Tag Archive for: Kratimenos

The endovascular embolic hemispherectomy team.

New hemimegalencephaly procedure is all about teamwork

Children’s National experts pioneered a novel approach of inducing strokes to stop seizures and improve neurodevelopmental outcomes in newborns under three months old with hemimegalencephaly (HME). The procedure, called an endovascular embolic hemispherectomy, can be safely used to provide definitive treatment of HME-related epilepsy in neonates and young infants. Monica Pearl, M.D., neurointerventional radiologist, and Panagiotis Kratimenos, M.D., Ph.D., neonatologist, discuss why having a multidisciplinary team skilled at this procedure is the reason we’re the only center in the world capable of providing this treatment.

Dr. Panagiotis Kratimenos in the lab

Understanding mechanisms of injury due to prematurity in human cerebellum

Dr. Panagiotis Kratimenos in the lab

“There is no better model to study preterm injury than the human brain. Our team, along with the expertise of the scientific advisory board of the Raynor Cerebellum Project, will approach this project in multiple ways to extract the most possible information from the extremely precious human tissues,” says Dr. Kratimenos.

Children’s National Hospital has received $1 million in funding as part of the Raynor Cerebellum Project, whose mission is to improve the lives of those with cerebellar disease in seven to ten years. Panagiotis Kratimenos, M.D., Ph.D., principal investigator and Co-Director of Research in the Division of Neonatology at Children’s National, says the goal of this work is to understand the mechanisms of injury due to prematurity in human cerebellum and identify opportunities for intervention.

Why the research is unique

This project is unique because it focuses on postmortem human cerebellum, addressing the effect of the immune dysregulation of the mother during preterm labor. “We have established a large cohort of human term and preterm subjects and we will leverage cutting edge techniques to understand how the immune system of the mother during preterm labor shapes the cerebellum in a way that becomes more vulnerable to subsequent insults,” says Dr. Kratimenos.

Why this research matters for critical newborns

“There is no better model to study preterm injury than the human brain. Our team, along with the expertise of the scientific advisory board of the Raynor Cerebellum Project, will approach this project in multiple ways to extract the most possible information from the extremely precious human tissues. This will give us insight into the real mechanisms of preterm birth induced injury due to maternal immune dysregulation,” says Dr. Kratimenos.

newborn in incubator

Neuroprotective effect of Src kinase in neonates affected by HIE

newborn in incubator

Hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal morbidity and mortality worldwide.

In a systematic review published by Frontiers in Neuroscience, and co-authored by Panagiotis Kratimenos, M.D., neonatologist at Children’s National Hospital, Ioannis Koutroulis, M.D., pediatric emergency medicine physician at Children’s National and Javid Ghaemmaghami, M.S., researcher with the Center for Neuroscience Research at Children’s National, it was concluded that Src kinase is an effective neuroprotective target in the setting of acute hypoxic injury.

The paper reviews hypoxic-ischemic encephalopathy (HIE), a major cause of neonatal morbidity and mortality worldwide (one in four perinatal deaths is attributed to hypoxic-ischemic). While therapeutic hypothermia has improved neurodevelopmental outcomes for some survivors of HIE, this treatment is only available to a subset of affected neonates. Src kinase, an enzyme central to the apoptotic cascade, is a potential pharmacologic target to preserve typical brain development after HIE. This paper, a product of collaboration for a Master’s Thesis with the Aristotle University School of Medicine, Thessaloniki, Greece, where Dr. Kratimenos holds the appointment of Visiting  Professor,  presents evidence of the neuroprotective effects of targeting Src kinase in preclinical models of HIE.

The systematic review shows that while heterogeneity and risk for bias were limiting factors, the overall results indicate that Src-i neuroprotective properties could be a promising therapeutic strategy for neonates after hypoxic events.

Read more about the full review.

illustration of a brain

Inducing strokes in newborns to treat hemimegalencephaly

“The number one thing people are perplexed by is how well these babies recover and how they can only live with half a brain,” said Tayyba Anwar, M.D., neonatal neurologist and co-director of the Hemimegalencephaly Program at Children’s National Hospital. “People think if a child has half a brain that’s damaged or dysplastic, how are they functioning? But babies are so resilient. It still amazes me.”

The big picture

Children’s National experts have pioneered a novel approach of inducing strokes to stop seizures and improve neurodevelopmental outcomes in newborns under three months old with hemimegalencephaly (HME).

The procedure, called an endovascular embolic hemispherectomy, can be safely used to provide definitive treatment of HME-related epilepsy in neonates and young infants, according to a study in the Journal of NeuroInterventional Surgery.

