Ricardo Ribeiro Nunes, Isadora D'Ávila Tassinari, Janaína Zang, Mirella Kielek Galvan Andrade, Anna Clara Machado Colucci, Mariana Leivas Müller Hoff, Maikel Rosa de Oliveira, Ana Helena Paz, Luciano Stürmer de Fraga
{"title":"Therapeutic Hypothermia Is Limited in Preventing Developmental Impairments after Neonatal Hypoxia-Ischemia.","authors":"Ricardo Ribeiro Nunes, Isadora D'Ávila Tassinari, Janaína Zang, Mirella Kielek Galvan Andrade, Anna Clara Machado Colucci, Mariana Leivas Müller Hoff, Maikel Rosa de Oliveira, Ana Helena Paz, Luciano Stürmer de Fraga","doi":"10.1159/000534919","DOIUrl":"10.1159/000534919","url":null,"abstract":"<p><p>The only current treatment for neonatal hypoxia-ischemia (HI) is therapeutic hypothermia (TH), which still shows some limitations. Specific effects of TH in the several processes involved in brain injury progression remain unclear. In this study, the effects of TH treatment on developmental parameters, behavioral outcomes, and peripheral leukocytes were evaluated in neonatal male and female rats. In P7, animals were submitted to right common carotid artery occlusion followed by hypoxia (8% oxygen). TH was performed by reducing the animal scalp temperature to 32°C for 5 h. Behavioral parameters and developmental landmarks were evaluated. Animals were euthanized at P9 or P21, and cerebral hemispheres, spleen, and thymus were weighed. White blood cells (WBCs) were counted in blood smears. There was a reduction in the weight of the brain hemisphere ipsilateral to the carotid occlusion in HI and TH groups, as well as a reduction in body weight gain and a delay in the opening of the ipsilateral eye. Latency in negative geotaxis was increased by HI at P12. TH did not prevent brain weight loss, developmental impairments, or WBC number changes but prevented negative geotaxis impairment and spleen weight reduction. These data reinforce that a better understanding of the events that occur after HI and TH in both males and females is necessary and would allow the development of more adequate and sex-specific therapeutic approaches.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"273-284"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71428704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shah Rukh, Daniel W Meechan, Thomas M Maynard, Anthony-Samuel Lamantia
{"title":"Out of Line or Altered States? Neural Progenitors as a Target in a Polygenic Neurodevelopmental Disorder.","authors":"Shah Rukh, Daniel W Meechan, Thomas M Maynard, Anthony-Samuel Lamantia","doi":"10.1159/000530898","DOIUrl":"10.1159/000530898","url":null,"abstract":"<p><p>The genesis of a mature complement of neurons is thought to require, at least in part, precursor cell lineages in which neural progenitors have distinct identities recognized by exclusive expression of one or a few molecular markers. Nevertheless, limited progenitor types distinguished by specific markers and lineal progression through such subclasses cannot easily yield the magnitude of neuronal diversity in most regions of the nervous system. The late Verne Caviness, to whom this edition of Developmental Neuroscience is dedicated, recognized this mismatch. In his pioneering work on the histogenesis of the cerebral cortex, he acknowledged the additional flexibility required to generate multiple classes of cortical projection and interneurons. This flexibility may be accomplished by establishing cell states in which levels rather than binary expression or repression of individual genes vary across each progenitor's shared transcriptome. Such states may reflect local, stochastic signaling via soluble factors or coincidence of cell surface ligand/receptor pairs in subsets of neighboring progenitors. This probabilistic, rather than determined, signaling could modify transcription levels via multiple pathways within an apparently uniform population of progenitors. Progenitor states, therefore, rather than lineal relationships between types may underlie the generation of neuronal diversity in most regions of the nervous system. Moreover, mechanisms that influence variation required for flexible progenitor states may be targets for pathological changes in a broad range of neurodevelopmental disorders, especially those with polygenic origins.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-21"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9876672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R Ann Sheldon, Christine Windsor, Fuxin Lu, Nicholas R Stewart, Xiangning Jiang, Donna M Ferriero
{"title":"Hypothermia Treatment after Hypoxia-Ischemia in Glutathione Peroxidase-1 Overexpressing Mice.","authors":"R Ann Sheldon, Christine Windsor, Fuxin Lu, Nicholas R Stewart, Xiangning Jiang, Donna M Ferriero","doi":"10.1159/000531204","DOIUrl":"10.1159/000531204","url":null,"abstract":"<p><p>The developing brain is uniquely susceptible to oxidative stress, and endogenous antioxidant mechanisms are not sufficient to prevent injury from a hypoxic-ischemic challenge. Glutathione peroxidase (GPX1) activity reduces hypoxic-ischemic injury. Therapeutic hypothermia (HT) also reduces hypoxic-ischemic injury, in the rodent and the human brain, but the benefit is limited. Here, we combined GPX1 overexpression with HT in a P9 mouse model of hypoxia-ischemia (HI) to test the effectiveness of both treatments together. Histological analysis showed that wild-type (WT) mice with HT were less injured than WT with normothermia. In the GPX1-tg