Prognostic risk factors for early outcomes of patients with myelomeningocele: a prospective study.

INTRODUCTION: Myelomeningocele (MMC) is a prevalent form of neural tube defect. Despite advancements in treatment, MMC still poses significant health risks, including complications leading to chronic disability and mortality. Identifying prognostic risk factors for early outcomes is crucial for tailored intervention strategies. METHODS: This prospective study involved newborns and infants diagnosed with MMC who underwent surgery between 2020 and 2023 at Urmia University of Medical Sciences. Demographic data and surgical outcomes were collected, and participants were followed up for six months. Statistical analyses were conducted using descriptive statistics, Chi-Square, and independent t-test. RESULTS: The study included 29 MMC cases, with an incidence rate of 1.4 per 10,000 live births. Lesions were predominantly located in the lumbar spine. Although mortality rates appeared to increase with ascending lesion sites, this trend was not statistically significant. Short-term outcomes revealed high morbidity and mortality rates, with neurological deficits being the most prevalent complication. Multivariable analysis identified head circumference as a significant predictor of adverse outcomes (IRR = 1.37, 95% CI = 1.02 to 1.86, p = 0.04). Furthermore, an increase in birth weight was associated with a reduction in the incidence of requiring a ventriculoperitoneal shunt (IRR = 0.99, 95% CI = 0.998 to 0.999, p = 0.02). CONCLUSION: This prospective study highlights prognostic risk factors for early outcomes in MMC patients, emphasizing the need for personalized intervention strategies. By addressing modifiable risk factors and implementing targeted interventions, healthcare providers can strive to improve outcomes and enhance the quality of life for MMC patients.

A systematic review and meta-analysis of transcranial direct-current stimulation effects on cognitive function in patients with Alzheimer's disease.

Transcranial direct-current stimulation (tDCS) appears to enhance cognitive function in Alzheimer's disease (AD). Accordingly, over the last two decades, the number of studies using tDCS for AD has grown. This study aimed to provide a quantitative assessment of the efficacy of tDCS in improving cognitive function in patients with AD. We systematically searched the literature until May 2021 to identify relevant publications for inclusion in our systematic review and meta-analysis. Eligible studies were sham-controlled trials assessing the impacts of anodal or cathodal tDCS on cognitive function in patients with AD. The outcome measure of this study was the effects of tDCS on distinct cognitive domains including memory, attention, and global cognitive function. The initial search yielded a total of 323 records. Five other articles were found using manual search of the databases. Of these, 13 publications (14 different studies) with a total of 211 patients of various degrees of AD severity underwent meta-analysis. Meta-analysis revealed the non-significant effects of tDCS on attention (0.425 SMD, 95% CI, -0.254 to 1.104, p = 0.220), and significant positive impacts on the amelioration of general cognitive measures (1.640 SMD, 95% CI, 0.782 to 2.498, p < 0.000), and memory (1.031 SMD, 95% CI, 0.688 to 1.373, p < 0.000) dysfunction in patients with AD. However, the heterogeneity of the studies were high in all subdomains of cognition (Ï°2 = 22.810, T2 = 0.552, d.f. = 5, I2 = 78.80%, p < 0.000 for attention, Ï°2 = 96.29, T2 = 1.727, d.f. = 10, I2 = 89.61%, p < 0.000 for general cognition, and Ï°2 = 7.253, T2 = 0.085, d.f. = 5, I2 = 31.06%, p = 0.203 for memory). Improved memory and general cognitive function in patients with AD was shown in this meta-analysis. However, due to the small number of studies and the high heterogeneity of the data, more high-quality studies using standardized parameters and measures are needed before tDCS can be considered as a treatment for AD.

SIMOA-based analysis of plasma NFL levels in MCI and AD patients: a systematic review and meta-analysis.

