Research Overview

Recipient of NIH Developmental Research Award (R21): 2023-2025
Project Title: Impact of Prolonged Perioperative Sedation on Infant Brain

Prolonged sedation treatment is currently considered standard practice in the safe and compassionate care of critically ill neonates and infants despite leading to opioid tolerance and a high incidence (35-57%) of physical dependence. There is a fundamental gap in our knowledge regarding (i) underlying mechanisms and (ii) long-term neurodevelopmental outcomes in selected group of infants born with esophageal atresia that undergo life-saving treatment with prolonged sedation. The study will employ structural MRI techniques (AIM 1) and neurodevelopmental assessment (AIM 2) in selected term-born and premature infants with short-gap (brief pain/sedation treatment) and long-gap esophageal atresia (prolonged sedation treatment).This study aligns with the goals of the National Institute of Child Health and Human Development (NICHD) and National Institute of Drug Abuse (NIDA) to improve the lives of children throughout all stages of development.

Recipient of NIH Mentored Clinical Scientist Development Award (K08): 2013-2018
Project Title: Immediate and Delayed Effects of Morphine on Brain Circuits: Animal - Human Correlation

Opioids are considered standard of care and used for management of acute pain, as well as for sedation of children of all ages. Our understanding of sequelae associated with prolonged opioid treatment on developing brain are limited. The is unique aspect of this project is in its translational effort to define the impact of prolonged morphine exposure in the rats of different ages using neuroimaging, behavioral, and immunohistochemical techniques (AIM 1), as well as in children of different ages using neuroimaging (AIM 2). Functional magnetic resonance imaging (fMRI) in both rats and children will allow a translational systems level investigation of prolonged morphine administration and its long-term effects. Dr. Bajic holds an academic title of Associated Professor of Anaesthesia at the Harvard Medical School since 2000.

Research Background

Dr. Bajic received her MD from the Medical School of the University of Belgrade, Serbia and PhD from the Department of Pharmacology at the University of Illinois at Chicago, IL. Her postdoctoral training included: (1) Postdoctoral Fellow at the Department of Anatomy and Cell Biology at the University of Illinois at Chicago, (2) Anesthesia Residency training at Yale New Haven Hospital, Yale University, as well as (3) Pediatric Anesthesia Fellowship at Children's Hospital Boston, Harvard University where she now works as board certified staff anesthesiologist since 2008.

