonatal miRNA-326 knockout mice. Neonatal C57BL/6 mice, neonatal miRNA-326 knockout mice, and neonatal miRNA-326 knockout mice intraperitoneally injected with the DOR inhibitor naltrindole were treated with hypoxic-ischemia (HI). Neurological deficit scores, magnetic resonance imaging, terminal deoxynucleotidyl transferase-mediated uridine 5′-triphosphate-biotin nick end labeling, and Caspase-3, Bax, and B-cell lymphoma 2 (Bcl-2) expression were evaluated on day 2 after HI. Neurobehavioral analyses were performed on days 2 and 28 after HI. Additionally, the Morris water maze test was conducted on days 28. Compared with HI-treated neonatal C57BL/6 mice, HI-treated neonatal miRNA-326 knockout mice had higher neurological deficit scores, smaller cerebral infarction areas, and improved motor function, reaction ability, and long-term spatial learning and memory. These effects were likely the result of inhibiting apoptosis; the DOR inhibitor reversed these neuroprotective effects. Our findings indicate that miRNA-326 knockout plays a neuroprotective effect in neonatal HIBD by inhibiting apoptosis via the target gene DOR.

Time to full enteral feeding and its predictors among very low birth weight (VLBW) neonates admitted to the neonatal intensive care units (NICU) in comprehensive specialized hospitals in Northwest Ethiopia

BackgroundTime to full enteral feeding is the time when neonates start to receive all of their prescribed nutrition as milk feeds. Delayed to achieve full enteral feeding had resulted in short- and long-term physical and neurological sequelae. However, there are limited studies to assess the time to full enteral feeding and its predictors among very low birth-weight neonates in Ethiopia. Therefore, this study aimed to assess the time to full enteral feeding and its predictors among very low birth-weight neonates admitted to comprehensive specialized hospitals in Northwest Ethiopia.MethodsA multi-center institutional-based retrospective follow-up study was conducted among 409 VLBW neonates from March 1, 2019 to February 30, 2023. A simple random sampling method was used to select study participants. Data were entered into EpiData version 4.2 and then exported into STATA version 16 for analysis. The Kaplan–Meier survival curve together with the log-rank test was fitted to test for the presence of differences among groups. Proportional hazard assumptions were checked using a global test. Variables having a p- value < 0.25 in the bivariable Cox-proportional hazard model were candidates for multivariable analysis. An adjusted Hazard Ratio (AHR) with 95% Confidence Intervals (CI) was computed to report the strength of association, and variables having a P-value < 0.05 at the 95% confidence interval were considered statistically significant predictor variables.ResultThe median time to full enteral feeding was 10 (CI: 10–11) days. Very Low Birth-Weight (VLBW) neonates who received a formula feeding (AHR: 0.71, 95% CI: 0.53, 0.96), gestational age of 32–37 weeks (AHR: 1.66, 95% CI: 1.23, 2.23), without Necrotizing Enterocolitis (NEC) (AHR: 2.16, 95% CI: 1.65, 2.84), and single birth outcome (AHR: 1.42, 95% CI: 1.07, 1.88) were statistically significant variables with time to full enteral feeding.Conclusion and recommendationsThis study found that the median time to full enteral feeding was high. Type of feeding, Necrotizing Enterocolitis (NEC), Gestational Age (GA) at birth, and birth outcome were predictor variables. Special attention and follow-up are needed for those VLBW neonates with NEC, had a GA of less than 32 weeks, and had multiple birth outcomes.

Evaluation and outcome of hearing in meningitis patients

Background: Meningitis remains the most common cause of acquired severe to profound SNHL in childhood. Likewise, deafness is the most common long-term neurological sequelae of the disease. Important consideration following meningitis is the development of labyrinthitis ossificans in which there is new bone formation within the lumen of the otic capsule. Ossification of the labyrinth can develop within a few days of meningitis which can make cochlear implantation difficult. Every newborn should be promptly screened for any hearing deficit along with the patients having meningitis. The most easily available investigation are OAE and BERA. Methods: Our ambispective study of 25 patients was undertaken in a duration of 2 years in ENT department of civil hospital, Ahmedabad. All the patients underwent a detailed clinical examination and all routine audiological, and radiological investigations. Results: The prevalence of hearing loss in post meningitis pediatric age group is 40%. Females are affected more than males. Median age group of presentation with hearing deficit is 4 years. Patients with complete immunization history have lower incidence of hearing loss associated with meningitis than incomplete immunization. Ossification of the cochlea can develop as early as 6 days from the development of first symptom. Conclusions: Ossification of the cochlea can develop as early as 6 days from the development of first symptom. These are the candidates who should be prioritized for cochlear implant surgery. Patients with mild hearing loss recovered completely whereas those with profound hearing loss underwent cochlear implant surgery and were benefited with it.

