Behavioral and neuroanatomical outcomes following altered serotonin expression in a hypoxic-ischemic injury neonate rodent model

BACKGROUND: Children born prematurely (<37 gestational weeks) are at risk for a variety of adverse medical events. They may experience ischemic and/or hemorrhagic events leading to negative neural sequelae. They are also exposed to repeated stressful experiences as part of life-saving care within the neonatal intensive care unit (NICU). These experiences have been associated with methylation of SLC6A4, a gene which codes for serotonin transport proteins, and is associated with anxiety, depression, and increased incidence of autism spectrum disorders. The purpose of this study was to examine the effects of altered serotonin levels on behavioral and neuroanatomical outcomes in a neonatal rodent model with or without exposure to hypoxic-ischemic (HI) injury. METHODS: Wistar rat pups were randomly assigned to either HI injury or sham groups. Pups within each group were treated with a chronic SSRI (Citalopram HBr) to simulate the effects of SLC6A4 methylation, or saline (NS). Subjects were assessed on behavioral tasks and neuropathologic indices. RESULTS: HI injured subjects performed poorly on behavioral tasks. SSRI subjects did not display significantly greater anxiety. HI + SSRI subjects learned faster than HI+NS. Histologically, SSRI subjects had predominantly larger brain volumes than NS. CONCLUSION: SSRI treated subjects without injury showed patterns of increased anxiety, consistent with theories of SLC6A4 methylation. The paradoxical trend to improved cognition in HI+SSRI subjects relative to HI alone, may reflect an unexpected SSRI neuroprotective effect in the presence of injury, and may be related to serotonin-induced neurogenesis.

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CORM-3 exerts a neuroprotective effect in a rodent model of traumatic brain injury via the bidirectional gut–brain interactions

Experimental Neurology ◽

10.1016/j.expneurol.2021.113683 ◽

2021 ◽

pp. 113683

Author(s):

Li-Min Zhang ◽

Dong-Xue Zhang ◽

Wei-Chao Zheng ◽

Jin-Shu Hu ◽

Lan Fu ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Neuroprotective Effect ◽

Rodent Model ◽

Brain Interactions

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Isolation-induced vocalization in wistar rat pups is not increased by naltrexone

Physiology & Behavior ◽

10.1016/0031-9384(91)90363-s ◽

1991 ◽

Vol 49 (6) ◽

pp. 1279-1282 ◽

Cited By ~ 15

Author(s):

S.E. Carden ◽

M.A. Hofer

Keyword(s):

Wistar Rat ◽

Rat Pups

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Experimental neonatal hypoxia ischemia causes long lasting changes of oxidative stress parameters in the hippocampus and the spleen

Journal of Perinatal Medicine ◽

10.1515/jpm-2017-0070 ◽

2018 ◽

Vol 46 (4) ◽

pp. 433-439 ◽

Cited By ~ 8

Author(s):

Felipe Kawa Odorcyk ◽

Janaína Kolling ◽

Eduardo Farias Sanches ◽

Angela T.S. Wyse ◽

Carlos Alexandre Netto

Keyword(s):

Oxidative Stress ◽

Wistar Rat ◽

Mortality And Morbidity ◽

Neonatal Hypoxia ◽

Oxidative Stress Parameters ◽

Rat Pups ◽

Hypoxia Ischemia ◽

Anti Oxidant ◽

Enzyme Superoxide Dismutase ◽

Stress Parameters

Abstract Neonatal hypoxia ischemia (HI) is the main cause of mortality and morbidity in newborns. The mechanisms involved in its progression start immediately and persist for several days. Oxidative stress and inflammation are determinant factors of the severity of the final lesion. The spleen plays a major part in the inflammatory response to HI. This study assessed the temporal progression of HI-induced alterations in oxidative stress parameters in the hippocampus, the most affected brain structure, and in the spleen. HI was induced in Wistar rat pups in post-natal day 7. Production of reactive oxygen species (ROS), and the activity of the anti oxidant enzyme superoxide dismutase and catalase were assessed 24 h, 96 h and 38 days post-HI. Interestingly, both structures showed a similar pattern, with few alterations in the production of ROS species up to 96 h often combined with an increased activity of the anti oxidant enzymes. However, 38 days after the injury, ROS were at the highest in both structures, coupled with a decrease in the activity of the enzymes. Altogether, present results suggest that HI causes long lasting alterations in the hippocampus as well as in the spleen, suggesting a possible target for delayed treatments for HI.

