Evidence map›Paper›PMID 24361177›Full record

ArticleNeuroscience2014

Sexual dimorphism in BDNF signaling after neonatal hypoxia-ischemia and treatment with necrostatin-1.

R Chavez-Valdez, L J Martin, S Razdan, E B Gauda, F J Northington

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
5.9field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

R Chavez-ValdezDepartment of Pediatrics, Neonatal Research Laboratory, Johns Hopkins University School of Medicine, 600 North Wolfe Street, CMSC 6-104, Baltimore, MD 21287, USA. Electronic address: rchavez2@jhmi.edu.
L J MartinDepartment of Pathology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross Research Building, Room 558, Baltimore, MD 21205, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross Research Building, Room 558, Baltimore, MD 21205, USA.
S RazdanDepartment of Pediatrics, Neonatal Research Laboratory, Johns Hopkins University School of Medicine, 600 North Wolfe Street, CMSC 6-104, Baltimore, MD 21287, USA.
E B GaudaDepartment of Pediatrics, Neonatal Research Laboratory, Johns Hopkins University School of Medicine, 600 North Wolfe Street, CMSC 6-104, Baltimore, MD 21287, USA.
F J NorthingtonDepartment of Pediatrics, Neonatal Research Laboratory, Johns Hopkins University School of Medicine, 600 North Wolfe Street, CMSC 6-104, Baltimore, MD 21287, USA.
Johns Hopkins University · US

Funding

Mechanisms of Hypothermic Neuroprotection in NeonatesR01HD070996 · NICHD · JOHNS HOPKINS UNIVERSITY · PI NORTHINGTON, FRANCES J · 2012 to 2016
$1.7M
NICHD NIH HHS R01 HD070996NICHD NIH HHS R01HD070996
6 · The paper itself

Abstract

Brain injury due to neonatal hypoxia-ischemia (HI) is more homogenously severe in male than in female mice. Because, necrostatin-1 (nec-1) prevents injury progression only in male mice, we hypothesized that changes in brain-derived neurotrophic factor (BDNF) signaling after HI and nec-1 are also sex-specific providing differential conditions to promote recovery of those more severely injured. The increased aromatization of testosterone in male mice during early development and the link between 17-β-estradiol (E2) levels and BDNF transcription substantiate this hypothesis. Hence, we aimed to investigate if sexual differences in BDNF signaling existed in forebrain and diencephalon after HI and HI/nec-1 and their correlation with estrogen receptors (ER). C57B6 mice (p7) received nec-1 (0.1μl [8μM]) or vehicle (veh) intracerebroventricularly after HI. At 24h after HI, BDNF levels increased in both sexes in forebrain without evidence of tropomyosin-receptor-kinase B (TrkB) activation. At 96h after HI, BDNF levels in forebrain decreased below those seen in control mice of both sexes. Additionally, only in female mice, truncated TrkB (Tc.TrkB) and p75 neurotrophic receptor (p75ntr) levels increased in forebrain and diencephalon. In both, forebrain and diencephalon, nec-1 treatment increased BDNF levels and TrkB activation in male mice while, nec-1 prevented Tc.TrkB and p75ntr increases in female mice. While E2 levels were unchanged by HI or HI/nec-1 in either sex or treatment, ERα:ERβ ratios were increased in diencephalon of nec-1-treated male mice and directly correlated with BDNF levels. Neonatal HI produces sex-specific signaling changes in the BDNF system, that are differentially modulated by nec-1. The regional differences in BDNF levels may be a consequence of injury severity after HI, but sexual differences in response to nec-1 after HI may represent a differential thalamo-cortical preservation or alternatively off-target regional effect of nec-1. The biological significance of ERα predominance and its correlation with BDNF levels is still unclear.

Indexed as

AnimalsAnimals, NewbornBrain-Derived Neurotrophic FactorDiencephalonEstradiolFemaleHypoxia-Ischemia, BrainImidazolesIndolesMaleMiceMice, Inbred C57BLNeuroprotective AgentsParvalbuminsProsencephalonReceptors, EstrogenBrain-Derived Neurotrophic FactorEstradiolImidazolesIndolesnecrostatin-1Neuroprotective AgentsParvalbuminsReceptors, Estrogenanalysis of varianceANOVABDNFbrain-derived neurotrophic factorcortexE2ELISAenzyme-linked immunosorbent assayEREREestradiolestrogen receptorestrogen response elementFL.TrkBfull-length TrkBHIhypoxia–ischemianec-1necrostatin-1ODoptical densitypp75 neurotrophic receptorp75ntrphosphorylated TrkBplasticitypost-natal daypTrkBqRT-PCRquantitative reverse transcriptase polymerase chain reactionTc.TrkBthalamusTrkBtropomyosin-receptor-kinase Btruncated TrkBtruncated TrkB receptorvehvehicle

Identifiers

PMID24361177
PMCPMC3950408
OpenAlexW1983352454

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.