Maternal Leukemia Inhibitory Factor (LIF) Promotes Fetal Neurogenesis via a LIF-ACTH-LIF Signaling Relay Pathway

Leukemia inhibitory factor (LIF) promotes the proliferation of neuronal progenitor cells in the cerebrum. However, it remains unclear how fetal LIF level is regulated. Here we show evidence that maternal LIF signals drive fetal LIF levels via the placenta, thereby promoting neurogenesis in the fetal brain in rats. Chronological changes showed that LIF concentration in fetal sera (FS) and fetal cerebrospinal fluid peaked at gestational day (GD) 15.5, after the peak of maternal LIF at GD14.5. LIF injection into rat dams at GD15.5 increased the level of ACTH in FS and subsequently increased LIF levels in FS and fetal cerebrospinal fluid. The elevation of fetal LIF after LIF injection into dams was inhibited by in utero injection of anti-ACTH antibody into fetuses. Cultured syncytiotrophoblasts, which express the LIF receptor and glycoprotein 130, were induced to secrete ACTH and up-regulate Pomc expression by the addition of LIF. Nucleated red blood cells from fetuses at GD15.5, but not GD13.5 or GD17.5, displayed LIF secretion in response to ACTH. Moreover, injection of LIF into dams at GD13.5 or GD17.5 did not result in elevation of ACTH or LIF in fetuses. The labeling index of 5-bromo-2′-deoxyuridine-positive cells in the ventricular zone of the cerebral neocortex increased 24 h after injection of LIF into dams at GD15.5 but not GD13.5 or GD17.5. These results suggest that in rats maternal LIF induces ACTH from the placenta, which in turn induces fetal nucleated red blood cells to secrete LIF that finally increases neurogenesis in fetuses around GD15.

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Red blood cells in cerebrospinal fluid as possible inhibitory factor for enterovirus RT-PCR

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20160119 ◽

2016 ◽

Vol 74 (10) ◽

pp. 810-815 ◽

Cited By ~ 5

Author(s):

Sérgio Monteiro de Almeida ◽

Sônia Mara Raboni ◽

Meri Bordignon Nogueira ◽

Luine R. Renaud Vidal

Keyword(s):

Polymerase Chain Reaction ◽

Cerebrospinal Fluid ◽

Red Blood Cells ◽

Blood Cells ◽

Virus Detection ◽

Inhibitory Factor ◽

Rt Pcr ◽

Chain Reaction ◽

Negative Results ◽

Polymerase Chain

ABSTRACT The presence of hemoglobin in samples are considered an important inhibitory factor for polymerase chain reaction (PCR). The aim of this study was to examine the influence of red blood cells (RBC)s in cerebrospinal fluid (CSF) as an inhibitory factor to reverse transcription polymerase chain reaction (RT-PCR) for enteroviruses (EV). Forty-four CSF samples from patients showing characteristics of viral meningitis were assessed for EV by RT-PCR. Viral RNA extracted with guanidine isothyocianate buffer and virus detection was performed by in-house nested PCR. Positivity for EV RT-PCR was higher in CSF samples without RBCs than in samples with RBCs: 13(26%) and 36(9.2%), p = 0.001. In the group with positive EV RT-PCR, the mean + SD CSF RBC was 37 ± 183 cell/mm3; the group with negative results had 580 + 2,890 cell/mm3 (p = 0.007). The acceptable upper limit for CSF RBCs that could not influence RT-PCR was 108 cells/mm3. CSF samples with negative results for EV RT-PCR have more erythrocytes.

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Nucleated red blood cells in fetal brain injury show a consistent relationship with the intrapartum fhr pattern

American Journal of Obstetrics and Gynecology ◽

10.1016/j.ajog.2003.10.384 ◽

2003 ◽

Vol 189 (6) ◽

pp. S165 ◽

Cited By ~ 2

Author(s):

Jeffrey Phelan ◽

Cortney Kirkendall ◽

Lisa Korst ◽

Gilbert Martin

Keyword(s):

Brain Injury ◽

Red Blood Cells ◽

Blood Cells ◽

Fetal Brain ◽

Nucleated Red Blood Cells ◽

Consistent Relationship

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Nucleated red blood cells and hematological scoring system – Future trends in early onset neonatal sepsis

Medpusle International Journal of Pathology ◽

10.26611/10512112 ◽

2019 ◽

Vol 12 (1) ◽

pp. 53-58

Author(s):

Shivendra Vikram Singh ◽

◽

Megalamane Supreetha ◽

Satyavathi R Alva ◽

◽

...