BACKGROUND: The single-molecule array assay (SIMOA)-based detection of neurofilament light (NFL) chain could be useful in diagnosing mild cognitive impairment (MCI) and Alzheimer's disease (AD). This meta-analysis aimed to evaluate the circulating concentration of NFL in AD and MCI patients compared with healthy controls using the SIMOA technique. METHODS: To this end, Google Scholar, PubMed, Scopus, Web of Science, and the reference lists of relevant articles were systematically searched for studies reporting serum NFL chain levels in healthy controls, MCI, and AD patients. Appropriate statistical methods were employed to achieve the study purpose. RESULTS: Fifteen eligible studies including 3086 patients were pooled out of a total of 347 publications. Fixed effect model analysis showed that NFL chain level was significantly higher in the serum of patients with MCI (0.361 SMD, 95% CI, 0.286-0.435, p = 0.000, I2 = 49.179) and AD (0.808 SMD, 95% CI, 0.727-0.888, p = 0.000, I2 = 39.433) compared with healthy individuals. The analysis also showed that the NFL chain levels in plasma were significantly different between patients with MCI and AD (0.436 SMD, 95% CI, 0.359-0.513, p = 0.000, I2 = 37.44). The overall heterogeneity of the studies was modest. CONCLUSIONS: This study highlights the potential of serum NFL chain detected using SIMOA in differentiating MCI, AD, and healthy controls.

Cerebrolysin® and Environmental Enrichment, Alone or in Combination, Ameliorate Anxiety- and Depressive-Like Behaviors in a Post-Ischemic Depression Model in Mice.

OBJECTIVES: This study examined the beneficial effects of cerebrolysin (CBL) and enriched environment (EE), alone or in combination, on the neurobehavioral and molecular changes in the post-ischemic depression (PID) model in mice. MATERIALS AND METHODS: PID was induced in male Balb/c mice (25-30 g) by combining the transient bilateral common carotid artery occlusion (bCCAO), twice for 5 min at the interval of 10 min, with spatial restraint stress (2 h/day) for 2 weeks, started 48 h following the establishment of bCCAO model. Animals in the treatment groups received CBL (2.5 ml/kg) and/or were housed in EE (2 h/day) for two weeks. Anxiety- and depressive-like behaviors and sociability were evaluated the day after the last experiment. Changes in the serum corticosterone level, the hippocampal oxidative stress status, inflammatory cytokines, brain-derived neurotrophic factor (BDNF), and phosphorylated cAMP response element-binding protein (p-CREB)/CREB ratio were also detected. RESULTS: PID model induced anxiety- and depressive-like behaviors and impaired social behavior. These behavioral changes were accompanied by increased serum corticosterone level, increased lipid peroxidation, decreased antioxidant enzyme activities, reduced BDNF levels and p-CREB/CREB ratio, and increased protein levels of NF-κB and Iba-1 in the hippocampus. However, treatment with CBL and/or EE reversed behavioral and molecular changes induced by PID. CONCLUSION: Our findings imply that the model mimics many manifestations of human PID, and CBL and EE treatments, separately or in combination, are beneficial in reducing anxiety- and- depressive-like behaviors in this model.

Effects of transdermal nicotine delivery on cognitive outcomes: A meta-analysis.

OBJECTIVE: By the association of nicotinic acetylcholine receptors in the brain, nicotine in the therapeutic window lowers neuronal damage and raises protective factors. These data, however, are contradicted by other findings. Here, we assessed the effects of transdermal nicotine administration on cognitive functions in healthy non-smoker adults by systematic review and meta-analysis of clinical trials. METHODS: We included reports of clinical trials comparing the effects of nicotine patches with placebo in healthy non-smoking adults. The main outcome was the impact of nicotine patches on overall cognitive function with a focus on attention and memory. Standard meta-analytic and statistical methods measured the effect of transdermal nicotine compared with placebo patches. RESULTS: We included 31 publications involving 978 subjects. Nicotine patches boosted cognitive function in healthy adults (0.233 SMD, 95%CI, 0.111-0.355, p < .001). Overall heterogeneity of the studies was found to be modest (Ï°2  = 68.24, T2  = 0.07, I2  = 50.17%, p < .001). Also, nicotine patches improved attention (0.231 SMD, 95%CI, 0.106-0.356, p < .001). We found the inter-study heterogeneity to be low (Ï°2  = 40.95, T2  = 0.03, I2  = 34.07%, p = .042). Further, the enhancement of memory by transdermal nicotine did not reach statistical significance in normal subjects (0.270 SMD, 95% CI, -0.293-0.833, p = .347). Also, high inter-study heterogeneity was found among studies (Ï°2  = 27.25, T2  = 0.43, I2  = 77.98%, p < .001). CONCLUSION: The meta-analysis showed that transdermal nicotine had statistically significant positive effects on attention, and non-significant effects on memory, in healthy non-smoking adults. The results encourage further studies of the therapeutic potential of nicotine patches in disorders of cognition.

