Safety of Continuous Erector Spinae Catheters in Chest Trauma: A Retrospective Cohort Study.

BACKGROUND: The erector spinae block is an efficacious analgesic option for the management of rib fracture--related pain. Despite there being minimal published data specifically addressing the safety profile of this block, many societies have made statements regarding its safety and its use as an alternative to traditional regional anesthesia techniques in patients at risk of complications. The primary aim of this study was to characterize the safety profile of erector spinae plane block catheters by determining the incidence of early complications. The secondary aim of this study was to characterize the incidence of late adverse events, as well as the erector spinae plane block catheter failure rate. METHODS: We analyzed electronic medical record data of patients who had an erector spinae plane block catheter inserted for the management of rib fractures between November 2017 and September 2020. To assess early adverse events, data collection included hypotension, hypoxemia, local anesthetic systemic toxicity, and pneumothorax thought to be associated with erector spinae plane block catheter insertion. Late complications included catheter site infection and catheter site hematoma. RESULTS: A total of 224 patients received 244 continuous erector spinae catheters during the study period. After insertion of the erector spinae, there were no immediate complications such as hypotension, hypoxia, local anesthetic toxicity, or pneumothorax. Of all blocks inserted, 7.7% were removed due to catheter failure (8.4 per 100 catheters; 95% confidence interval [CI], 5.1-13.9 per 100 catheters). This resulted in a failure rate of 1.9 per 1000 catheter days (95% CI, 1.1-6.7 catheter days). Late complications included 2 erythematous catheter sites and 2 small hematomas not requiring intervention. The incidence of a minor late complication was 16.7 per 1000 catheters (95% CI, 6.1-45.5 per 1000 catheters). CONCLUSIONS: This study supports the statements made by regional anesthesia societies regarding the safety of the erector spinae plane block. Based on the results presented in this population of trauma patients, the erector spinae plane block catheter is a low-risk analgesic technique that may be performed in the presence of abnormal coagulation status or systemic infection.

Induction opioids for caesarean section under general anaesthesia: a systematic review and meta-analysis of randomised controlled trials.

INTRODUCTION: The adverse effects of induction opioids on the neonate are poorly characterised. The study aim was to investigate whether induction opioids can be used in caesarean section without adversely affecting the neonate. METHODS: Six databases were systematically searched from inception until January 2019. Included studies compared induction opioids and placebo in caesarean section. Results were presented as odds ratios (95% confidence intervals) for dichotomous outcomes and weighted mean difference for continuous outcomes. An I2 statistic of >50% was significant for heterogeneity. The primary outcome was Apgar score (1 and 5 min). Secondary outcomes included neonatal adverse events, cord blood gas analyses, maternal haemodynamic parameters (systolic blood pressure (SBP), mean arterial pressure (MAP), heart rate (HR) and catecholamine concentrations. RESULTS: Seventeen studies (n=987) were included in the meta-analysis. Remifentanil 0.5-1 µg/kg or 2-3 µg/kg/h, alfentanil 7.5-10 µg/kg and fentanyl 0.5-1 µg/kg were compared to placebo. There was no significant difference in Apgar scores at 1 min (P=0.25, 0.58 and 0.89 respectively) for all three opioids or at 5 min for remifentanil and alfentanil (P=0.08 and 0.21 respectively). Fentanyl significantly reduced 5 min Apgar scores (P=0.002). There was no difference in neonatal airway interventions with remifentanil or alfentanil (P <0.05). All three induction opioids caused a significant reduction in maximum SBP (P <0.0001), MAP (P <0.00001) and HR (P <0.00001). CONCLUSION: Induction opioids are effective sympatholytic agents. Remifentanil and alfentanil appear to be safe, with no significant effect on Apgar scores or neonatal airway intervention, but a well-powered trial is required to confirm these findings.

Land-Atmosphere Responses to a Total Solar Eclipse in Three Ecosystems With Contrasting Structure and Physiology.