Keyword(s):

Red Blood Cells ◽

Neonatal Sepsis ◽

Blood Cells ◽

Early Onset ◽

Scoring System ◽

Future Trends ◽

Nucleated Red Blood Cells

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Nucleated Red Blood Cells as Markers of Perinatal Adaptation in Preterm Neonates Receiving Minimally Invasive Surfactant Therapy

American Journal of Perinatology ◽

10.1055/s-0041-1726317 ◽

2021 ◽

Author(s):

Itamar Nitzan ◽

Calum T. Roberts ◽

Risha Bhatia ◽

Francis B. Mimouni ◽

Arvind Sehgal

Keyword(s):

Minimally Invasive ◽

Right Ventricular ◽

Red Blood Cells ◽

Blood Cells ◽

Surfactant Therapy ◽

Preterm Neonates ◽

Oxygen Requirement ◽

Nucleated Red Blood Cells ◽

Intrauterine Hypoxia ◽

Ventricular Ejection Time

Objective The study aimed to assess the association of nucleated red blood cells (NRBC), a surrogate of intrauterine hypoxia, and elevated pulmonic vascular resistance (E-PVR) and oxygen requirement after minimally invasive surfactant therapy (MIST). Study Design Retrospective study of a cohort of preterm neonates that received MIST in a single unit. Results NRBC were measured in 65 of 75 (87%) neonates administered MIST during the period. In total, 22 of 65 (34%) infants had pre-MIST echocardiography (ECHO).Neonates with elevated NRBC (predefined as >5 × 109/L, n = 16) required higher post-MIST fraction of inspired oxygen (FiO2) than neonates with normal NRBC (<1 × 109/L, n = 17; FiO2 = 0.31 ± 0.10 and 0.24 ± 0.04, respectively, p = 0.02).NRBC correlated positively with % of time in right to left ductal shunt (r = 0.51, p = 0.052) and inversely with right ventricular stroke volume (r = −0.55, p = 0.031) and time to peak velocity to right ventricular ejection time ratio (r = −0.62, p < 0.001). Conclusion Elevated NRBC are associated with elevated FiO2 after MIST and elevated E-PVR. Intrauterine hypoxia may impact postnatal circulatory adaptations and oxygen requirement. Key Points

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Nucleated red blood cells participate in myocardial regeneration in the toad Bufo Gargarizan Gargarizan

Experimental Biology and Medicine ◽

10.1177/15353702211013297 ◽

2021 ◽

pp. 153537022110132

Author(s):

Shu-Qin Liu ◽

Xiao-Ye Hou ◽

Feng Zhao ◽

Xiao-Ge Zhao

Keyword(s):

Red Blood Cells ◽

Blood Cells ◽

Cardiac Injury ◽

Myocardial Regeneration ◽

Matrix Metalloproteinase 2 ◽

Enzyme Linked Immunosorbent Assay ◽

Cardiac Tissues ◽

Nucleated Red Blood Cells ◽

Model Animal

Heart regeneration is negligible in humans and mammals but remarkable in some ectotherms. Humans and mammals lack nucleated red blood cells (NRBCs), while ectotherms have sufficient NRBCs. This study used Bufo gargarizan gargarizan, a Chinese toad subspecies, as a model animal to verify our hypothesis that NRBCs participate in myocardial regeneration. NRBC infiltration into myocardium was seen in the healthy toad hearts. Heart needle-injury was used as an enlarged model of physiological cardiomyocyte loss. It recovered quickly and scarlessly. NRBC infiltration increased during the recovery. Transwell assay was done to in vitro explore effects of myocardial injury on NRBCs. In the transwell system, NRBCs could infiltrate into cardiac pieces and could transdifferentiate toward cardiomyocytes. Heart apex cautery caused approximately 5% of the ventricle to be injured to varying degrees. In the mildly to moderately injured regions, NRBC infiltration increased and myocardial regeneration started soon after the inflammatory response; the severely damaged region underwent inflammation, scarring, and vascularity before NRBC infiltration and myocardial regeneration, and recovered scarlessly in four months. NRBCs were seen in the newly formed myocardium. Enzyme-linked immunosorbent assay and Western blotting showed that the levels of tumor necrosis factor-α, interleukin- 1β, 6, and11, cardiotrophin-1, vascular endothelial growth factor, erythropoietin, matrix metalloproteinase- 2 and 9 in the serum and/or cardiac tissues fluctuated in different patterns during the cardiac injury-regeneration. Cardiotrophin-1 could induce toad NRBC transdifferentiation toward cardiomyocytes in vitro. Taken together, the results suggest that the NRBC is a cell source for cardiomyocyte renewal/regeneration in the toad; cardiomyocyte loss triggers a series of biological processes, facilitating NRBC infiltration and transition to cardiomyocytes. This finding may guide a new direction for improving human myocardial regeneration.

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