Heat stress aggravates oxidative stress, apoptosis, and endoplasmic reticulum stress in the cerebellum of male C57 mice.

BACKGROUND: The current study was set to assess the effect of heat stress exposure on oxidative stress, apoptosis, and endoplasmic reticulum stress markers in the cerebellum of male mice. METHODS: Fifty male C57BL/6 mice were assigned to five groups of (I) control, (II) heat stress (HS)7, (III) HS14, (IV) HS21, and (V) HS42 groups. Animals in the control group were not exposed to HS. Mice in the II-V groups were exposed to HS once a day over 7, 14, 21, and 42 days, respectively. Cerebellar reactive oxygen species (ROS) levels, expression of heat shock protein (HSP)70 and caspase 3 as well as endoplasmic reticulum stress-related proteins (PERK, p-PERK, CHOP, and Full-length ATF-6) expression were determined on the 7th, 14th, 21st, and 42nd days. RESULTS: ROS levels and HSP70 expression increased following HS on the 14th, 21st, and 42nd days and the 7th, and 14th days with a peak level of expression on the 14th day following HS. HSP70 levels decreased afterward on the 21st and 42nd days compared with the control group. Besides, exposure to HS for 14, 21, and 42 days resulted in a significant increase in the CHOP and p-PERK levels in the cerebellum compared with the control group. Heat exposure also increased protein expression of cleaved caspase 3 and active ATF-6/Full-length ATF-6 on the 21st and 42nd days in the cerebellum compared with the control animals. CONCLUSION: These findings indicated that chronic HS augmented oxidative stress, endoplasmic reticulum stress, and apoptosis pathways in the cerebellum of mice.

The correlation between circulating inflammatory, oxidative stress, and neurotrophic factors level with the cognitive outcomes in multiple sclerosis patients.

INTRODUCTION: Changes in the levels of circulating markers of inflammation, oxidative stress, and neurotrophic factors might be a good candidate for the prediction of cognitive impairment in multiple sclerosis (MS). Here, the correlation between the mentioned circulating markers with the Cambridge neuropsychological test automated battery (CANTAB) task outcomes was determined in MS patients. METHODS: The CANTAB (paired-associate learning (PAL), reaction time (RTI), rapid visual information processing (RVP), and spatial working memory tasks (SWM)) was completed by the patients. Accordingly, the serum levels of interferon-γ (INF-γ), C-reactive protein (CRP), ciliary neurotrophic factor (CNTF), glial cell line-derived neurotrophic factor (GDNF), and brain-derived neurotrophic factor (BDNF), malondialdehyde (MDA), total antioxidant capacity (TAC), and the acetylcholine esterase (AChE) activity were measured. Cognitive impairment status and the correlation between the circulating factors with the CANTAB outcomes were determined. RESULTS: The cognitively impaired (CI) patients appropriately differentiated from not cognitively impaired (NCI) ones using the CANTAB tasks. The serum levels of MDA, TAC, CRP, INF-γ, and GDNF correlated with the cognitive scores in MS patients (p < 0.05). After adjusting for age, sex, disease duration, and disability levels (covariates in a regression model), the MDA, INF-γ, and GDNF factors levels were statistically different between CI and NCI groups (p < 0.05). DISCUSSION: The mentioned markers might predict the cognitive impairment progress and be used as an index of its detection, in addition to neuropsychological assessments, in MS patients.

Diagnostic manifestations of total hemispheric glucose metabolism ratio in neuronal network diaschisis: diagnostic implications in Alzheimer's disease and mild cognitive impairment.