Prior to this approach, the standard treatment was an anatomic hemispherectomy — surgical removal of the affected half of the brain. But infants had to be at least three months old to undergo such a complex surgery. Delaying surgery meant the persistent seizures compromised the development of the healthy half of the brain.

What they’re saying

In this video, Dr. Anwar and Panagiotis Kratimenos, M.D., Ph.D., neonatologist and co-director of Research in Neonatology at Children’s National, discuss the critically important neonatal care provided to babies who undergo endovascular embolic hemispherectomy and how protocols have evolved with each case to make this less invasive approach a feasible early alternative to surgical hemispherectomy.

Drs. Anwar and Kratimenos are part of the multidisciplinary team of neonatal neurologists, neurointerventional radiologists, neonatologists and neurosurgeons performing endovascular hemispherectomies.

Brain illustration

Paving the way toward better understanding and treatment of neonatal brain injuries

Brain illustration

The Gallo Lab’s latest research finds reduced expression of Sirt2 in the white matter of premature human infants and characterizes its role in white matter of the brain in normal conditions and during hypoxia.

Changes in myelination due to diffuse white matter injury are a common consequence of premature birth and hypoxic-ischemic injury due to asphyxia of sick term-born newborns. Hypoxic damage during the neonatal period can lead to motor disabilities and cognitive deficits with long-term consequences, including cerebral palsy, intellectual disability or epilepsy, which are often due to cellular and functional abnormalities.

The Gallo Lab, within the Center for Neuroscience Research at Children’s National Hospital, is focused on studying postnatal neural development and the impact of injury and disease on development and regeneration of neurons and glia. Their latest research, published in Nature Communications, finds reduced expression of Sirt2 in the white matter of premature human infants (born earlier than 32 weeks of gestation) and characterizes its role in white matter of the brain in normal conditions as well as during hypoxia.

What it means

The lab previously identified Sirt1 as important for the proliferative regenerative response of oligodendrocyte progenitor cells in response to chronic neonatal hypoxia. This new study characterizes the function of Sirt2 and finds that it acts as a critical promoter of oligodendrocyte differentiation during both normal brain development and after hypoxia.

It’s likely this reduced expression of Sirt2 contributes to the arrest in oligodendrocyte maturation and myelination failure seen in extremely low gestational age neonates. Therefore, targeting Sirt2 may be an opportunity to capture the early and small window of opportunity for therapeutic intervention.

How this moves the field forward

Sirtuins have been shown to play crucial therapeutic roles in various diseases, including aging, neurodegenerative disorders, cardiovascular disease and cancer. Identifying Sirt2 as a major regulator of white matter development and recovery and increasing the understanding of its protein and genomic interactions opens new avenues for Sirt2 as a therapeutic target for white matter injury in premature babies.

Why we’re excited

Interestingly, the team found that overexpression of Sirt2 in oligodendrocyte progenitor cells, but not mature oligodendrocytes, restores oligodendrocyte populations after hypoxia through enhanced proliferation and protection from apoptosis. This is exciting because:

  • It tells us that Sirt2 expression is very important for the transition from progenitor to differentiated oligodendrocyte.
  • It’s the first report, to the team’s knowledge, of Sirt2 regulating cell survival of oligodendrocytes.

Read more in Nature Communications

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Children’s National Hospital at the 2022 Pediatric Academic Societies Meeting

Are you attending the 2022 Pediatric Academic Societies meeting this week? There will be over 20 Children’s National Hospital-affiliated participants at this year’s meeting. We have compiled their sessions into a mini schedule below.

