Neural Cells Research Articles

Zika viruses encode 5′ upstream open reading frames affecting infection of human brain cells

Zika virus (ZIKV), an emerging mosquito-borne flavivirus, is associated with congenital neurological complications. Here, we investigate potential pathological correlates of virus gene expression in representative ZIKV strains through RNA sequencing and ribosome profiling. In addition to the single long polyprotein found in all flaviviruses, we identify the translation of unrecognised upstream open reading frames (uORFs) in the genomic 5′ region. In Asian/American strains, ribosomes translate uORF1 and uORF2, whereas in African strains, the two uORFs are fused into one (African uORF). We use reverse genetics to examine the impact on ZIKV fitness of different uORFs mutant viruses. We find that expression of the African uORF and the Asian/American uORF1 modulates virus growth and tropism in human cortical neurons and cerebral organoids, suggesting a potential role in neurotropism. Although the uORFs are expressed in mosquito cells, we do not see a measurable effect on transmission by the mosquito vector in vivo. The discovery of ZIKV uORFs sheds new light on the infection of the human brain cells by this virus and raises the question of their existence in other neurotropic flaviviruses.

Speech based detection of Alzheimer’s disease: a survey of AI techniques, datasets and challenges

Alzheimer’s disease (AD) is a growing global concern, exacerbated by an aging population and the high costs associated with traditional detection methods. Recent research has identified speech data as valuable clinical information for AD detection, given its association with the progressive degeneration of brain cells and subsequent impacts on memory, cognition, and language abilities. The ongoing demographic shift toward an aging global population underscores the critical need for affordable and easily available methods for early AD detection and intervention. To address this major challenge, substantial research has recently focused on investigating speech data, aiming to develop efficient and affordable diagnostic tools that align with the demands of our aging society. This paper presents an in-depth review of studies from 2018–2023 utilizing speech for AD detection. Following the PRISMA protocol and a two-stage selection process, we identified 85 publications for analysis. In contrast to previous literature reviews, this paper places a strong emphasis on conducting a rigorous comparative analysis of various Artificial Intelligence (AI) based techniques, categorizing them meticulously based on underlying algorithms. We perform an exhaustive evaluation of research papers leveraging common benchmark datasets, specifically ADReSS and ADReSSo, to assess their performance. In contrast to previous literature reviews, this work makes a significant contribution by overcoming the limitations posed by the absence of standardized tasks and commonly accepted benchmark datasets for comparing different studies. The analysis reveals the dominance of deep learning models, particularly those leveraging pre-trained models like BERT, in AD detection. The integration of acoustic and linguistic features often achieves accuracies above 85%. Despite these advancements, challenges persist in data scarcity, standardization, privacy, and model interpretability. Future directions include improving multilingual recognition, exploring emerging multimodal approaches, and enhancing ASR systems for AD patients. By identifying these key challenges and suggesting future research directions, our review serves as a valuable resource for advancing AD detection techniques and their practical implementation.

Candidate Molecular Biomarkers of Traumatic Brain Injury: A Systematic Review

Traumatic brain injury (TBI) is one of the leading causes of mortality and disability among young and middle-aged individuals. Adequate and timely diagnosis of primary brain injuries, as well as the prompt prevention and treatment of secondary injury mechanisms, significantly determine the potential for reducing mortality and severe disabling consequences. Therefore, it is crucial to have objective markers that indicate the severity of the injury. A number of molecular factors—proteins and metabolites—detected in the blood immediately after trauma and associated with the development and severity of TBI can serve in this role. TBI is a heterogeneous condition with respect to its etiology, clinical form, and genesis, being accompanied by brain cell damage and disruption of blood–brain barrier permeability. Two oppositely directed flows of substances and signals are observed: one is the flow of metabolites, proteins, and nucleic acids from damaged brain cells into the bloodstream through the damaged blood–brain barrier; the other is the infiltration of immune cells (neutrophils and macrophages) and serological proteins. Both flows aggravate brain tissue damage after TBI. Therefore, it is extremely important to study the key signaling events that regulate these flows and repair the damaged tissues, as well as to enhance the effectiveness of treatments for patients after TBI.