Volumetric apparent diffusion coefficient histogram analysis in term neonatal asphyxia treated with hypothermia.

Our aim is to estimate the long-term neurological sequelae and prognosis in term neonatal asphyxia treated with hypothermia via volumetric apparent diffusion coefficient (ADC) map histogram analysis (HA). Brain MRI studies of 83 term neonates with asphyxia who received whole-body hypothermia treatment and examined between postnatal (PN) fourth and sixth days were retrospectively re-evaluated by 2 radiologists. Volumetric HA was performed for the areas frequently affected in deep and superficial asphyxia (thalamus, lentiform nucleus, posterior limb of internal capsule, corpus callosum forceps major, and perirolandic cortex-subcortical white matter) on ADC map. The quantitative ADC values were obtained separately for each region. Qualitative-visual (conventional) MRI findings were also re-evaluated. Neonates were examined neurodevelopmentally according to the Revised Brunet-Lezine scale. The distinguishability of long-term neurodevelopmental outcomes was statistically investigated. With HA, the adverse neurodevelopmental outcomes could only be distinguished from mild-moderated impairment and normal development at the thalamus with 10th percentile ADC (P = .02 and P = .03, respectively) and ADCmin (P = .03 and P = .04, respectively). Also with the conventional MRI findings, adverse outcome could be distinguished from mild-moderated impairment (P = .04) and normal development (P = .04) via cytotoxic oedema of the thalamus, corpus striatum, and diffuse cerebral cortical. The long-term adverse neurodevelopmental outcomes in newborns with asphyxia who received whole-body hypothermia treatment can be estimated similarly with volumetric ADC-HA and the conventional assessment of the ADC map. This study compares early MRI ADC-HA with neurological sequelae in term newborns with asphyxia who received whole-body hypothermia treatment. We could not find any significant difference in predicting adverse neurological sequelae between the visual-qualitative evaluation of the ADC map and HA.

Cell-Based Therapies for the Treatment of Traumatic Brain Injury: Promises and Trajectories

Traumatic Brain Injury (TBI) is a debilitating condition that poses a significant public health concern. Historically linked to motor vehicle accidents, the epidemiology of TBI has evolved. Falls now emerge as the predominant cause, particularly among older adults. Sport-related TBIs have also garnered increased attention due to concerns regarding long-term neurological sequelae. To date, therapeutic interventions remain limited and have yet to yield substantial clinical benefits. Cell-based therapies offer promising avenues for neural repair and regeneration: endogenous stem cell therapies capitalize on endogenous pools that can be triggered by the injury and further enhanced by therapeutic approaches. In contrast, exogenous cell therapies provide an exogenous source of cells. However, challenges such as age-related decline in neurogenesis, age-related inflammation, and the heterogeneity of TBI present significant hurdles to overcome. Moreover, translating stem cell research from the laboratory to clinical applications necessitates the adherence to good manufacturing practice standards, which presents distinct obstacles. Addressing these challenges requires a multifaceted approach, including careful patient selection in clinical trials, appropriate experimental models, and the optimization of therapeutic techniques. Ultimately, a combination of strategies is likely to yield the most promising outcomes in the pursuit of effective TBI therapies.

VEEV TC-83 Triggers Dysregulation of the Tryptophan-Kynurenine Pathway in the Central Nervous System That Correlates with Cognitive Impairment in Tg2576 Mice.