Mid-Missouri experienced up to 2 min 40 s of totality at around solar noon during the total eclipse of 2017. We conducted the Mid-Missouri Eclipse Meteorology Experiment to examine land-atmosphere interactions during the eclipse. Here, research examining the eclipse responses in three contrasting ecosystems (forest, prairie, and soybeans) is described. There was variable cloudiness around first and fourth contacts (i.e., the start and end of partial solar obscuration) at the forest and prairie; however, solar irradiance (K ↓) signals during the eclipse were relatively clean. Unfortunately, the eclipse forcing at the soybean field was contaminated by convective activity, which decreased K ↓ beginning about an hour before first contact and exposed the field to cold outflow ~30 min before second contact. Turbulence was suppressed during the eclipse at all sites; however, there was also an amplified signal at the soybean field during the passage of a gust front. The standard deviations of the horizontal and vertical wind velocities and friction velocities decreased by ~75% at the forest (aerodynamically rough), and ~60% at the prairie (aerodynamically smooth). The eddy fluxes of energy were highly coherent with the solar forcing with the latent and sensible heat fluxes approaching 0 W/m2 and changing in direction, respectively. For the prairie site, we estimated a canopy-scale time constant for the surface conductance light response of 10 min. Although the eclipse imparted large forcings on surface energy balances, the air temperature response was relatively muted (1.5-2.5 °C decrease) due to the absence of topographic effects and the relatively moist land and atmosphere.

Quantifying the dark data in museum fossil collections as palaeontology undergoes a second digital revolution.

Large-scale analysis of the fossil record requires aggregation of palaeontological data from individual fossil localities. Prior to computers, these synoptic datasets were compiled by hand, a laborious undertaking that took years of effort and forced palaeontologists to make difficult choices about what types of data to tabulate. The advent of desktop computers ushered in palaeontology's first digital revolution-online literature-based databases, such as the Paleobiology Database (PBDB). However, the published literature represents only a small proportion of the palaeontological data housed in museum collections. Although this issue has long been appreciated, the magnitude, and thus potential significance, of these so-called 'dark data' has been difficult to determine. Here, in the early phases of a second digital revolution in palaeontology--the digitization of museum collections-we provide an estimate of the magnitude of palaeontology's dark data. Digitization of our nine institutions' holdings of Cenozoic marine invertebrate collections from California, Oregon and Washington in the USA reveals that they represent 23 times the number of unique localities than are currently available in the PBDB. These data, and the vast quantity of similarly untapped dark data in other museum collections, will, when digitally mobilized, enhance palaeontologists' ability to make inferences about the patterns and processes of past evolutionary and ecological changes.

Efficacy and adverse effects of buprenorphine in acute pain management: systematic review and meta-analysis of randomised controlled trials.

Buprenorphine appears to have a ceiling effect on respiratory depression, but not analgesia in healthy young patients. However, the efficacy and side-effects of buprenorphine in the setting of acute pain are poorly characterized. The aim of this study was to characterize the analgesic efficacy and adverse effects of buprenorphine compared with morphine in the acute pain setting. A systematic review of five databases was performed. Randomised controlled trials (RCTs) comparing buprenorphine with morphine in acute pain management were included. Studies performed outside of the hospital setting were excluded. The a priori primary outcomes included pain, respiratory depression, and sedation. Secondary outcomes included requirement for rescue analgesia, time to rescue analgesia, nausea, vomiting, dizziness, hypotension, and pruritus. Twenty-eight RCTs with 2210 patients met the inclusion criteria. There was no difference in pain [visual analogue scale weighted mean difference (WMD)=-0.29; 95% confidence interval (CI)=-0.62 to 0.03; I2=99%; P=0.07], incidence of respiratory depression [odds ratio (OR)=2.07; 95% CI=0.78-5.51; I2=30%; P=0.14], or sedation (OR=1.44; 95% CI=0.76-2.74; I2=23%; P=0.26). There was only one secondary outcome with an overall significant difference; buprenorphine use was associated with significantly less pruritus (OR=0.31; 95% CI=0.12-0.84; I2=6%; P=0.02). Whilst a theoretical ceiling effect may exist with respect to buprenorphine and respiratory depression, in a clinical setting, it can still cause significant adverse effects on respiratory function. However, given that buprenorphine is an equally efficacious analgesic agent, it is a useful alternative opioid because of its ease of administration and reduced incidence of pruritus.

Apnoeic oxygenation during intubation: a systematic review and meta-analysis.