Cell-cell interaction determines cell fate of mesoderm-derived cell in tongue development through Hh signaling.

Dysfunction of primary cilia leads to genetic disorder, ciliopathies, which shows various malformations in many vital organs such as brain. Multiple tongue deformities including cleft, hamartoma, and ankyloglossia are also seen in ciliopathies, which yield difficulties in fundamental functions such as mastication and vocalization. Here, we found these tongue anomalies in mice with mutation of ciliary protein. Abnormal cranial neural crest-derived cells (CNCC) failed to evoke Hh signal for differentiation of mesoderm-derived cells into myoblasts, which resulted in abnormal differentiation of mesoderm-derived cells into adipocytes. The ectopic adipose subsequently arrested tongue swelling formation. Ankyloglossia was caused by aberrant cell migration due to lack of non-canonical Wnt signaling. In addition to ciliopathies, these tongue anomalies are often observed as non-familial condition in human. We found that these tongue deformities could be reproduced in wild-type mice by simple mechanical manipulations to disturb cellular processes which were disrupted in mutant mice. Our results provide hints for possible future treatment in ciliopathies.

Expression of pregnenolone-synthesizing enzymes CYP11A1 and CYP1B1 in the human, rat, and mouse brain

The central nervous system (CNS) is capable of synthesizing steroids for modulating essential functions such as neurotransmission, neuroplasticity, and neuroinflammation. These locally synthesized steroids, called neurosteroids, are produced through the conversion of cholesterol into the major steroid precursor pregnenolone, followed by downstream metabolism to form various steroids such as progesterone and allopregnanolone. Given that changes in neurosteroids are implicated in many neurological and psychiatric disorders, understanding the neurosteroidogenesis pathway is crucial. Recent studies have demonstrated an alternative pathway for the biosynthesis of pregnenolone, which is classically produced by CYP11A1 but was found instead to be made by CYP1B1 in human glial cells. However, numerous studies have demonstrated Cyp11a1 expression and activity in rodent brain tissue and brain cells. To elucidate whether species differences exist for the pregnenolone synthesis enzyme in human and rodent brains, we sought to directly compare the expression levels of CYP11A1 and CYP1B1 in human, rat, and mouse CNS tissues. We found that CYP1B1 mRNA expression was significantly higher than that of CYP11A1 in almost all CNS brain regions in human, rat, and mouse. The exception is in the mouse cerebral cortex, where Cyp11a1 RNA was more abundant than Cyp1b1. However, Cyp11a1 protein was clearly detectable in rodent CNS while completely undetectable in human brain. In contrast, the presence of CYP1B1 protein can be observed in both human and rodent brains. These results suggest that CYP1B1 is likely the dominant pregnenolone synthesis enzyme in the human brain, while rodent brains may use both Cyp11a1 and Cyp1b1.

Transcriptome and proteome profiling reveals TREM2-dependent and -independent glial response and metabolic perturbation in an Alzheimer’s mouse model

Elucidating the intricate molecular mechanisms of Alzheimer's disease (AD) requires a multidimensional analysis incorporating various omics data. In this study, we employed transcriptome and proteome profiling of AppNL-G-F, a human APP knock-in model of amyloidosis, at the early and mid-stages of amyloid-beta (Aβ) pathology to delineate the impacts of Aβ deposition on brain cells. By contrasting AppNL-G-F mice with TREM2 (Triggering receptor expressed on myeloid cells 2) knockout models, our study further investigates the role of TREM2, a well-known AD risk gene, in influencing microglial responses to Aβ pathology. Our results highlight altered microglial states as a central feature of Aβ pathology, characterized by the significant upregulation of microglia-specific genes related to immune responses such as complement system and antigen presentation, and catabolic pathways such as phagosome formation and lysosome biogenesis. The absence of TREM2 markedly diminishes the induction of these genes, impairs Aβ clearance, and exacerbates dystrophic neurite formation. Importantly, TREM2 is required for the microglial engagement with Aβ plaques and the formation of compact Aβ plaque cores. Furthermore, this study reveals substantial disruptions in energy metabolism and protein synthesis, signaling a shift from anabolism to catabolism in response to Aβ deposition. This metabolic alteration, coupled with a decrease in synaptic protein abundance, occurs independently of TREM2, suggesting the direct effects of Aβ deposition on synaptic integrity and plasticity. In summary, our findings demonstrate altered microglial states and metabolic disruption following Aβ deposition, offering mechanistic insights into Aβ pathology and highlighting the potential of targeting these pathways in AD therapy.