Neurodegenerative diseases are chronic conditions affecting the central nervous system (CNS). Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid beta in the limbic and cortical brain regions. AD is presumed to result from genetic abnormalities or environmental factors, including viral infections, which may have deleterious, long-term effects. In this study, we demonstrate that the Venezuelan equine encephalitis virus (VEEV) commonly induces neurodegeneration and long-term neurological or cognitive sequelae. Notably, the effects of VEEV infection can persistently influence gene expression in the mouse brain, suggesting a potential link between the observed neurodegenerative outcomes and long-term alterations in gene expression. Additionally, we show that alphavirus encephalitis exacerbates the neuropathological profile of AD through crosstalk between inflammatory and kynurenine pathways, generating a range of metabolites with potent effects. Using a mouse model for β-amyloidosis, Tg2576 mice, we found that cognitive deficits and brain pathology were more severe in Tg2576 mice infected with VEEV TC-83 compared to mock-infected controls. Thus, during immune activation, the kynurenine pathway plays a more active role in the VEEV TC-83-infected cells, leading to increases in the abundance of transcripts related to the kynurenine pathway of tryptophan metabolism. This pathway generates several metabolites with potent effects on neurotransmitter systems as well as on inflammation, as observed in VEEV TC-83-infected animals.

Long-term neurological and neurocognitive impairments after tick-borne encephalitis in Lithuania - a prospective study

Background The aim of this study was to characterise long-term neurological and neurocognitive sequelae after tick-borne encephalitis (TBE) in adults. Methods 98 prospective consecutive TBE patients, classified by disease severity, were included. Immediate outcomes were evaluated with Glasgow Outcome Scale (GOS) and Rankin Scale (RS). After 6 and 18 months, long-term disability was evaluated using Modified Rankin Scale (MRS) and neurocognitive assessment was performed with Matrics Consensus Cognitive Battery (MCCB), measuring processing speed, attention/vigilance, working memory, verbal learning, visual learning, reasoning/problem solving and social cognition. The MCCB results were compared to healthy age, gender and education-matched controls. Results Mild, moderate, and severe TBE was diagnosed in 53.1%, 38.8%, and 8.2% of cases, respectively. At discharge, 25.5% of the patients had major or moderate impairments (GOS) and various levels of disability in 34.7% (RS). Up to 18 months from the onset of TBE, over 20% remained with slight to moderate disability (MRS). GOS, RS and MRS scores correlated with disease severity. At 6 months after the onset, TBE patients scored significantly lower than controls in processing speed, verbal, and visual learning. Two latter domains were significantly more impaired in patients with mild TBE. Patients aged 18-39 performed significantly worse in attention/vigilance and working memory, whereas aged 60+ in verbal learning. A year later, significant improvement was observed in six of seven cognitive domains. Conclusions Long-term neurological sequelae persist in a substantial proportion of TBE patients with significant impairment in several cognitive domains, especially in younger patients and even after mild TBE.

The Syndrome of Irreversible Lithium-Effectuated Neurotoxicity: A Scoping Review.

The Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT) is a rare but concerning neurological complication resulting from lithium intoxication. Despite being reported since the 1960s, SILENT remains poorly understood and previous reviews on this topic commonly have been narrative. We therefore conducted a scoping review to assess the nature and scope of the research literature on the long-term neurological sequelae of lithium toxicity and determine the current knowledge of SILENT. A comprehensive and systematic literature search, using the MEDLINE, Embase, and Web of Science databases (from inception to July 2023), was conducted for English and Dutch articles, assessing the long-term neurological sequelae of lithium intoxication. Key information concerning clinical manifestations, risk factors, therapeutic approaches, or preventive measurements was extracted. We reviewed 91 articles, extracting information from 117 cases of SILENT. The prevailing outcome observed was persistent cerebellar dysfunction (77% of cases), often in combination with other sequelae. Other common sequelae included cognitive problems, parkinsonism, choreoathetosis, tardive dyskinesia, and peripheral neuropathy. The most common (61.4%) acute neurological symptom in the development of SILENT is an altered level of consciousness ranging from confusion to comatose states. Cerebellar sequelae were mentioned in 77% of cases as most common persistent sequelae. Antipsychotic use was mentioned in 59% of cases and fever was reported in 37.6% of cases. Scientific knowledge about this phenomenon has not advanced much since its initial reports in the 1960s and 1970s. While the use of lithium has become much more stringent than it had been in years past, and the occurrence of SILENT is rather exceptional, raising awareness about SILENT nevertheless remains crucial to avoid deleterious neurological consequences. Comprehensive, high-quality research in a systematic and standardized manner is therefore urgently needed to better understand this phenomenon.

Burden of Neurologic Health Care and Incident Neurologic Diagnoses in the Year After COVID-19 or Influenza Hospitalization.