PURPOSE: We tested the hypothesis that lateralized hemispheric glucose metabolism may have diagnostic implications in Alzheimer's disease (AD) and mild cognitive impairment (MCI). METHODS: We performed FDG-PET/CT in 23 patients (mean age 63.7 years, range 50-78, 17 females) diagnosed with AD (n = 15) or MCI (n = 8) during a six-month period in 2014. Ten neurologically healthy individuals (HIs) (mean age 62.5 years, range 43-75, 5 females) served as controls. A neuroimaging expert provided visual assessment of diaschisis. The total hemispheric glucose metabolism ratio (THGr) was calculated, and with area-under the curve of receiver operating characteristics (AUC-ROC) we generated a "Network Diaschisis Test (NDT)". RESULTS: The qualitative detection of cerebral (Ce) and cerebellar (Cb) diaschisis was 7/15 (47%), 0/8 (0%), and 0/10 (0%) in AD, MCI, and HI groups, respectively. Median cerebral THGr was 0.68 (range 0.43-0.99), 0.86 (range 0.64-0.98), and 0.95 (range 0.65-1.00) for AD, MCI, and HI groups, respectively (p = 0.04). Median cerebellar THGr was, respectively, 0.70 (range 0.18-0.98), 0.70 (range 0.48-0.81), and 0.84 (range 0.75-0.96) (p = 0.0138). A positive NDT yielded a positive predictive value of 100% for the presence of AD or MCI and a 86% negative predictive value for healthy brain. Moreover, the diagnostic manifestation of THGr between MCI and AD led to a positive predictive value of 100% for AD, but a negative predictive value of 42.9% for MCI. CONCLUSION: Patients with AD or MCI had more pronounced diaschisis, lateralized hemispheric glucose metabolism and lower THGr compared to healthy controls. The NDT distinguished AD and MCI patients from HIs, and AD from MCI patients with a high positive predictive value and moderate and low negative predictive values. THGr can be a straightforward source of investigating neuronal network diaschisis in AD and MCI and in other cerebral diseases, across institutions.

Cinnarizine/betahistine combination vs. the respective monotherapies in acute peripheral vertigo: a randomized triple-blind placebo-controlled trial.

PURPOSE: To compare the efficacy of cinnarizine/betahistine combination with the respective monotherapies in patients with acute peripheral vertigo (APV). METHOD: A randomized, triple-blind placebo-controlled phase III trial was performed on 162 patients with APV to compare the efficacy of cinnarizine/betahistine combination with the respective monotherapies. Patients were randomly allocated into three groups (n = 54 each) of Bet. (betahistine and placebo), Cin. (cinnarizine and placebo), and Bet. + Cin. (betahistine and cinnarizine). The first group received cinnarizine tablets (25 mg) plus placebo three times a day, the second group received betahistine tablets (8 mg) plus placebo three times a day, and the third group received betahistine (8 mg) plus cinnarizine (25 mg) combination three times a day. The treatments were continued for 1 week. Patients were followed up to 3 days and 1 week after initiation of the treatments for changes in vertigo severity measured by visual grading scale (VAS), mean vertigo score (MVS), and mean concomitant symptom score (MCSS). RESULTS: Results showed a significant difference between the groups in VAS (p = 0.001), MVS (p = 0.0001), and MCSS (p = 0.0001) at 1-week follow-up, where the respective values were significantly lower in the Cin. + Bet. group as compared with the respective monotherapies. Efficacy and tolerability of the treatment were found to be higher in the Cin. + Bet. group at 3-day and 1-week follow-up periods (p = 0.0001, for all comparisons). None of the patients reported any side effects during the study. CONCLUSION: This study indicated the superiority of the cinnarizine/betahistine combination over the respective monotherapies in the treatment of APV. TRIAL REGISTRATION: IRCT20130710013947N9.

Very low birth weight is associated with brain structure abnormalities and cognitive function impairments: A systematic review.

Very low birth weight (VLBW) children are at risk of structural brain abnormalities and neurocognitive deficits. Since survival rate of the very low birth weight infants has increased over the past decade, a better understanding of the long-term neurocognitive outcomes is needed. The present systematic review investigated the association between VLBW and cognitive function as well as brain structure. PubMed/Medline, Google Scholar, Scopus and Web of Science databases were searched up from January 2000 to January 2015. The study was restricted to the articles that were about VLBW and its association with cognitive function and brain structure. The initial search yielded 721 articles. There were 44 studies eligible for inclusion after applying the exclusion criteria: 24 follow-up, 14 cohort, and 6 longitudinal studies. Based on this systematic review, we suggest that VLBW is positively related to several cognitive problems and brain structure abnormalities. These findings provide evidence about the importance of early assessment of cognitive development and brain structure to identify at-risk children and provide their specific requirements as early as possible.

Chronic Administration of Rosa canina Hydro-Alcoholic Extract Attenuates Depressive-Like Behavior and Recognition Memory Impairment in Diabetic Mice: A Possible Role of Oxidative Stress.