Apnoeic oxygenation during intubation is used to prevent desaturation during intubation. The aim of this review was to assess whether apnoeic oxygenation during endotracheal intubation reduced the incidence of hypoxaemia. Five major databases were systematically searched for all relevant studies published up to May 2016. All study designs with a control group and a group receiving apnoeic oxygenation were included in this review. These studies were then assessed for level of evidence and risk of bias. The data were then analysed using a meta-analysis. Eleven studies (six high quality randomised controlled trials, four low quality level two studies and one low quality level three study) were found. In the meta-analysis there was strong evidence for benefit of apnoeic oxygenation in terms of improved SpO2 in elective surgical patients, obese patients and those undergoing emergency intubation without respiratory failure. However, no significant benefit was found in patients with respiratory failure. This is the first meta-analysis to be performed on apnoeic oxygenation during intubation. Apnoeic oxygenation provides significant benefit in terms of improving SpO2 for the majority of intubations, although there appears to be no benefit in patients whose indication for intubation is respiratory failure. Apnoeic oxygenation ought to be considered for integration into intubation protocols.

Molecular and functional characteristics of ovarian surface epithelial cells transformed by KrasG12D and loss of Pten in a mouse model in vivo.

Ovarian cancer is a complex and deadly disease that remains difficult to detect at an early curable stage. Furthermore, although some oncogenic (Kras, Pten/PI3K and Trp53) pathways that are frequently mutated, deleted or amplified in ovarian cancer are known, how these pathways initiate and drive specific morphological phenotypes and tumor outcomes remain unclear. We recently generated Pten(fl/fl); Kras(G12D); Amhr2-Cre mice to disrupt the Pten gene and express a stable mutant form of Kras(G12D) in ovarian surface epithelial (OSE) cells. On the basis of histopathologic criteria, the mutant mice developed low-grade ovarian serous papillary adenocarcinomas at an early age and with 100% penetrance. This highly reproducible phenotype provides the first mouse model in which to study this ovarian cancer subtype. OSE cells isolated from ovaries of mutant mice at 5 and 10 weeks of age exhibit temporal changes in the expression of specific Mullerian epithelial marker genes, grow in soft agar and develop ectopic invasive tumors in recipient mice, indicating that the cells are transformed. Gene profiling identified specific mRNAs and microRNAs differentially expressed in purified OSE cells derived from tumors of the mutant mice compared with wild-type OSE cells. Mapping of transcripts or genes between the mouse OSE mutant data sets, the Kras signature from human cancer cell lines and the human ovarian tumor array data sets, documented significant overlap, indicating that KRAS is a key driver of OSE transformation in this context. Two key hallmarks of the mutant OSE cells in these mice are the elevated expression of the tumor-suppressor Trp53 (p53) and its microRNA target, miR-34a-c. We propose that elevated TRP53 and miR-34a-c may exert negatively regulatory effects that reduce the proliferative potential of OSE cells leading to the low-grade serous adenocarcinoma phenotype.

New and evolving concepts in the neurotoxicology of lead.

Lead (Pb) is a xenobiotic metal with no known essential function in cellular growth, proliferation, or signaling. Decades of research characterizing the toxicology of Pb have shown it to be a potent neurotoxicant, especially during nervous system development. New concepts in the neurotoxicology of Pb include advances in understanding the mechanisms and cellular specificity of Pb. Experimental studies have shown that stress can significantly alter the effects of Pb, effects that could potentially be mediated through alterations in the interactions of glucocorticoids with the mesocorticolimbic dopamine system of the brain. Elevated stress, with corresponding elevated glucocorticoid levels, has been postulated to contribute to the increased levels of many diseases and dysfunctions in low socioeconomic status populations. Cellular models of learning and memory have been utilized to investigate the potential mechanisms of Pb-induced cognitive deficits. Examination of long-term potentiation in the rodent hippocampus has revealed Pb-induced increases in threshold, decreases in magnitude, and shorter retention times of synaptic plasticity. Structural plasticity in the form of adult neurogenesis in the hippocampus is also impacted by Pb exposure. The action of Pb on glutamate release, NMDA receptor function, or structural plasticity may underlie perturbations in synaptic plasticity and contribute to learning impairments. In addition to providing insight into potential mechanisms of Pb-induced cognitive deficits, cellular models offer an opportunity to investigate direct effects of Pb on isolated biological substrates. A target of interest is the 78-kDa molecular chaperone glucose-regulated protein (GRP78). GRP78 chaperones the secretion of the cytokine interleukin-6 (IL-6) by astrocytes. In vitro evidence shows that Pb strongly binds to GRP78, induces GRP78 aggregation, and blocks IL-6 secretion in astroglial cells. These findings provide evidence for a significant chaperone deficiency in Pb-exposed astrocytes in culture. In the long term, chaperone deficiency could underlie protein conformational diseases such as Alzheimer's Disease (AD). Lead exposure in early life has been implicated in subsequent progression of amyloidogenesis in rodents during old age. This exposure resulted in an increase in proteins associated with AD pathology viz., beta-amyloid precursor protein (beta-APP), and beta-amyloid (Abeta). These four new lines of research comprise compelling evidence that exposures to Pb have adverse effects on the nervous system, that environmental factors increase nervous system susceptibility to Pb, and that exposures in early life may cause neurodegeneration in later life.