Spatiotemporal modeling reveals high-resolution invasion states in glioblastoma

BackgroundDiffuse invasion of glioblastoma cells through normal brain tissue is a key contributor to tumor aggressiveness, resistance to conventional therapies, and dismal prognosis in patients. A deeper understanding of how components of the tumor microenvironment (TME) contribute to overall tumor organization and to programs of invasion may reveal opportunities for improved therapeutic strategies.ResultsTowards this goal, we apply a novel computational workflow to a spatiotemporally profiled GBM xenograft cohort, leveraging the ability to distinguish human tumor from mouse TME to overcome previous limitations in the analysis of diffuse invasion. Our analytic approach, based on unsupervised deconvolution, performs reference-free discovery of cell types and cell activities within the complete GBM ecosystem. We present a comprehensive catalogue of 15 tumor cell programs set within the spatiotemporal context of 90 mouse brain and TME cell types, cell activities, and anatomic structures. Distinct tumor programs related to invasion align with routes of perivascular, white matter, and parenchymal invasion. Furthermore, sub-modules of genes serving as program network hubs are highly prognostic in GBM patients.ConclusionThe compendium of programs presented here provides a basis for rational targeting of tumor and/or TME components. We anticipate that our approach will facilitate an ecosystem-level understanding of the immediate and long-term consequences of such perturbations, including the identification of compensatory programs that will inform improved combinatorial therapies.

Transcriptional responses in a mouse model of silicone wire embolization induced acute retinal artery ischemia and reperfusion.

Acute retinal ischemia and ischemia-reperfusion injury are the primary causes of retinal neural cell death and vision loss in retinal artery occlusion (RAO). The absence of an accurate mouse model for simulating the retinal ischemic process has hindered progress in developing neuroprotective agents for RAO. We developed a unilateral pterygopalatine ophthalmic artery occlusion (UPOAO) mouse model using silicone wire embolization combined with carotid artery ligation. The survival of retinal ganglion cells and visual function were evaluated to determine the duration of ischemia. Immunofluorescence staining, optical coherence tomography, and haematoxylin and eosin staining were utilized to assess changes in major neural cell classes and retinal structure degeneration at two reperfusion durations. Transcriptomics was employed to investigate alterations in the pathological process of UPOAO following ischemia and reperfusion, highlighting transcriptomic differences between UPOAO and other retinal ischemia-reperfusion models. The UPOAO model successfully replicated the acute interruption of retinal blood supply observed in RAO. 60 min of Ischemia led to significant loss of major retinal neural cells and visual function impairment. Notable thinning of the inner retinal layer, especially the ganglion cell layer, was evident post-UPOAO. Temporal transcriptome analysis revealed various pathophysiological processes related to immune cell migration, oxidative stress, and immune inflammation during the non-reperfusion and reperfusion periods. A pronounced increase in microglia within the retina and peripheral leukocytes accessing the retina was observed during reperfusion periods. Comparison of differentially expressed genes (DEGs) between the UPOAO and high intraocular pressure models revealed specific enrichments in lipid and steroid metabolism-related genes in the UPOAO model. The UPOAO model emerges as a novel tool for screening pathogenic genes and promoting further therapeutic research in RAO.