OBJECTIVE: This study was designed to evaluate whether chronic Rosa canina (RC) extract administration could improve recognition memory and depressive-like behavior in diabetic mice. MATERIALS AND METHODS: Seventy-five male albino mice (25-30 g) were randomly divided into 5 groups (15 in each group). A single intraperitoneal injection of 200 mg/kg streptozotocin (STZ) was administered to the mice to induce diabetes. The control group received normal saline, and the diabetic groups received normal saline or 50, 250, and 500 mg/kg of RC extract for 28 days. The mice were weighed each week. Recognition memory and depressive-like behavior were assessed using forced swimming and novel object recognition (NOR) tests, respectively. Malondialdehyde (MDA) levels and total antioxidant capacity (TAC) were measured in the mouse brain homogenate to evaluate oxidative stress. Statistical analysis was conducted using SPSS, version 22. RESULTS: The groups receiving 250 or 500 mg/kg RC had significantly lower immobility time (159.4 ± 4.7 and 150.1 ± 3.1 s) compared to the sham control group (192.1 ± 7.8 s) in the forced swimming test, and a higher discrimination index (0.39 ± 0.02 and 0.48 ± 0.03) was seen in diabetic animals in the NOR task compared to the sham control group (0.2 ± 0.01). Also, the groups receiving treatment with RC (250 and 500 mg/kg) had significantly higher TAC (0.92 ± 0.04 and 0.96 ± 0.05 mmol/L) and lower MDA (0.76 ± 0.02 and 0.67 ± 0.03 nmol/mg protein) levels in the brains in comparison to the model group. In the 3rd and 4th weeks of study, the RC-treated mice (250 and 500 mg/kg) gained more weight (31.2 ± 0.3 and 32.4 ± 0.3 g, and 31.3 ± 0.2 and 33.7 ± 0.3 g, respectively) than the diabetic group (30 ± 0.2 and 29.6 ± 0.3 g). CONCLUSION: This study showed that RC attenuated impairment of recognition memory and depressive-like behavior probably through modulation of oxidative stress in an STZ model of diabetes in mouse brains.

Permissive role of cytosolic pH acidification in neurodegeneration: A closer look at its causes and consequences.

The maintenance of cytosolic pH in its physiological range is required for normal neuronal activity, and even minor alterations can have serious consequences. This Review summarizes the current understanding of the conditions that are associated with cytosolic pH disruption and that lead to abnormal cytosolic acidification. Oxidative stress results in cytosolic acidification, and this plays a crucial role in the emergence of apoptosis in protein misfolding and excitotoxicity, ultimately leading to irreversible neuronal damage. Through the identification of mechanisms by which intraneuronal pH acidification promotes neurodegeneration, we may identify new approaches for preventing and treating neurodegenerative disorders. © 2016 Wiley Periodicals, Inc.

Astrocytic and microglial nicotinic acetylcholine receptors: an overlooked issue in Alzheimer's disease.

It is increasingly recognized that astrocytes and microglia-associated dysfunction contribute to AD pathology. In addition, glial nicotinic acetylcholine receptors (nAChRs) play a role in AD-related phenomena, such as neuron survival, synaptic plasticity, and memory. From mechanistic point of view, the glial regulation of pro-inflammatory cytokines, as common contributors in AD, is modulated by nAChRs. Astrocytic and microglial nAChRs contribute to Aß metabolism, including Aß phagocytosis and degradation as well as Aß-related oxidative stress and neurotoxicity. These receptors are also involved in neurotransmission and gliotransmission through indirect interaction with N-Methyl-D-aspartate (NMDA) and a-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid (AMPA) receptors as well as gamma-aminobutyric acid (GABA) and intracellular calcium regulation. In addition, glial nAChRs participate in trophic factors-induced neuroprotection. This review gathers the most recent advances along with the previous data on astrocytic and microglial nAChRs role in AD pathogenesis.

Cargo trafficking in Alzheimer's disease: the possible role of retromer.