Comparative genomic hybridisation using a proximal 17p BAC/PAC array detects rearrangements responsible for four genomic disorders.

BACKGROUND: Proximal chromosome 17p is a region rich in low copy repeats (LCRs) and prone to chromosomal rearrangements. Four genomic disorders map within the interval 17p11-p12: Charcot-Marie-Tooth disease type 1A, hereditary neuropathy with liability to pressure palsies, Smith-Magenis syndrome, and dup(17)(p11.2p11.2) syndrome. While 80-90% or more of the rearrangements resulting in each disorder are recurrent, several non-recurrent deletions or duplications of varying sizes within proximal 17p also have been characterised using fluorescence in situ hybridisation (FISH). METHODS: A BAC/PAC array based comparative genomic hybridisation (array-CGH) method was tested for its ability to detect these genomic dosage differences and map breakpoints in 25 patients with recurrent and non-recurrent rearrangements. RESULTS: Array-CGH detected the dosage imbalances resulting from either deletion or duplication in all the samples examined. The array-CGH approach, in combination with a dependent statistical inference method, mapped 45/46 (97.8%) of the analysed breakpoints to within one overlapping BAC/PAC clone, compared with determinations done independently by FISH. Several clones within the array that contained large LCRs did not have an adverse effect on the interpretation of the array-CGH data. CONCLUSIONS: Array-CGH is an accurate and sensitive method for detecting genomic dosage differences and identifying rearrangement breakpoints, even in LCR-rich regions of the genome.

Qualitative and quantitative estimates of apoptosis from birth to senescence in the rat brain.

Apoptosis is crucial for proper development of the CNS, wherein a significant percentage of all central neurons produced during early ontogeny die by apoptosis. To characterize the pattern of developmental programmed cell death, we assayed rat brainstem, neocortex, hippocampus, and cerebellum from birth through senescence. Quantitatively, using an ELISA for oligonucleosomal DNA fragments, we demonstrated that PND1 brainstem, neocortex, and hippocampus have the highest levels of fragmented DNA compared to older ages. Cerebellum displayed a large peak at PND10 and a smaller peak at PND21. Low levels were observed throughout adulthood and into senescence, which was corroborated qualitatively by agarose gel and TUNEL data. These data provide a temporal and regional baseline for further studies of the effects of perturbations of cell death during neural development. Quantitative and qualitative changes in these regional profiles of apoptosis due to environmental insults during early ontogeny may alter neuron number and function later in life.

vvd is required for light adaptation of conidiation-specific genes of Neurospora crassa, but not circadian conidiation.

con-10 and con-6 are two of the conidiation (con) genes of Neurospora crassa that were identified based on their preferential expression during macroconidiophore development. They are also regulated by several other environmental stimuli independent of development, including a transient induction by light. We identified an allele of vivid (vvd) in a mutant screen designed to obtain strains with altered expression of con-10. vvd mutants display enhanced carotenoid pigmentation in response to light. In addition, con-10 and con-6 show a heightened response to photoinduction. We tested the function of the light-responsive circadian clock in the vvd mutant and found no major defect in the circadian rhythm of conidiation or light regulation of a key clock component, frequency (frq). We conclude that vvd is primarily involved in a process of light-dependent gene repression, called light adaptation. Although a number of gene products are known to control light induction in fungi, vvd is the first gene shown to have a role in adaptation to constant light.

Differential patterns of nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 mRNA and protein levels in developing regions of rat brain.