Name Department Role Topic Date Time
Kristen Sgambat, Ph.D., R.D. Center for Translational Research Speaker Fueling our patients for success: Optimizing nutritional support for kids with kidney disease 4/22/2022 2:30 PM
Priti Bhansali, M.D., M.Ed. Child Health Advocacy Institute Co-speaker APA Division Directors/Faculty Development Combined SIG 4/23/2022 8:00 AM
Karen Smith, M.D., M.Ed.
Neha Shah, M.D., M.P.H.		 Workshop co-leaders Don’t Struggle In Solitude: Recovery and Peer Support after Unanticipated Outcomes, Errors, and Difficult Conversations 4/23/2022 8:00 AM
Ian Chua, M.D., M.H.P.E.
Gabrina Dixon, M.D., M.Ed.
Margarita Ramos, M.D., M.S.		 Workshop co-leaders Finding the DEI in LGBTQIA: Incorporating LGBTQIA diversity in your environment 4/23/2022 8:00 AM
Kevin M. Cook, Ph.D. Co-presenter Early exposure to the extra-uterine environment in premature infants is associated with altered functional brain connectivity compared to in-utero age-matched fetuses 4/23/2022 8:15 AM
Gabrina Dixon, M.D., M.Ed.
Terry Kind, M.D., M.P.H.		 Workshop co-leaders Changing the system: Best practices in supporting and advancing underrepresented in medicine (UIM) medical students 4/23/2022 10:00 AM
Yao Wu, Ph.D. Oral abstract presenter Impaired prenatal brain growth predicts adverse neurodevelopmental outcomes in infants with congenital heart disease 4/23/2022 10:00 AM
Lee S. Beers, M.D. General and Community Pediatrics Moderator Scholarship in the Domain of Child Health Advocacy: Making It Work in the Academic Medical Center 4/23/2022 10:00 AM
Chaya Merrill, Dr.P.H. Center for Translational Research Speaker Using data to advance advocacy in the academic medical center 4/23/2022 10:00 AM
Yuan-Chiao Lu, Ph.D. Oral abstract presenter Delayed Fetal Cortical Maturation Predicts 18-Month Neurodevelopment in Infants with Congenital Heart Disease 4/23/2022 10:15 AM
Olanrewaju O. Falusi, M.D., M.Ed. Child Health Advocacy Institute Speaker Generating currency for advancement and professional development in the domain of advocacy 4/23/2022 10:15 AM
Subechhya Pradhan, Ph.D. Oral abstract presenter Abnormal in-vivo brain biochemistry in fetuses with complex congenital heart disease 4/23/2022 10:30 AM
Lenore R. Jarvis, M.D., M.Ed. Emergency Medicine and Trauma Services Speaker Academic advocacy for the subspecialist 4/23/2022 10:30 AM
Jillian E. Nickerson, M.D., M.S. Emergency Medicine and Trauma Services Presenter Utilizing an Online Module Platform to Teach Newborn Delivery and Resuscitation Skills to Pediatric Emergency Medicine Providers 4/23/2022 10:30 AM
Lee S. Beers, M.D. General and Community Pediatrics Presenting Author Leadership in legislative advocacy at the national level 4/23/2022 11:00 AM
Kevin M. Cook, Ph.D. Oral abstract presenter Relative neighborhood disadvantage is associated with increased functional network segregation in fetal brains 4/23/2022 11:15 AM
Jung-Hoon Kim, Ph.D. Presenting Author Gestational age-related changes in the fetal functional connectome: in utero evidence for the global signal 4/23/2022 1:00 PM
Ioannis Koutroulis, M.D., Ph.D., M.B.A. Emergency Medicine and Trauma Services Oral abstract presenter Immunometabolism in septic encephalopathy: a novel therapeutic target 4/23/2022 1:00 PM
Terry Kind, M.D., M.P.H. General and Community Pediatrics Workshop co-leaders Making Meaning from the Data: Exploring Coding in Qualitative Research 4/23/2022 1:00 PM
Josepheen D. Cruz, M.D., Ph.D. Oral abstract presenter Cortical thickness changes in fetuses exposed to heightened maternal psychological distress 4/23/2022 1:30 PM
Monika Goyal, M.D., M.S.C.E. Emergency Medicine and Trauma Services Moderator Adolescent Medicine II 4/24/2022 8:00 AM
Binny Chokshi, M.D., M.Ed.
Yael Smiley, M.D.		 Workshop co-leaders Applying The Collective Impact Model to Pediatric Health Interventions 4/24/2022 8:00 AM
Aisha Barber, M.D. M.Ed. Hospital Medicine Workshop co-leaders Demystifying DEI in Recruitment: Strategies for Creating a Diverse and Inclusive Residency and Fellow Training Environment 4/24/2022 8:00 AM
Panagiotis Kratimenos, M.D., Ph.D. Neonatology Oral abstract presenter Maternal Immune Activation and Hypoxia Induces Cerebellar Injury 4/24/2022 8:45 AM
Monika Goyal, M.D., M.S.C.E. Emergency Medicine and Trauma Services Co-moderator Emergency Medicine I 4/24/2022 10:00 AM
Priti Bhansali, M.D., M.Ed. Hospital Medicine Workshop co-leaders Making the Most of Peer Mentors within a Diverse Developmental Network: Supporting Scholarship and Academic Advancement 4/24/2022 10:00 AM
Ian Chua, M.D., M.H.P.E.
Gabrina Dixon, M.D., M.Ed.
Karen Smith, M.D., M.Ed.		 Hospital Medicine

 