Alzheimer's disease (AD) as one of the on going neurological disorders is initiated and progressed by multiple pathological pathways. Cargoes trafficking pathways,such as recycling, play a crucial role in the pathogenesis of AD. One of the major constituents of this trafficking system in neurons is retromer which acts in endosomal sorting machinery. Defective retromer disrupts recycling of cargoes from endosomes to Golgi and leads to its mis-trafficking which may subsequently leads to AD. Also, retromer-related cargo trafficking could trigger amyloidogenic pathway and beta-amyloid production. Wingless is another cargo in Wnt pathways and its trafficking is mediated by retromer. Retromer malfunction leads to lack of Wnt and subsequent AD-related pathogenesis. Also, retromer plays role in synaptic receptor trafficking in physiologic and pathologic conditions. This review is brief survey on the recent published literatures about pathogenesis of retromer-related trafficking in amyloid precursor protein pathways, Wnt signaling, synaptic function, and also revised the structural role of retromer in AD progression.

The interplay of microRNAs and post-ischemic glutamate excitotoxicity: an emergent research field in stroke medicine.

Stroke is the second leading cause of death and the most common cause of adult disabilities among elderlies. It involves a complex series of mechanisms among which, excitotoxicity is of great importance. Also, miRNAs appear to play role in post-stroke excitotoxicity, and changes in their transcriptome occur right after cerebral ischemia. Recent data indicate that specific miRNAs such as miRNA-223, miRNA-181, miRNA-125a, miRNA-125b, miRNA-1000, miRNA-132 and miRNA-124a regulate glutamate neurotransmission and excitotoxicity during stroke. However, limitations such as poor in vivo stability, side effects and inappropriate biodistribution in miRNA-based therapies still exist and should be overcome before clinical application. Thence, investigation of the effect of application of these miRNAs after the onset of ischemia is a pivotal step for manipulating these miRNAs in clinical use. Given this, present review concentrates on miRNAs roles in post-ischemic stroke excitotoxicity.

Amyloid-beta: a crucial factor in Alzheimer's disease.

Alzheimer's disease (AD) is the most prevalent form of dementia which affects people older than 60 years of age. In AD, the dysregulation of the amyloid-beta (Aß) level leads to the appearance of senile plaques which contain Aß depositions. Aß is a complex biological molecule which interacts with many types of receptors and/or forms insoluble assemblies and, eventually, its nonphysiological depositions alternate with the normal neuronal conditions. In this situation, AD signs appear and the patients experience marked cognitional disabilities. In general, intellect, social skills, personality, and memory are influenced by this disease and, in the long run, it leads to a reduction in quality of life and life expectancy. Due to the pivotal role of Aß in the pathobiology of AD, a great deal of effort has been made to reveal its exact role in neuronal dysfunctions and to finding efficacious therapeutic strategies against its adverse neuronal outcomes. Hence, the determination of its different molecular assemblies and the mechanisms underlying its pathological effects are of interest. In the present paper, some of the well-established structural forms of Aß, its interactions with various receptors and possible molecular and cellular mechanisms underlying its neurotoxicity are discussed. In addition, several Aß-based rodent models of AD are reviewed.

Investigating the Safety and Efficacy of Therapeutic Hypothermia in Pediatric Severe Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

BACKGROUND: Prior guidelines recommended maintaining normothermia following traumatic brain injury (TBI), but recent studies suggest therapeutic hypothermia as a viable option in pediatric cases. However, some others demonstrated a higher mortality rate. Hence, the impact of hypothermia on neurological symptoms and overall survival remains contentious. METHODS: We conducted a systematic review and meta-analysis to evaluate the effects of hypothermia on neurological outcomes in pediatric TBI patients. The PubMed/Medline, Scopus, and Web of Science databases were searched until 1 January 2024 and data were analyzed using appropriate statistical methods. RESULTS: A total of eight studies, comprising nine reports, were included in this analysis. Our meta-analysis did not reveal significant differences in mortality (RR = 1.58; 95% CI = 0.89-2.82, p = 0.055), infection (RR = 0.95: 95% CI = 0.79-1.1, p = 0.6), arrhythmia (RR = 2.85: 95% CI = 0.88-9.2, p = 0.08), hypotension (RR = 1.54: 95% CI = 0.91-2.6, p = 0.10), intracranial pressure (SMD = 5.07: 95% CI = -4.6-14.8, p = 0.30), hospital length of stay (SMD = 0.10; 95% CI = -0.13-0.3, p = 0.39), pediatric intensive care unit length of stay (SMD = 0.04; 95% CI = -0.19-0.28, p = 0.71), hemorrhage (RR = 0.86; 95% CI = 0.34-2.13, p = 0.75), cerebral perfusion pressure (SMD = 0.158: 95% CI = 0.11-0.13, p = 0.172), prothrombin time (SMD = 0.425; 95% CI = -0.037-0.886, p = 0.07), and partial thromboplastin time (SMD = 0.386; 95% CI = -0.074-0.847, p = 0.10) between the hypothermic and non-hypothermic groups. However, the heart rate was significantly lower in the hypothermic group (-1.523 SMD = -1.523: 95% CI = -1.81--1.22 p < 0.001). CONCLUSIONS: Our findings challenge the effectiveness of therapeutic hypothermia in pediatric TBI cases. Despite expectations, it did not significantly improve key clinical outcomes. This prompts a critical re-evaluation of hypothermia's role as a standard intervention in pediatric TBI treatment.