Transcriptional responses in a mouse model of silicone wire embolization induced acute retinal artery ischemia and reperfusion

Acute retinal ischemia and ischemia-reperfusion injury are the primary causes of retinal neural cell death and vision loss in retinal artery occlusion (RAO). The absence of an accurate mouse model for simulating the retinal ischemic process has hindered progress in developing neuroprotective agents for RAO. We developed a unilateral pterygopalatine ophthalmic artery occlusion (UPOAO) mouse model using silicone wire embolization combined with carotid artery ligation. The survival of retinal ganglion cells and visual function were evaluated to determine the duration of ischemia. Immunofluorescence staining, optical coherence tomography, and haematoxylin and eosin staining were utilized to assess changes in major neural cell classes and retinal structure degeneration at two reperfusion durations. Transcriptomics was employed to investigate alterations in the pathological process of UPOAO following ischemia and reperfusion, highlighting transcriptomic differences between UPOAO and other retinal ischemia-reperfusion models. The UPOAO model successfully replicated the acute interruption of retinal blood supply observed in RAO. 60 min of Ischemia led to significant loss of major retinal neural cells and visual function impairment. Notable thinning of the inner retinal layer, especially the ganglion cell layer, was evident post-UPOAO. Temporal transcriptome analysis revealed various pathophysiological processes related to immune cell migration, oxidative stress, and immune inflammation during the non-reperfusion and reperfusion periods. A pronounced increase in microglia within the retina and peripheral leukocytes accessing the retina was observed during reperfusion periods. Comparison of differentially expressed genes (DEGs) between the UPOAO and high intraocular pressure models revealed specific enrichments in lipid and steroid metabolism-related genes in the UPOAO model. The UPOAO model emerges as a novel tool for screening pathogenic genes and promoting further therapeutic research in RAO.

The transcription elongation factors Spt4 and Spt5 control neural progenitor proliferation and are implicated in neuronal remodeling during Drosophila mushroom body development

Spt4 and Spt5 form the DRB sensitivity inducing factor (DSIF) complex that regulates transcription elongation at multiple steps including promotor-proximal pausing, processivity and termination. Although this implicated a general role in transcription, several studies pointed to smaller sets of target genes and indicated a more specific requirement in certain cellular contexts. To unravel common or distinct functions of Spt4 and Spt5 in vivo, we generated knock-out alleles for both genes in Drosophila melanogaster. Using the development of the mushroom bodies as a model, we provided evidence for two common functions of Spt4 and Spt5 during mushroom body development, namely control of cell proliferation of neural progenitor cells and remodeling of axonal projections of certain mushroom body neurons. This latter function is not due to a general requirement of Spt4 and Spt5 for axon pathfinding of mushroom body neurons, but due to distinct effects on the expression of genes controlling remodeling.

Single-cell somatic copy number variants in brain using different amplification methods and reference genomes

The presence of somatic mutations, including copy number variants (CNVs), in the brain is well recognized. Comprehensive study requires single-cell whole genome amplification, with several methods available, prior to sequencing. Here we compare PicoPLEX with two recent adaptations of multiple displacement amplification (MDA): primary template-directed amplification (PTA) and droplet MDA, across 93 human brain cortical nuclei. We demonstrate different properties for each, with PTA providing the broadest amplification, PicoPLEX the most even, and distinct chimeric profiles. Furthermore, we perform CNV calling on two brains with multiple system atrophy and one control brain using different reference genomes. We find that 20.6% of brain cells have at least one Mb-scale CNV, with some supported by bulk sequencing or single-cells from other brain regions. Our study highlights the importance of selecting whole genome amplification method and reference genome for CNV calling, while supporting the existence of somatic CNVs in healthy and diseased human brain.