Education

Medical School

University of Belgrade School of Medicine
1994 Belgrade Serbia

Graduate School

Pharmacology University of Illinois at Chicago
2000 Chicago IL

Residency

Anesthesia Yale New Haven Hospital
2007 New Haven CT

Fellowship

Pediatric Anesthesia Boston Children’s Hospital
2008 Boston MA

Publications

  1. Acute Dystonic Reaction After Propofol Administration: A Pediatric Case Report. A A Pract. 2023 Dec 01; 17(12):e01732. View Abstract
  2. Retrospective analysis of neurological findings in esophageal atresia: Allostatic load of disease complexity, cumulative sedation, and anesthesia exposure. Birth Defects Res. 2024 Jan; 116(1):e2269. View Abstract
  3. Body size and brain volumetry in the rat following prolonged morphine administration in infancy and adulthood. Front Pain Res (Lausanne). 2023; 4:962783. View Abstract
  4. Infant Perioperative Risk Factors and Adverse Brain Findings Following Long-Gap Esophageal Atresia Repair. J Clin Med. 2023 Feb 23; 12(5). View Abstract
  5. Two novel CHD7 variants in patients with typical and mild features of CHARGE syndrome co-occurring with esophageal atresia. J Pediatr Surg Case Rep. 2022; 87:102478. View Abstract
  6. MRI Atlas of the Infant Rat Brain: Brain Segmentation. 2022. View Abstract
  7. Impact of Infant Thoracic Non-cardiac Perioperative Critical Care on Homotopic-Like Corpus Callosum and Forebrain Sub-regional Volumes. Front Pain Res (Lausanne). 2022; 3:788903. View Abstract
  8. From the Ground Up: Esophageal Atresia Types, Disease Severity Stratification and Survival Rates at a Single Institution. Front Surg. 2022; 9:799052. View Abstract
  9. Infant study of hemispheric asymmetry after long-gap esophageal atresia repair. Ann Clin Transl Neurol. 2021 11; 8(11):2132-2145. View Abstract
  10. Head circumference in infants undergoing Foker process for long-gap esophageal atresia repair: Call for attention. J Pediatr Surg. 2021 Sep; 56(9):1564-1569. View Abstract
  11. Infant Corpus Callosum Size After Surgery and Critical Care for Long-Gap Esophageal Atresia: Qualitative and Quantitative MRI. Sci Rep. 2020 04 14; 10(1):6408. View Abstract
  12. Neurologic Injury and Brain Growth in the Setting of Long-Gap Esophageal Atresia Perioperative Critical Care: A Pilot Study. Brain Sci. 2019 Dec 17; 9(12). View Abstract
  13. Quantitative MRI study of infant regional brain size following surgery for long-gap esophageal atresia requiring prolonged critical care. Int J Dev Neurosci. 2019 Dec; 79:11-20. View Abstract
  14. Neonatal functional brain maturation in the context of perioperative critical care and pain management: A case report. Heliyon. 2019 Aug; 5(8):e02350. View Abstract
  15. Infant Brain Structural MRI Analysis in the Context of Thoracic Non-cardiac Surgery and Critical Care. Front Pediatr. 2019; 7:315. View Abstract
  16. Evaluation of Postnatal Sedation in Full-Term Infants. Brain Sci. 2019 May 17; 9(5). View Abstract
  17. Preoperative Evaluation of the Pediatric Patient. Anesthesiol Clin. 2018 Dec; 36(4):689-700. View Abstract
  18. Astrocytic hypertrophy in the rat ventral tegmental area following chronic morphine differs with age. J Neurol Neurorehabilit Res. 2018; 3(1):14-21. View Abstract
  19. Identifying Rodent Resting-State Brain Networks with Independent Component Analysis. Front Neurosci. 2017; 11:685. View Abstract
  20. Resting-State Functional Connectivity in the Infant Brain: Methods, Pitfalls, and Potentiality. Front Pediatr. 2017; 5:159. View Abstract
  21. Probing Intrinsic Resting-State Networks in the Infant Rat Brain. Front Behav Neurosci. 2016; 10:192. View Abstract
  22. Long-term behavioral effects in a rat model of prolonged postnatal morphine exposure. Behav Neurosci. 2015 Oct; 129(5):643-55. View Abstract
  23. Endogenous cholinergic neurotransmission contributes to behavioral sensitization to morphine. PLoS One. 2015; 10(2):e0117601. View Abstract
  24. In: Mattes K, Laubach A, Wang E, Anderson A. (Eds), Pediatric Anesthesiology Board Review. Plastic and Oral-Maxillary Facial Surgery. 2015. View Abstract
  25. Projections from the rat cuneiform nucleus to the A7, A6 (locus coeruleus), and A5 pontine noradrenergic cell groups. J Chem Neuroanat. 2013 May; 50-51:11-20. View Abstract
  26. Morphine-enhanced apoptosis in selective brain regions of neonatal rats. Int J Dev Neurosci. 2013 Jun; 31(4):258-66. View Abstract
  27. Periaqueductal gray neuroplasticity following chronic morphine varies with age: role of oxidative stress. Neuroscience. 2012 Dec 13; 226:165-77. View Abstract
  28. Ultrastructural analysis of rat ventrolateral periaqueductal gray projections to the A5 cell group. Neuroscience. 2012 Nov 08; 224:145-59. View Abstract
  29. Ketamine activates cell cycle signaling and apoptosis in the neonatal rat brain. Anesthesiology. 2010 May; 112(5):1155-63. View Abstract
  30. Acute noxious stimulation modifies morphine effect in serotonergic but not dopaminergic midbrain areas. Neuroscience. 2010 Mar 17; 166(2):720-9. View Abstract
  31. Visualizing acute pain-morphine interaction in descending monoamine nuclei with Fos. Brain Res. 2010 Jan 08; 1306:29-38. View Abstract
  32. Prolonged exposure to ketamine increases brain derived neurotrophic factor levels in developing rat brains. Curr Drug Saf. 2009 Jan; 4(1):11-6. View Abstract
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  41. Dissociated histaminergic neuron cultures from the tuberomammillary nucleus of rats: culture methods and ghrelin effects. J Neurosci Methods. 2004 Jan 30; 132(2):177-84. View Abstract
  42. Effects of orexin (hypocretin) on GIRK channels. J Neurophysiol. 2003 Aug; 90(2):693-702. View Abstract
  43. Two different inward rectifier K+ channels are effectors for transmitter-induced slow excitation in brain neurons. Proc Natl Acad Sci U S A. 2002 Oct 29; 99(22):14494-9. View Abstract
  44. Topographic architecture of stress-related pathways targeting the noradrenergic locus coeruleus. Physiol Behav. 2001 Jun; 73(3):273-83. View Abstract
  45. Ultrastructural analysis of ventrolateral periaqueductal gray projections to the A7 catecholamine cell group. Neuroscience. 2001; 104(1):181-97. View Abstract
  46. Periaqueductal gray neurons monosynaptically innervate extranuclear noradrenergic dendrites in the rat pericoerulear region. J Comp Neurol. 2000 Nov 27; 427(4):649-62. View Abstract
  47. Projections of neurons in the periaqueductal gray and cuneiform nucleus to pontine noradrenergic neurons [Ph.D. Thesis]; Chicago (IL): Univ. of Illinois at Chicago. pp.224. 2000. View Abstract
  48. Projections of neurons in the periaqueductal gray to pontine and medullary catecholamine cell groups involved in the modulation of nociception. J Comp Neurol. 1999 Mar 15; 405(3):359-79. View Abstract

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