The present studies were undertaken to characterize the regional and temporal patterns of neurotrophin messenger RNA and protein levels for beta-nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 in the developing CNS. We have examined the levels of these neurotrophin messenger RNAs with ribonuclease protection assays and corresponding protein levels with enzyme-linked immunosorbent assays in the developing Long-Evans rat hippocampus, neocortex and cerebellum on postnatal days 1, 7, 14, 21, and 92. In addition, immunohistochemistry was used to localize the neurotrophins in these developing brain regions. Results indicated that in neocortex and hippocampus, messenger RNA for both nerve growth factor and brain-derived neurotrophic factor increased in an age-dependent manner, reaching a plateau by postnatal day 14. In the neocortex, nerve growth factor and brain-derived neurotrophic factor protein levels both peaked at postnatal day 14. In hippocampus, nerve growth factor protein peaked at postnatal day 7 while brain-derived neurotrophic factor peaked at postnatal day 14. In cerebellum, nerve growth factor messenger RNA levels were flat, while nerve growth factor protein peaked at postnatal day 7. Brain-derived neurotrophic factor messenger RNA increased in an age-dependent manner while the pattern for its protein levels was mixed. Neurotrophin-3 messeger RNA levels increased in an age-dependent manner in hippocampus, peaked at postnatal day14 in cerebellum, and no changes occurred in neocortex. Neurotrophin-3 protein was at its peak at postnatal day 1 and thereafter decreased at other postnatal days in all three brain regions. Results of neurotrophin immunohistochemistry often paralleled and complemented enzyme-linked immunosorbent assay data, demonstrating specific cell groups containing neurotrophin proteins in these regions. Within each region, patterns with regard to messenger RNA and respective protein levels for each neurotrophin were unique. No consistent relationship between patterns of neurotrophin messenger RNAs and their cognate proteins was observed between regions. The different regional patterns for neurotrophin messengerRNA and protein levels in each brain region indicate that messenger RNA studies of neurotrophin messenger RNA must be augmented by protein determination to fully characterize spatial and temporal neurotrophin distribution.

Vulnerable processes of nervous system development: a review of markers and methods.

The susceptibility of the developing nervous system to damage following exposure to environmental contaminants has been well recognized. More recently, from a regulatory perspective, an increased emphasis has been placed on the vulnerability of the developing nervous system to damage following pesticide exposure. The publication of the National Academy of Sciences (NAS) report on Pesticides in the Diets of Infants and Children (1995) and the passage of the Food Quality Protection Act (FQPA) and Safe Drinking Water Act (SDWA) amendments have significantly escalated the scientific debate regarding age-related susceptibility. Key concerns raised in the NAS report include the qualitative and quantitative differences that distinguish the developing nervous system from that of the adult. It was suggested that neurotoxicity testing on adult animals alone may not be predictive of these differences in susceptibility. The age-related susceptibility of the nervous system is compounded by the protracted period of time over which this complex organ system develops. This temporal vulnerability spans the embryonic, fetal, infant, and adolescent periods. Normal development of the nervous system requires the concomitant and coordinated ontogeny of proliferation, migration, differentiation, synaptogenesis, gliogenesis, myelination and apoptosis to occur in a temporally- and regionally-dependent manner. Perturbations of these processes during development can result in long-term irreversible consequences that affect the structure and function of the nervous system and could account for qualitative differences in age-related susceptibility of the developing nervous system as compared to the adult nervous system. A discussion of developmental milestones and the relevance of transient effects on developmental endpoints are presented. Transient effects following developmental perturbations can be missed or dismissed depending on the experimental design or screening strategy employed. This subject is discussed in light of scientific uncertainties regarding perturbation-induced compensation in the developing nervous system. Thus, utilization of age-appropriate tests of these developmental processes may improve the detection and reduce uncertainty about the nature of adverse effects following developmental exposure to environmental neurotoxicants.

Effects of chronic prenatal hypoxia on tyrosine hydroxylase and phenylethanolamine N-methyltransferase messenger RNA and protein levels in medulla oblongata of postnatal rat.

Catecholamines are a class of neurotransmitters involved in central nervous system autonomic control. Both acute and chronic hypoxia create alterations in ventilation and blood pressure via catecholamine release, although the mechanisms of these alterations are unknown. The enzymes tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) catalyze the rate-limiting step in the catecholamine pathway and production of epinephrine, respectively. Both have been colocalized with Fos protein in metabolic mapping studies of the O2-chemosensory pathway of adult and early postnatal rat. Thus, catecholamines are putative neurotransmitters in a subset of second and higher order respiratory neurons. To characterize the effects of prenatal hypoxia on subsequent TH and PNMT gene and protein expression, pregnant rats were placed in moderate hypoxia (10% O2) from gestational d 18 until birth. Northern and Western analyses of dorsal (catecholaminergic/adrenergic cell group 2) and ventral (catecholaminergic/adrenergic cell group 1) medullary tissue of postnatal (P) age P0, P3, P7, P10, and P14 pups were then done to examine changes in TH and PNMT mRNA and protein compared with normoxia-reared controls. Compared with controls, pups exposed to maternal hypoxia during pregnancy had lower levels of TH mRNA and protein at birth in dorsal medulla and higher levels of TH mRNA the first postnatal week in the ventral medulla. Pups that had been hypoxic in utero showed significantly lower levels of PNMT protein during the second postnatal week in dorsal medulla than did controls. Prenatal hypoxia-induced changes in levels of enzymes responsible for catecholamine synthesis may later be manifest as developmental deficiencies in neuronal function. This may compromise responses to acute hypoxic challenges during early postnatal life and contribute to autonomic nervous system disorders of the newborn such as apnea and sudden infant death syndrome.