Morphological and Metabolic Features of Brain Aging in Rodents, Ruminants, Carnivores, and Non-Human Primates

Brain aging in mammals is characterized by morphological and functional changes in neural cells. Macroscopically, this process, leading to progressive cerebral volume loss and functional decline, includes memory and motor neuron deficits, as well as behavioral disorders. Morphologically, brain aging is associated with aged neurons and astrocytes, appearing enlarged and flattened, and expressing enhanced pH-dependent β-galactosidase activity. Multiple mechanisms are considered hallmarks of cellular senescence in vitro, including cell cycle arrest, increased lysosomal activity, telomere shortening, oxidative stress, and DNA damage. The most common markers for senescence identification were identified in (i) proteins implicated in cell cycle arrest, such as p16, p21, and p53, (ii) increased lysosomal mass, and (iii) increased reactive oxygen species (ROS) and senescence-associated secretory phenotype (SASP) expression. Finally, dysfunctional autophagy, a process occurring during aging, contributes to altering brain homeostasis. The brains of mammals can be studied at cellular and subcellular levels to elucidate the mechanisms on the basis of age-related and degenerative disorders. The aim of this review is to summarize and update the most recent knowledge about brain aging through a comparative approach, where similarities and differences in some mammalian species are considered.

Exploring the reduction in aquaporin-4 and increased expression of ciliary neurotrophic factor with the frontal-striatal gliosis induced by chronic high-fat dietary stress.

High-fat diet (HFD)-induced obesity induces peripheral inflammation and hypothalamic pathogenesis linking the activation of astrocytes and microglia. Clinical evidence indicates a positive correlation between obesity and psychiatric disorders, such as depression. The connectivity of the frontal-striatal (FS) circuit, involving the caudate putamen (CPu) and anterior cingulate cortex (ACC) within the prefrontal cortex (PFC), is known for its role in stress-induced depression. Thus, there is a need for a thorough investigation into whether chronic obesity-induced gliosis, characterized by the activation of astrocytes and microglia, in these brain regions of individuals with chronic obesity. The results revealed increased S100β+ astrocytes and Iba1+ microglia in the CPu and ACC of male obese mice, along with immune cell accumulation in meningeal lymphatic drainage. Activated GFAP+ astrocytes and Iba1+ microglia were observed in the corpus callosum of obese mice. Gliosis in the CPu and ACC was linked to elevated cleaved caspase-3 levels, indicating potential neural cell death by chronic HFD feeding. There was a loss of myelin and adenomatous polyposis coli (APC)+ oligodendrocytes (OLs) in the corpus callosum, an area known to be linked with injury to the CPu. Additionally, reduced levels of aquaporin-4 (AQP4), a protein associated within the glymphatic systems, were noted in the CPu and ACC, while ciliary neurotrophic factor (CNTF) gene expression was upregulated in these brain regions of obese mice. The invitro study revealed thathigh-dose CNTF causing a trend of reduced astrocytic AQP4 expression, but it significantly impaired OL maturation. This pathological evidence highlights that prolonged HFD consumption induces persistent FS gliosis and demyelination in the corpus callosum. An elevated level of CNTF appears to act as a potential regulator, leading to AQP4 downregulation in the FS areas and demyelination in the corpus callosum. This cascade of events might contribute to neural cell damage within these regions and disrupt the glymphatic flow.

Restoring social deficits in IRSp53-deleted mice: chemogenetic inhibition of ventral dentate gyrus Emx1-expressing cells

IRSp53 is a synaptic scaffold protein reported to be involved in schizophrenia, autism spectrum disorders, and social deficits in knockout mice. Identifying critical brain regions and cells related to IRSp53 deletion is expected to be of great help in the treatment of psychiatric problems. In this study, we performed chemogenetic inhibition within the ventral dentate gyrus (vDG) of mice with IRSp53 deletion in Emx1-expressing cells (Emx1-Cre;IRSp53 flox/flox). We observed the recovery of social deficits after chemogenetic inhibition within vDG of Emx1-Cre;IRSp53 flox/flox mice. Additionally, chemogenetic activation induced social deficits in Emx1-Cre mice. CRHR1 expression increased in the hippocampus of Emx1-Cre;IRSp53 flox/flox mice, and CRHR1 was reduced by chemogenetic inhibition. Htd2, Ccn1, and Atp61l were decreased in bulk RNA sequencing, and Eya1 and Ecrg4 were decreased in single-cell RNA sequencing of the hippocampus in Emx1-Cre;IRSp53 flox/flox mice compared to control mice. This study determined that the vDG is a critical brain region for social deficits caused by IRSp53 deletion. Social deficits in Emx1-Cre;IRSp53 flox/flox mice were recovered through chemogenetic inhibition, providing clues for new treatment methods for psychiatric disorders accompanied by social deficits.