 Workshop co-leaders The Art of Negotiation: Applying Negotiation Frameworks to Get More of What You Want in Your Academic Career 4/24/2022 10:00 AM
Matthew Magyar, M.D. Hospital Medicine Oral abstract presenter The association between social needs and unscheduled healthcare utilization among a nationally representative sample of children with asthma 4/24/2022 10:00 AM
Lena A. Saleh, M.D., M.P.H. Oral abstract presenter Machine Learning to Predict the Need for Intensive Care for Pediatric Asthma Exacerbation 4/24/2022 10:30 AM
Christina R. Rojas, M.D. Emergency Medicine and Trauma Services Oral abstract presenter Pediatric Emergency Department Undertriage for Patients with Limited English Proficiency 4/24/2022 10:30 AM
Ololade Okito, M.D. Neonatology Workshop co-leaders Best Practices in DEI Recruitment: Holistic Review and Addressing Systemic Bias 4/25/2022 8:00 AM
Jennifer H. Klein, M.D. Presenter Geography of pediatric health: Using geospatial analysis tools in pediatric care 4/25/2022 8:00 AM
Anand Gourishankar, M.B.B.S., M.R.C.P., M.A.S. Hospital Medicine Presenter Geospatial analysis in pediatric health: Principles, pitfalls, and practice 4/25/2022 8:00 AM
Sarah D. Schlatterer, M.D., Ph.D. Neurology Oral abstract presenter Autonomic Dysfunction and Hemodynamic Instability Precedes Cardiac Arrest in Infants with Congenital Heart Disease 4/25/2022 8:15 AM
Chaya Merrill, Dr.P.H. Presenter Mapping neighborhood-level inequities using the Childhood Opportunity Index 4/25/2022 8:20 AM
Jennifer H. Klein, M.D. Speaker Geospatial distribution of congenital heart disease 4/25/2022 8:40 AM
Ioannis Koutroulis, M.D., Ph.D., M.B.A. Emergency Medicine and Trauma Services Panelist APA Urgent Care SIG 4/25/2022 10:00 AM
Priti Bhansali, M.D., M.Ed. Hospital Medicine Workshop co-leaders From Mediocre to Masterly: Using Cognitive Interviewing to Improve the Validity of Your Survey 4/25/2022 10:00 AM
Beth A. Tarini, M.D., M.S. General and Community Pediatrics Speaker SPR Presidential Plenary: “Transforming the Culture of Pediatric Research: We Are the Problem and the Solution 4/25/2022 10:00 AM
Deena Berkowitz, M.D., M.P.H. Emergency Medicine and Trauma Services Speaker 2. UC fellowships and accreditation: the APA pipeline 4/25/2022 10:30 AM
John T. Kulesa, M.D. Hospital Medicine Oral abstract presenter A Descriptive Model for Prioritization and Resource Allocation in Academic Global Health Partnerships 4/25/2022 10:30 AM
Ariella Slovin, M.D. General and Community Pediatrics Speaker APA Well-being and Vitality SIG 4/25/2022 1:00 PM
Melissa Baiyewu, M.H.A., C.H.E.S.
Lin Chun-Seeley, M.A.
Desiree D. de la Torre, M.P.H., M.B.A.
Olanrewaju O. Falusi, M.D., M.Ed.
Chaya Merrill, Dr.P.H.		 General and Community Pediatrics Workshop co-leaders Training Faculty Members to Model and Teach Health Equity: A New Faculty Development Curriculum 4/25/2022 1:00 PM
Ariella Slovin, M.D. General and Community Pediatrics Speaker Wellness and Vitality SIG: Overview of endeavors to date and status report on well-being of APA Members 4/25/2022 1:30 PM
Beth A. Tarini, M.D., M.S. General and Community Pediatrics Speaker Navigating Research Careers Through the Currents of Policy and Politics 4/25/2022 1:36 PM
Rebecca S. Lundberg, M.D. Oral abstract presenter Early parenteral nutrition support and preterm cerebellar metabolic maturation 4/25/2022 2:00 PM
Aisha Barber, M.D., M.Ed. Hospital Medicine Workshop co-leader Moving with the Tide: Taking Steps Toward Anti-Racism and Equity 4/233/22 1:00 PM

 

Drs. Katie Donnelly, Panagiotis Kratimenos, Rana Hamdy, Shayna Coburn and Brynn Marks

Five Children’s National Hospital faculty named to Society for Pediatric Research

Drs. Katie Donnelly, Panagiotis Kratimenos, Rana Hamdy, Shayna Coburn and Brynn Marks

The Society for Pediatric Research (SPR) announced five new members from Children’s National Hospital: Drs. Rana Hamdy, Panagiotis Kratimenos, Brynn Marks, Shayna Coburn and Katie Donnelly.

