Methadone alters the peripheral inflammatory and central immune landscape following prenatal exposure in rats.

Autor:	Madurai NK; Division of Neonatal-Perinatal Medicine, Department of Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, MD, United States., Kitase Y; Division of Neonatal-Perinatal Medicine, Department of Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, MD, United States., Hamimi S; Division of Neonatal-Perinatal Medicine, Department of Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, MD, United States.; Division of Pediatric Neurosurgery, Department of Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, MD, United States., Kirk SE; Division of Neonatal-Perinatal Medicine, Department of Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, MD, United States., Sevensky R; Division of Neonatal-Perinatal Medicine, Department of Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, MD, United States., Ramachandra S; Division of Neonatal-Perinatal Medicine, Department of Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, MD, United States., Muthukumar S; Division of Pediatric Neurosurgery, Department of Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, MD, United States., Vasan V; Division of Pediatric Neurosurgery, Department of Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, MD, United States., Ozen M; Division of Neonatal-Perinatal Medicine, Department of Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, MD, United States., Gerner G; Department of Neuropsychology, Kennedy Krieger Institute, Baltimore, MD, United States.; Department of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, United States., Robinson S; Division of Pediatric Neurosurgery, Department of Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, MD, United States., Jantzie LL; Division of Neonatal-Perinatal Medicine, Department of Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, MD, United States.; Division of Pediatric Neurosurgery, Department of Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, MD, United States.; Department of Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore, MD, United States.; Department of Neurology, School of Medicine, Johns Hopkins University, Baltimore, MD, United States.
Jazyk:	angličtina
Zdroj:	Advances in drug and alcohol research [Adv Drug Alcohol Res] 2022; Vol. 2. Date of Electronic Publication: 2022 Nov 29.
DOI:	10.3389/adar.2022.10792
Abstrakt:	Opioid use during pregnancy continues to rise at alarming rates with a parallel trend in the number of infants and children exposed to opioid medications each year. Prenatal opioid exposure (POE) occurs at a critical timepoint in neurodevelopment disrupting intricate pathways essential for neural-immune maturation with the potential for devastating long-term consequences. Understanding the mechanisms underlying injury associated with POE is essential to address long-term outcomes and identify diagnostic and therapeutic biomarkers in this vulnerable patient population. Using an established preclinical model of POE, we investigated changes in cerebral and peripheral inflammation and peripheral blood mononuclear cell (PBMC) activity. We hypothesized that neuroinflammation, as defined by changes in specific cerebral immune cell populations, would exist in adult rats following POE concomitant with sustained peripheral immune hyperreactivity (SPIHR). Our data demonstrated alterations in cerebral immune cells at postnatal day 60 (P60) typified by increased regulatory T cells ( p < 0.01) and neutrophils ( p < 0.05) in rats with POE compared to controls. Evaluation of serum revealed increased levels of IL-6 ( p < 0.05) and CXCL1 ( p < 0.05) at P21 in rats with POE compared to controls with no significant difference in cytokine or chemokine levels between the two groups at P60. Additionally, PBMCs isolated from rats with POE at P21 demonstrated baseline hypersecretion of IL-6 ( p < 0.01) and SPIHR with increased levels of TNF-α ( p < 0.05) and CXCL1 ( p < 0.05) following stimulation with LPS. At P60, however, there was no significant difference found in cytokine or chemokine levels secreted by PBMCs isolated from rats with POE at baseline or with LPS stimulation when compared to controls. Taken together, these data demonstrate cerebral inflammation months after prenatal opioid exposure and long after the resolution of systemic inflammation and SPIHR seen at toddler age equivalent. Chronic alterations in the cerebral immune cell populations secondary to prenatal opioid exposure may underly long-term consequences of developmental brain injury including deficits in cognition and attention. These findings may be invaluable to further investigations of precise biomarkers of injury and targeted therapeutics for this vulnerable population. Competing Interests: Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Databáze:	MEDLINE
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