Insertion of the retroposable element, jockey, near the Adh gene of Drosophila melanogaster is associated with altered gene expression.

The alcohol dehydrogenase (Adh) gene of Drosophila melanogaster is well suited to be a gene expression reporter system. Adh produces a measurable phenotype at both the enzyme and mRNA levels. We recovered a spontaneous transposable element (TE) insertion mutation near the Adh gene. The insertion is a truncated retroposable element, jockey, inserted upstream of the adult Adh enhancer region. Comparisons between the Adhjockey allele and its direct wild-type ancestral allele were made in an isogenic background (i.e. identical cis and trans factors). Differences in Adhjockey expression compared with the wild-type can be attributed solely to the presence of the jockey element. This jockey insertion results in a decrease in adult mRNA transcript levels in the Adhjockey homozygous lines relative to the wild-type counterpart and accounts for a correlated decrease in alcohol dehydrogenase (ADH) enzyme activity. The larval ADH activity levels are not detectably different.

An eye color gene for the detection of transgenic non-drosophilid insects.

A genetic marker for identifying transgenic Musca domestica by changes in eye color is described. The Drosophila melanogaster tryptophan oxygenase gene, vermilion (v), was tested for its ability to genetically complement the mutant tryptophan oxygenase gene in houseflies homozygous for green (ge). The v cDNA, placed under the control of the hsp82 promoter of D. pseudoobscura was transiently expressed in M. domestica embryos homozygous for the tryptophan oxygenase gene, ge, resulting in the rescue of adult eye color. The use of a gene from D. melanogaster to complement an eye color mutant in Musca provides the opportunity to develop a gene vector system for M. domestica and a select group of other non-drosophilid insects in which homologous mutations exist.

Molecular analysis of a spontaneous insertion mutation near the alcohol dehydrogenase gene of Drosophila melanogaster.

The structural integrity of the Adh gene in several isogenic lines of Drosophila melanogaster was tested by Southern blot analysis using a 4.75 kilobase (kb) genomic clone of Alcohol dehydrogenase (Adh) as a probe. One line, RI22, III, showed evidence of a spontaneous insertion mutation 5' to the adult enhancer in an area previously indicated as a putative larval enhancer region. The inserted allele was present at an approximate frequency of 50% in relation to the uninserted wildtype allele. Isogenic lines were constructed of both homozygous mutant and wildtype flies, allowing the comparison of a spontaneous insertion mutant allele and it's direct wildtype ancestral allele. The inserted sequence is a 296 basepair (bp) truncated jockey retroposable element. The sequence and distribution of the element as well as it's proximity to the Adh gene are discussed.

Ontogeny of the O2-sensitive pathway in medulla oblongata of postnatal rat.

Fos protein, the product of the immediate early gene c-fos, has been used as a metabolic marker to map the O2 chemosensory pathway activated by hypoxia in the adult rat (Erickson and Millhorn, Brain Res. 567: 11-24, 1991). The current study provides evidence that the O2 chemoreceptor pathway develops during the first postnatal month. Rats at postnatal ages (P) 3, 7, 10, 14, 21, and 28 days were exposed for 3 h to 21% (control) or 10% (hypoxia) O2. Pups were transcardially fixed, brain stems were frozen, sectioned, then reacted with Fos primary antibody, a secondary antibody, avidin-biotin peroxidase, then Ni-DAB as chromogen. Cells showing Fos-like immunoreactivity (Fos-LI) under control and hypoxic conditions were counted in the nucleus tractus solitarii (NTS) and the ventrolateral medulla (VLM). In both areas there was initially a low basal level of Fos-LI, a peak at P10 and a decline to P28. At all ages there was a significant increase in the number of Fos-LI cells in pups exposed to hypoxia. The high basal level of Fos expression at P10 and the high induced level at P14 may correlate with periods of terminal differentiation and maximum synaptogenesis, respectively.