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A Child has a Right to Blood Transfusion Services in Nigeria, despite the Religious Status of the Parents or Guardians

Annals of Bioethics & Clinical Applications ◽

10.23880/abca-16000207 ◽

2021 ◽

Vol 4 (4) ◽

Author(s):

Uchejeso M Obeta

Keyword(s):

Intensive Care ◽

Blood Transfusion ◽

Blood Cell ◽

Neonatal Intensive Care ◽

Healthcare Providers ◽

Red Blood Cell Transfusion ◽

Blood Transfusions ◽

Blood Products ◽

Serious Illness ◽

Life Saving

Red blood cell transfusion is an important and frequent component of neonatal intensive care. Whereas blood and blood products transfusion can help a patient (child) recover from a serious illness, surgery or injury, because of the religious beliefs of some parents or guardians, a child may be denied the benefit of this life-saving service. Several legal statutes and precedents exist to protect the rights of children in need of life-saving blood transfusions where denied this opportunity to be transfused and survive. The awareness of these extant laws and statutes are critical for the empowerment of healthcare providers in the performance of their role within the provisions of the law and medical ethics.

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Screening for Autism Spectrum Disorder in Premature Subjects Hospitalized in a Neonatal Intensive Care Unit

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17207675 ◽

2020 ◽

Vol 17 (20) ◽

pp. 7675

Author(s):

Norrara Scarlytt de Oliveira Holanda ◽

Lidiane Delgado Oliveira da Costa ◽

Sabrinne Suelen Santos Sampaio ◽

Gentil Gomes da Fonseca Filho ◽

Ruth Batista Bezerra ◽

...

Keyword(s):

Intensive Care Unit ◽

Autism Spectrum Disorder ◽

Intensive Care ◽

Neonatal Intensive Care Unit ◽

Neonatal Intensive Care ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Screening Methods ◽

Early Signs ◽

Type Of Delivery

Considering that the average age for diagnosis of autism spectrum disorder (ASD) is 4–5 years, testing screening methods for ASD risk in early infancy is a public health priority. This study aims to identify the risks for development of ASD in children born prematurely and hospitalized in a neonatal intensive care unit (NICU) and explore the association with pre-, peri- and postnatal factors. Methods: The children’s families were contacted by telephone when their child was between 18 and 24 months of age, to apply the Modified Checklist for Autism in Toddlers (M-CHAT). The sample consisted of 40 children (57.5% boys). M-CHAT screening revealed that 50% of the sample showed early signs of ASD. Although the frequency of delayed development was higher in boys, this difference was not statistically significant between the sexes (p = 0.11). Assessment of the association between perinatal conditions and early signs of autism in children hospitalized in an NICU exhibited no correlation between the factors analyzed (birth weight and type of delivery). The findings indicate a high risk of ASD in premature children, demonstrating no associations with gestational and neonatal variables or the hospitalization conditions of the NICUs investigated.

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Effect of hyperbaric oxygen on apoptosis in neonatal hypoxia-ischemia rat model

Journal of Applied Physiology ◽

10.1152/japplphysiol.00630.2003 ◽

2003 ◽

Vol 95 (5) ◽

pp. 2072-2080 ◽

Cited By ~ 59

Author(s):

John W. Calvert ◽

Changman Zhou ◽

Anil Nanda ◽

John H. Zhang

Keyword(s):

Hyperbaric Oxygen ◽

Caspase 3 ◽

Apoptotic Cell ◽

Neuroprotective Effect ◽

Parp Cleavage ◽

Artery Ligation ◽

Neonatal Hypoxia ◽

Rat Pups ◽

Hypoxia Ischemia ◽

Expression And Activity

We have previously demonstrated that a transient exposure to hyperbaric oxygen (HBO) attenuated the neuronal injury after neonatal hypoxia-ischemia. This study was undertaken to determine whether HBO offers this neuroprotection by reducing apoptosis in injured brain tissue. Seven-day-old rat pups were subjected to unilateral carotid artery ligation followed by 2 h of hypoxia (8% oxygen). Apoptotic cell death was examined in the injured cortex and hippocampus tissue. Caspase-3 expression and activity increased at 18 and 24 h after the hypoxia-ischemia insult. At 18-48 h, poly(ADP-ribose) polymerase (PARP) cleavage occurred, which reduced the band at 116 kDa and enhanced the band at 85 kDa. There was a time-dependent increase in the number of terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL)-positive cells. A single HBO treatment (100% oxygen, 3 ATA for 1 h) 1 h after hypoxia reduced the enhanced caspase-3 expression and activity, attenuated the PARP cleavage, and decreased the number of TUNEL-positive cells observed in the cortex and hippocampus. These results suggest that the neuroprotective effect of HBO is at least partially mediated by the reduction of apoptosis.

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