Following the outbreak of viral infections from the severe acute respiratory syndrome coronavirus 2 virus in 2019 (coronavirus disease 2019 [COVID-19]), reports emerged of long-term neurologic sequelae in survivors. To better understand the burden of neurologic health care and incident neurologic diagnoses in the year after COVID-19 vs influenza, we performed an analysis of patient-level data from a large collection of electronic health records (EMR). We acquired deidentified data from TriNetX, a global health research network providing access to EMR data. We included individuals aged 18 years or older during index event, defined as hospital-based care for COVID-19 (from April 1, 2020, until November 15, 2021) or influenza (from 2016 to 2019). The study outcomes were subsequent health care encounters over the following year for 6 neurologic diagnoses including migraine, epilepsy, stroke, neuropathy, movement disorders, and dementia. We also created a composite of the 6 diagnoses as an incident event, which we call "incident neurologic diagnoses." We performed a 1:1 complete case nearest-neighbor propensity score match on age, sex, race/ethnicity, marital status, US census region patient residence, preindex years of available data, and Elixhauser comorbidity score. We fit time-to-event models and reported hazard ratios for COVID-19 vs influenza infection. After propensity score matching, we had a balanced cohort of 77,272 individuals with COVID-19 and 77,272 individuals with influenza. The mean age was 51.0 ± 19.7 years, 57.7% were female, and 41.5% were White. Compared with patients with influenza, patients with COVID-19 had a lower risk of subsequent care for migraine (HR 0.645, 95% CI 0.604-0.687), epilepsy (HR 0.783, 95% CI 0.727-0.843), neuropathies (HR 0.567, 95% CI 0.532-0.604), movement disorders (HR 0.644, 95% CI 0.598-0.693), stroke (HR 0.904, 95% CI 0.845-0.967), or dementia (HR 0.931, 95% CI 0.870-0.996). Postinfection incident neurologic diagnoses were observed in 2.79% of the COVID-19 cohort vs 4.91% of the influenza cohort (HR 0.618, 95% CI 0.582-0.657). Compared with a matched cohort of adults with a hospitalization or emergency department visit for influenza infection, those with COVID-19 had significantly fewer health care encounters for 6 major neurologic diagnoses over a year of follow-up. Furthermore, we found that COVID-19 infection was associated with a lower risk of an incident neurologic diagnosis in the year after infection.

The Epidemiology, Management and Therapeutic Outcomes of Subdural Empyema in Neonates with Acute Bacterial Meningitis.

Background: Subdural empyema is one of the more serious complications of bacterial meningitis and therapeutic challenges to clinicians. We aimed to evaluate the clinical characteristics, treatment, and outcome of subdural empyema in neonates with bacterial meningitis. Methods: A retrospective cohort study was conducted in two medical centers in Taiwan that enrolled all cases of neonates with subdural empyema after bacterial meningitis between 2003 and 2020. Results: Subdural empyema was diagnosed in 27 of 153 (17.6%) neonates with acute bacterial meningitis compared with cases of meningitis without subdural empyema. The demographics and pathogen distributions were comparable between the study group and the controls, but neonates with subdural empyema were significantly more likely to have clinical manifestations of fever (85.2%) and seizure (81.5%) (both p values < 0.05). The cerebrospinal fluid results of neonates with subdural empyema showed significantly higher white blood cell counts, lower glucose levels and higher protein levels (p = 0.011, 0.003 and 0.006, respectively). Neonates with subdural empyema had a significantly higher rate of neurological complications, especially subdural effusions and periventricular leukomalacia. Although the final mortality rate was not increased in neonates with subdural empyema when compared with the controls, they were often treated much longer and had a high rate of long-term neurological sequelae. Conclusions: Subdural empyema is not uncommon in neonates with acute bacterial meningitis and was associated with a high risk of neurological complications, although it does not significantly increase the final mortality rate. Close monitoring of the occurrence of subdural empyema is required, and appropriate long-term antibiotic treatment after surgical intervention may lead to optimized outcomes.