Adult Case of Pontocerebellar Hypoplasia without the Claustrum

We describe the case of a 63-year-old man with pontocerebellar hypoplasia without the claustrum (CL). The patient had a history of cerebral palsy, intelligent disability, cerebellar atrophy, and seizures since birth. At age 61, brain computed tomography (CT) revealed significant cerebellar and brainstem atrophy. At age 63, he was admitted to our hospital for aspiration pneumonia. Although he was treated with medications, including antibiotics, he died one month after admission. The autopsy revealed a total brain weight of 815 g, with the small-sized frontal lobe, cerebellum, and pons. The cross-section of the fourth ventricle had a slit-like appearance, rather than the typical diamond shape. In addition, bilateral CLs were not observed. Apart from CL, no other missing brain tissue or cells could be identified. Microscopic examinations disclosed neurofibrillary tangles in the hippocampus but not in the cortex; however, neither senile plaques nor Lewy bodies were detected. No acquired lesions, including cerebral infarction, hemorrhage, or necrosis, were noted. We pathologically diagnosed the patient with pontocerebellar hypoplasia without CL. As there have been no prior reports of pontocerebellar hypoplasia lacking CL in adults, this case may represent a new subtype. Congenital CL deficiency is likely associated with abnormalities in brain development. CL may play a role in seizure activity, and the loss of bilateral CLs does not necessarily result in immediate death. Further studies are needed to clarify the functions of CL.

Computational Fuzzy Modelling Approach to Analyze Neuronal Calcium Dynamics With Intracellular Fluxes.

Mathematical neuroscience investigates how calcium distribution in nerve cells affects the neurological system. The interaction of numerous systems is necessary for the operation of several cellular processes in neuron cells, such as calcium, buffer, ER etc. The dynamics of interacting parameters give useful information on neural cell function. This work uses a mathematical model to analyze the dynamic interactions of buffer and ER inside neurons, considering their spatial properties. While buffers bind to calcium ions and lower their concentration, the endoplasmic reticulum (ER) serves as a reservoir, holding a significant number of free calcium ions. The uncertainty of initial values of calcium concentration poses challenges for researchers to develop calcium signaling models. In this article, we examined the exact solution and approximate solution of the mathematical model that was analyzed using the fuzzy undetermined coefficient approach. MATLAB is being used to perform the simulation. Endoplasmic reticulum and buffer have been found to have a substantial impact on calcium signaling. Fuzzy differential equation Provides a useful tool for evaluating complicated processes with imprecise values when ordinary differential equations perform not precisely. They allow for the examination of dynamic processes under fuzzy settings, which contributes to advances research.

Calcium wave dynamics in the embryonic mouse gut mesenchyme: impact on smooth muscle differentiation

Intestinal smooth muscle differentiation is a complex physico-biological process involving several different pathways. Here, we investigate the properties of Ca2+ waves in the developing intestinal mesenchyme using GCamp6f expressing mouse embryos and investigate their relationship with smooth muscle differentiation. We find that Ca2+ waves are absent in the pre-differentiation mesenchyme and start propagating immediately following α-SMA expression. Ca2+ waves are abrogated by CaV1.2 and gap-junction blockers, but are independent of the Rho pathway. The myosine light-chain kinase inhibitor ML-7 strongly disorganized or abolished Ca2+ waves, showing that perturbation of the contractile machinery at the myosine level also affected the upstream Ca2+ handling chain. Inhibiting Ca2+ waves and contractility with CaV1.2 blockers did not perturb circular smooth muscle differentiation at early stages. At later stages, CaV1.2 blockers abolished intestinal elongation and differentiation of the longitudinal smooth muscle, leading instead to the emergence of KIT-expressing interstitial cells of Cajal at the gut periphery. CaV1.2 blockers also drove apoptosis of already differentiated, CaV1.2-expressing smooth muscle and enteric neural cells. We provide fundamental new data on Ca2+ waves in the developing murine gut and their relation to myogenesis in this organ.