Reinterpreting published tDCS results in terms of a cranial and cervical nerve co-stimulation mechanism.

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation method that has been used to alter cognition in hundreds of experiments. During tDCS, a low-amplitude current is delivered via scalp electrodes to create a weak electric field in the brain. The weak electric field causes membrane polarization in cortical neurons directly under the scalp electrodes. It is generally assumed that this mechanism causes the observed effects of tDCS on cognition. However, it was recently shown that some tDCS effects are not caused by the electric field in the brain but rather via co-stimulation of cranial and cervical nerves in the scalp that also have neuromodulatory effects that can influence cognition. This peripheral nerve co-stimulation mechanism is not controlled for in tDCS experiments that use the standard sham condition. In light of this new evidence, results from previous tDCS experiments could be reinterpreted in terms of a peripheral nerve co-stimulation mechanism. Here, we selected six publications that reported tDCS effects on cognition and attributed the effects to the electric field in the brain directly under the electrode. We then posed the question: given the known neuromodulatory effects of cranial and cervical nerve stimulation, could the reported results also be understood in terms of tDCS peripheral nerve co-stimulation? We present our re-interpretation of these results as a way to stimulate debate within the neuromodulation field and as a food-for-thought for researchers designing new tDCS experiments.

Understanding Neuromodulation Pathways in tDCS: Brain Stem Recordings in Rat During Trigeminal Nerve Direct Current Stimulation.

Background: Recent evidence suggests that transcranial direct current stimulation (tDCS) indirectly influences brain activity through cranial nerve pathways, particularly the trigeminal nerve. However, the electrophysiological effects of direct current (DC) stimulation on the trigeminal nerve (DC-TNS) and its impact on trigeminal nuclei remain unknown. These nuclei exert control over brainstem centers regulating neurotransmitter release, such as serotonin and norepinephrine, potentially affecting global brain activity. Objectives: To investigate how DC-TNS impacts neuronal activity in the principal sensory nucleus (NVsnpr) and the mesencephalic nucleus of the trigeminal nerve (MeV). Methods: Twenty male Sprague Dawley rats (n=10 each nucleus) were anesthetized with urethane. DC stimulation, ranging from 0.5 to 3 mA, targeted the trigeminal nerve's marginal branch. Simultaneously, single-unit electrophysiological recordings were obtained using a 32-channel silicon probe, comprising three one-minute intervals: pre-stimulation, DC stimulation, and post-stimulation. Xylocaine was administered to block the trigeminal nerve as a control. Results: DC-TNS significantly increased neuronal spiking activity in both NVsnpr and MeV, returning to baseline during the post-stimulation phase. When the trigeminal nerve was blocked with xylocaine, the robust 3 mA trigeminal nerve DC stimulation failed to induce increased spiking activity in the trigeminal nuclei. Conclusion: Our results offer initial empirical support for trigeminal nuclei activity modulation via DC-TNS. This discovery supports the hypothesis that cranial nerve pathways may play a pivotal role in mediating tDCS effects, setting the stage for further exploration into the complex interplay between peripheral nerves and neural modulation techniques. Highlights: Direct current stimulation of the trigeminal nerve (DC-TNS) modulates neural activity in rat NVsnpr and MeV.Xylocaine administration reversibly blocks the DC-TNS effect on neural responses.Trigeminal nerve stimulation should be considered a possible mechanism of action of tDCS.