Spatio-temporal brain invasion pattern of Streptococcus pneumoniae and dynamic changes in the cellular environment in bacteremia-derived meningitis

Streptococcus pneumoniae (the pneumococcus) is the major cause of bacterial meningitis globally, and pneumococcal meningitis is associated with increased risk of long-term neurological sequelae. These include several sensorimotor functions that are controlled by specific brain regions which, during bacterial meningitis, are damaged by a neuroinflammatory response and the deleterious action of bacterial toxins in the brain. However, little is known about the invasion pattern of the pneumococcus into the brain. Using a bacteremia-derived meningitis mouse model, we combined 3D whole brain imaging with brain microdissection to show that all brain regions were equally affected during disease progression, with the presence of pneumococci closely associated to the microvasculature. In the hippocampus, the invasion provoked microglial activation, while the neurogenic niche showed increased proliferation and migration of neuroblasts. Our results indicate that, even before the outbreak of symptoms, the bacterial load throughout the brain is high and causes neuroinflammation and cell death, a pathological scenario which ultimately leads to a failing regeneration of new neurons.

Nicotinic and Muscarinic Acetylcholine Receptor Agonists Counteract Cognitive Impairment in a Rat Model of Doxorubicin-Induced Chemobrain via Attenuation of Multiple Programmed Cell Death Pathways.

Chemotherapy causes undesirable long-term neurological sequelae, chemotherapy-induced cognitive impairment (CICI), or chemobrain in cancer survivors. Activation of programmed cell death (PCD) has been proposed to implicate in the development and progression of chemobrain. Neuronal apoptosis has been extensively recognized in experimental models of chemobrain, but little is known about alternative forms of PCD in response to chemotherapy. Activation of acetylcholine receptors (AChRs) is emerging as a promising target in attenuating a wide variety of the neuronal death associated with neurodegeneration. Thus, this study aimed to investigate the therapeutic capacity of AChR agonists on cognitive function and molecular hallmarks of multiple PCD against chemotherapy neurotoxicity. To establish the chemobrain model, male Wistar rats were assigned to receive six doses of doxorubicin (DOX: 3mg/kg) via intraperitoneal injection. The DOX-treated rats received either an a7nAChR agonist (PNU-282987: 3mg/kg/day), mAChR agonists (bethanechol: 12mg/kg/day), or the two as a combined treatment. DOX administration led to impaired cognitive function via neuroinflammation, glial activation, reduced synaptic/blood-brain barrier integrity, defective mitochondrial ROS-detoxifying capacity, and dynamic imbalance. DOX insult also mediated hyperphosphorylation of Tau and simultaneously induced various PCD, including apoptosis, necroptosis, and pyroptosis in the hippocampus. Concomitant treatment with either PNU-282987, bethanechol, or a combination of the two potently attenuated neuroinflammation, mitochondrial dyshomeostasis, and Tau hyperphosphorylation, thereby suppressing excessive apoptosis, necroptosis, and pyroptosis and improving cognitive function in DOX-treated rats. Our findings suggest that activation of AChRs using their agonists effectively protected against DOX-induced neuronal death and chemobrain.

Long-term sequelae of normocephalic pansynostosis: a rare but insidious entity.

Patients with normocephalic pansynostosis, who have a grossly normal head shape, are often overlooked early in life and present late with elevated intracranial pressure (ICP) requiring timely cranial vault expansion. This study evaluates the long-term clinical outcomes of patients with normocephalic pansynostosis. We retrospectively reviewed patients with a clinical and radiographic diagnosis of primary pansynostosis who underwent vault reconstruction between 2000 and 2023. Clinical and treatment course after craniofacial interventions was followed in patients with normocephaly to assess outcomes. Thirty-five patients with primary pansynostosis were identified, of which eight (23.5%) had normocephaly and underwent initial vault expansion at a mean age of 5.0 ± 2.4years. All eight patients (50.0% male) presented with symptoms of elevated ICP including headaches (50.0%), nausea and vomiting (50.0%), and developmental delay (62.5%) and/or signs of elevated ICP including papilledema (75.0%) and radiologic thumbprinting on head computed tomography scan (87.5%). Three of the four normocephalic patients who had over 7 years of postoperative follow-up developed subjective headaches, vision changes, or learning and behavioral issues in the long-term despite successful vault reconstruction. Our longitudinal experience with this rare but insidious entity demonstrates the importance of timely intervention and frequent postoperative monitoring, which are critical to limiting long-term neurological sequelae. Multidisciplinary care by craniofacial surgery, neurosurgery, ophthalmology, and neuropsychology with follow-up into adolescence are recommended to assess for possible recurrence of elevated ICP secondary to cranio-cerebral disproportion.