mice, however, despite a lower median score in the HT-treated mice, there was no significant difference between HT and normothermia. GPX1 protein expression was higher in the cortex of all transgenic groups at 30 min and 24 h, as well as in WT 30 min after HI, with and without HT. GPX1 was higher in the hippocampus of all transgenic groups and WT with HI and normothermia, at 24 h, but not at 30 min. Spectrin 150 was higher in all groups with HI, while spectrin 120 was higher in HI groups only at 24 h. There was reduced ERK1/2 activation in both WT and GPX1-tg HI at 30 min. Thus, with a relatively moderate insult, we see a benefit with cooling in the WT but not the GPX1-tg mouse brain. The fact that we see no benefit with increased GPx1 here in the P9 model (unlike in the P7 model) may indicate that oxidative stress in these older mice is elevated to an extent that increased GPx1 is insufficient for reducing injury. The lack of benefit of overexpressing GPX1 in conjunction with HT after HI indicates that pathways triggered by GPX1 overexpression may interfere with the neuroprotective mechanisms provided by HT.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"98-111"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10667569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10156194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Antoine Giraud, Pauline Garel, Brian H Walsh, Stéphane Chabrier
{"title":"From Early Motor Ability to Global Cognitive Development 7 Years after Neonatal Arterial Ischemic Stroke.","authors":"Antoine Giraud, Pauline Garel, Brian H Walsh, Stéphane Chabrier","doi":"10.1159/000533816","DOIUrl":"10.1159/000533816","url":null,"abstract":"<p><p>The developmental condition of children after neonatal arterial ischemic stroke (NAIS) is characterized by cognitive and motor impairments. We hypothesized that independent walking age would be a predictor of later global cognitive functioning in this population. Sixty-one children with an available independent walking age and full-scale intelligence quotient (IQ) score 7 years after NAIS were included in this study. Full-scale IQ was assessed using the fourth edition of the Wechsler Intelligence Scale for Children (WISC-IV). Independent walking age was negatively correlated with full-scale IQ score at 7 years of age (Pearson correlation coefficient of -0.27; 95% confidence interval from -0.48 to -0.01; p < 0.05). Early motor function is correlated with later global cognitive functioning in children after NAIS. Assessing and promoting early motor ability is essential in this population.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"149-152"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11151956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10476395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Beyond the Rainbow: A Review of Advanced Lineage Tracing Methodologies for Interrogating the Initiation, Evolution, and Recurrence of Brain Tumors","authors":"Sara Sabet, Joshua J. Breunig","doi":"10.1159/000530329","DOIUrl":"https://doi.org/10.1159/000530329","url":null,"abstract":"The mammalian forebrain is perhaps the pinnacle of evolution and one of the most complex structures in known existence. The origin of this complexity and diversity partly lies in dynamic behavior of progenitors during embryonic neural development, all of which is under the control of regulatory mechanisms that ensure all the elements end up in the right place at the right time. Historically, dye-base, histochemical, enzymatic, or fluorescent lineage tracing techniques have been used deconvolute developmental dynamics in tissues and cells. Technical limitations resulted from a restrictive number of fluorophores, the half-life of the dyes, or the ability to deconvolute mixed population. These limitations often impede larger scale lineage tracing using these methods in spatial and temporal contexts. Genetic barcoding techniques have been used for decades to explore clonal investigations and have now evolved with high-throughput sequencing methods to allow for impressive insights into population and even organism-level lineage relationships. In this review, we will discuss the progression of lineage tracing methodologies and how they are applied to answer questions around molecular and cellular mechanisms of gliogenesis and neurogenesis. We will also discuss recent advances in computational biology, single-cell sequencing, and in situ-based lineage tracing methodologies. Incorporation of these methods into toolset of lineage tracing promise to enable a higher resolution, multimodal view of neural lineages during development and disease processes that highjack developmental signaling such as brain tumor development and recurrence – where traditional developmental hierarchies become more plastic and less predictable. Given the dismal prognosis of high-grade brain tumors like glioblastoma multiforme, a better understanding of the lineage relationships leading to disease heterogeneity and recurrence is desperately needed to formulate efficacious approaches to treatment. Here we discuss a historical foundation on, as well as the future of, lineage tracing at the intersection of development and disease.","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":"45 1","pages":"181 - 190"},"PeriodicalIF":2.9,"publicationDate":"2023-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49022988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}