Compensatory activity of the PC-ME1 metabolic axis underlies differential sensitivity to mitochondrial complex I inhibition.

Deficiencies in the electron transport chain (ETC) lead to mitochondrial diseases. While mutations are distributed across the organism, cell and tissue sensitivity to ETC disruption varies, and the molecular mechanisms underlying this variability remain poorly understood. Here we show that, upon ETC inhibition, a non-canonical tricarboxylic acid (TCA) cycle upregulates to maintain malate levels and concomitant production of NADPH. Our findings indicate that the adverse effects observed upon CI inhibition primarily stem from reduced NADPH levels, rather than ATP depletion. Furthermore, we find that Pyruvate carboxylase (PC) and ME1, the key mediators orchestrating this metabolic reprogramming, are selectively expressed in astrocytes compared to neurons and underlie their differential sensitivity to ETC inhibition. Augmenting ME1 levels in the brain alleviates neuroinflammation and corrects motor function and coordination in a preclinical mouse model of CI deficiency. These studies may explain why different brain cells vary in their sensitivity to ETC inhibition, which could impact mitochondrial disease management.

Role of Amniotic Fluid Toxicity in the Pathophysiology of Myelomeningocele: A Narrative Literature Review.

Myelomeningocele is a birth defect whose clinical manifestations are due both to incomplete neural tube closure and the progressive destruction of exposed neuroepithelium during pregnancy. Two hypotheses have been formulated to explain the spinal cord damage in utero: mechanical trauma and chemical factors. The objective of this review was to summarize the current insights about the potential role of amniotic fluid in spinal cord damage in myelomeningocele. Numerous histological and clinical data on animals and humans strongly suggest a progressive degeneration of neural tissue including loss of neural cells, astrogliosis, inflammation, and loss of normal architecture. However, few data have been published about the direct toxicity of amniotic fluid in this neural degeneration, including the potentially toxic effect of meconium. Finally, the chemical and cellular modifications of amniotic fluid composition in myelomeningocele could reflect both the process (toxic effect of meconium) and the consequences of neuroepithelium destruction (release of neural cells). Fetal surgery not only stops the leakage of the cerebrospinal fluid but also reduces the toxic effect of amniotic fluid by restoring the intrauterine environment. Identification of amniotic fluid neurotoxic factors could lead to the development of therapeutic agents designed to protect spinal tissue and improve fetal myelomeningocele outcomes.

Pemberdayaan Siswa-Siswi SMA Negeri 3 Kota Sibolga tentang Pelatihan Sederhana Bantuan Hidup Dasar (BHD) dalam Upaya Memberikan Pertolongan Pertama

Community service by the D-III Nursing Study Program in Central Tapanuli, Medan Ministry of Health Polytechnic, was carried out in the form of material presentations and demonstrations to students of SMA Negeri 3 Sibolga about Basic Life Support as first aid. Basic Life Support (BHD) is a series of first aid that is carried out to help anyone who experiences respiratory or cardiac arrest. One solution for first aid is to educate the public about Basic Life Support so that the possibility of brain cell damage will be smaller and give the victim enough time to be taken to the hospital on time. The target of service activities is 100 students of SMA Negeri 3 Sibolga. The aim of this Community Service is to realize community service as one of the Tri Darma activities of Higher Education, increasing the knowledge and skills of students in providing basic life support as emergency first aid. The methods used are counseling, training and question and answer/discussion and evaluation. After the counseling and demonstration of Basic Life Support was carried out, the results showed that the majority of respondents had sufficient knowledge at 58%, 35% had good knowledge and 7% had less knowledge. Competency evaluation is carried out by giving participants the opportunity to demonstrate directly the implementation of BHD using a phantom. The results obtained were that 63% had capable category skills and 37% had less capable skills, meaning that students still received assistance.