Japanese encephlu emergence in Australia: the potential population at risk.

Japanese encephalitis virus (JEV), an RNA virus transmitted by Culex mosquitoes, primarily cycles between aquatic birds and mosquitoes with pigs as amplifying hosts, posing a significant global encephalitis threat. The emergence and spread of the JEV in new epidemiological regions, such as recent cases in Australia and nonendemic areas like Pune, India, raise significant concerns. With an estimated 68000 clinical cases and 13600 to 20400 deaths annually, JEV poses a substantial global health threat. The virus primarily affects children, with a case-fatality ratio of 20-30% and long-term neurological sequelae in survivors. The changing epidemiology, influenced by factors like bird migration, climate change, and increased urbanization, contributes to the geographic expansion of JEV. The recent outbreaks underscore the potential for the virus to establish itself in nonendemic regions, posing a threat to populations previously considered at low-risk. With limited treatment options and high rates of neurological complications, continued surveillance, traveler vaccination, and research into treatments are crucial to mitigate the impact of JEV on human health. The evolving scenario necessitates proactive measures to prevent and control the spread of the virus in both endemic and newly affected areas.

Repeated Ultrasound-Guided Percutaneous Intercostal Cryoneurolysis for the Management of Chronic Postmastectomy Pain Syndrome: A Case Report.

Ultrasound-guided percutaneous cryoneurolysis of the intercostal nerves is an effective analgesic modality for the management of postmastectomy pain syndrome. The duration of analgesia provided by intercostal cryoneurolysis for chronic postmastectomy pain syndrome may vary. Furthermore, limited studies have described the repeated use of cryoneurolysis to manage chronic pain in these patients. In this case report, we describe the repeated use of ultrasound-guided cryoneurolysis of the intercostal nerves to manage chronic postmastectomy pain for 2.5 years. No adverse events or long-term neurologic sequelae were reported.

Alterations in Adipocytokine Signaling Pathway and Pyroptosis in Neonatal Hypoxic-ischemic Encephalopathy.

The aims of this study are to discover dysregulated adipocytokine signaling pathway and pyroptosis-related genes to predict neonatal hypoxic-ischemic encephalopathy (HIE) occurrence. HIE is an important cause of infant death and long-term neurological sequelae. Current treatment options for HIE are relatively limited and the pathogenesis of HIE remains to be fully explored. This study investigated the alterations of adipocytokine signaling pathway and pyroptosis in neonatal HIE. To reveal the alterations of adipocytokine signaling pathway and pyroptosis relevant to HIE occurrence. Data on neonatal HIE were downloaded from the Gene Expression Omnibus (GEO) database. Pathway analyses of single-sample gene set enrichment analysis (ss- GSEA) and GSEA were performed on the adipocytokine signaling pathway and pyroptosis. Proportions of immune cells in a single sample were also calculated by ssGSEA and CIBERSORT algorithm. The relationship between the adipocytokine signaling pathway and pyroptosis was analyzed according to Pearson correlation analysis. The activities of KEGG pathways changed after the occurrence of HIE, and adipocytokine signaling pathway was activated with related overexpressed genes. For the three energy metabolisms, carbohydrate metabolism was enhanced; lipid metabolism showed increased fatty acids metabolism and decreased ability of fatty acids synthesis; metabolic levels of phosphate and phenylalanine in amino acid metabolism were elevated. Enhanced pyroptosis and relevant overexpressed genes were accompanied by increased immune cells. A positive connection between adipocytokine signaling pathway and pyroptosis was observed. These results indicated that the adipocytokine signaling pathway may promote HIE occurrence by upregulating the expression of pyroptosis-related genes, providing a novel mechanism for HIE.

Cytomegalovirus and Pregnancy: A Narrative Review.

Cytomegalovirus (CMV) infection is the most common congenital infection worldwide, affecting between 0.7% and 1% of all live births. Approximately 11% of infected newborns are symptomatic at birth, and between 30% and 40% of these are at risk of developing long-term neurological sequelae. Until recently, the lack of an effective treatment did not justify universal testing of pregnant women. In recent years, however, valacyclovir at a dose of 8 g/day has been shown to be effective in preventing vertical transmission, and ganciclovir has been shown to be effective in preventing long-term sequelae in the treatment of symptomatic neonates. The aim of this article is to review congenital CMV infection, from its epidemiology to its treatment, using the most recent studies in the literature, and to help in the decision to modify protocols for universal testing of pregnant women according to the possibilities of each locality.

Diagnostic Accuracy of Cerebrospinal Fluid Procalcitonin and Serum Procalcitonin in Adult Patients with Bacterial Meningitis: A Cross-sectional Study

Introduction: Bacterial Meningitis (BM) is a serious health problem worldwide with high mortality and permanent longterm neurological sequelae. Cerebrospinal Fluid (CSF) analysis is the cornerstone for diagnosing BM, but the lack of specificity creates a difficult clinical scenario for initiating proper treatment. Empiric antibiotic use in patients with suspected meningitis at primary care settings decreases the yield of CSF culture and alters CSF cytological and biochemical findings, making it further difficult to diagnose BM. To overcome this difficulty, there is a need for other biochemical markers with higher sensitivity and specificity. Aim: To determine the diagnostic sensitivity and specificity of Procalcitonin (PCT) in serum and CSF in patients with BM and compare its diagnostic accuracy in both sample types. Materials and Methods: A cross-sectional study was conducted in the Department of Internal Medicine at a tertiary care centre in eastern India from September 2018 to August 2020. A total of 82 adult patients with meningitis were recruited as per the protocol, and CSF analysis was done along with estimation of PCT in serum and CSF. Receiver Operating Characteristics (ROC) curve analysis of serum and CSF PCT was used to determine sensitivity and specificity with a 95% confidence interval. Results: Out of the 82 patients recruited, 30 (36.6%) had BM. CSF PCT with a cut-off value of &gt;0.45 ng/mL had a sensitivity of 86.7% and specificity of 92.3%. The sensitivity of serum PCT with a cut-off value of &gt;0.6 ng/mL was 83.3%, and specificity was 86.5%. There was no statistically significant difference in sensitivity and specificity between CSF and serum PCT in patients with BM (p-value=0.7988). Conclusion: Both serum and CSF PCT were found to have high sensitivity and specificity as markers for diagnosing BM without any statistically significant difference between them.

Insights from Rodent Models for Improving Bench-to-Bedside Translation in Traumatic Brain Injury.

Road accidents, domestic falls, and persons associated with sports and military services exhibited the concussion or contusion type of traumatic brain injury (TBI) that resulted in chronic traumatic encephalopathy. In some instances, these complex neurological aberrations pose severe brain damage and devastating long-term neurological sequelae. Several preclinical (rat and mouse) TBI models simulate the clinical TBI endophenotypes. Moreover, many investigational neuroprotective candidates showed promising effects in these models; however, the therapeutic success of these screening candidates has been discouraging at various stages of clinical trials. Thus, a correct selection of screening model that recapitulates the clinical neurobiology and endophenotypes of concussion or contusion is essential. Herein, we summarize the advantages and caveats of different preclinical models adopted for TBI research. We suggest that an accurate selection of experimental TBI models may improve the translational viability of the investigational entity.

Limited contribution of the of P2X4 receptor to LPS-induced microglial reaction in mice.

Sepsis is life-threatening condition that can trigger long-term neurological sequelae, including cognitive impairment in survivors. The pathogenesis of the so-called sickness behavior is poorly understood, but sepsis-driven neuroinflammation is thought to play a key role. Microglia are the central nervous system resident immune cells and play major roles in the induction and the control of neuroinflammatory processes. Accordingly, we recently demonstrated important microglia reaction, characterized by dramatic microglia transcriptome remodeling, in an experimental model of sepsis. Interfering with microglia pathways thus represents an interesting opportunity to tune microglia reaction towards beneficial outcomes. Purinergic signaling is central to microglia biology and controls key microglia functions. In particular, P2X4 receptors, which are highly permeable to calcium and de novo expressed in reactive microglia, seem to be an interesting target to modulate microglia reaction. Here, we investigated the impact of P2X4 receptors on the LPS-driven microglia transcriptome remodeling. Although we used complementary and sensitive biostatistical approaches, we did not measure significant impact of P2X4 deficiency onto microglia transcriptome either in homeostatic nor reactive condition. Overall, our results revealed that microglia reaction elicited by LPS-mediated sepsis is P2X4 independent and highlights the functional diversity of microglia reaction. These results also promote for the search of disease-specific targets to tune microglia reaction towards beneficial outcomes.