The Society for Pediatric Research (SPR) announced five new members from Children’s National Hospital. Established in 1929, SPR’s mission is to create a multi-disciplinary network of diverse researchers to improve child health.

Membership in SPR is a recognized honor in academic pediatrics. It requires nomination by academic peers and leaders as well as recognition of one’s role as an independent, productive child health researcher.

“I am so proud of our faculty and all that they have accomplished. I am thrilled that they have been recognized for their achievements,” said Beth A. Tarini, M.D., M.S., SPR president and associate director for the Center for Translational Research at Children’s National Hospital.

SPR 2021 active new members from Children’s National are:

    • Katie Donnelly, M.D., M.P.H., attending physician in the Emergency Department at Children’s National Hospital. She is the medical director for Safe Kids DC, an organization dedicated to preventing accidental injuries in children in Washington DC. Her personal research interest is in preventing firearm injuries in children and she is a member of Safer through Advocacy, Firearm Education and Research (SAFER), a multidisciplinary team dedicated to firearm injury prevention at Children’s National. She is also the medical director of the newly founded hospital-based violence intervention program at Children’s National and an associate professor of pediatrics and emergency medicine at The George Washington University.“To be recognized by my peers as a researcher with a significant contribution to our field is very validating. It also opens a world of potential collaborations with excellent scientists, which is very exciting!” said Dr. Donnelly. “I am grateful for the immense support offered to me by the Division of Emergency Medicine to complete the research I am passionate about, especially my mentor Monika Goyal.”
    • Panagiotis Kratimenos, M.D., Ph.D., newborn intensivist and neuroscientist at Children’s National. He studies mechanisms of brain injury in the neonate, intending to prevent its sequelae later in life. Dr. Kratimenos’ interest lies in identifying therapies to prevent or improve neurodevelopmental disabilities of sick newborns caused by prematurity and perinatal insults.“Being a member of SPR is a deep honor for me. SPR has always been a ‘mentorship home’ for me since I was a trainee and a member of the SPR junior section,” said Dr. Kratimenos. “A membership in the SPR allows us to access a very diverse, outstanding team of pediatric academicians and researchers who support the development of physician-scientists, honors excellence through prestigious grants and awards, and advocates for children at any level either locally, nationally, or internationally.”
    • Rana Hamdy, M.D., M.P.H., M.S.C.E., pediatric infectious diseases physician at Children’s National and Director of the Antimicrobial Stewardship Program. She is an assistant professor of pediatrics at George Washington University School of Medicine and Health Sciences. Her area of expertise focuses on the prevention and treatment of antimicrobial resistant infections and the promotion of good antimicrobial stewardship in inpatient and outpatient settings.“It’s an honor to be joining the Society for Pediatric Research and becoming part of this distinguished multidisciplinary network of pediatric researchers,” said Dr. Hamdy. “I look forward to the opportunity to meet and work with SPR members, make connections for future collaborations, as well as encourage trainees to pursue pediatric research through the opportunities that SPR offers.”
    • Shayna Coburn, Ph.D., director of Psychosocial Services in the Celiac Disease Program at Children’s National. She is a licensed psychologist specializing in coping and interpersonal relationships in chronic illness treatment, particularly for conditions involving specialized diets. She holds an appointment as assistant professor of psychiatry and behavioral sciences at The George Washington University School of Medicine and Health Sciences. Her work has focused on promoting effective doctor-patient communication, reducing healthcare disparities and supporting successful adherence across the developmental span of childhood and adolescence. She currently has a Career Development Award from National Institute of Diabetes and Digestive and Kidney Diseases to refine and test a group intervention designed to improve self-management and quality of life in teens with celiac disease.
      “I hope that my background as a psychologist researcher will help diversify SPR. As an SPR member, I hope to encourage more opportunities for training, awards, and other programs that would be inclusive of clinician researchers who may not hold a traditional medical degree,” said Dr. Coburn.
    • Brynn Marks, M.D., M.S.-H.P.Ed., endocrinologist at Children’s National. As a clinical and translational scientist her goal is to use unique personal experiences and training to optimize both patient and provider knowledge of and behaviors surrounding diabetes technologies thereby realizing the potential of diabetes technologies improve the lives and clinical outcomes of all people living with diabetes. Her experiences as a person living with Type 1 diabetes have undoubtedly shaped her clinical and research interests in diabetes management and medical education.
      “It is an honor to be accepted for membership in the Society for Pediatric Research,” said Dr. Marks.  “Being nominated and recognized by peers in this interprofessional pediatric research community will allow me networking and growth opportunities as I continue to advance my research career.”
Neuronal network with electrical activity

Neonatal hypoxia-ischemia causes damage to the cholinergic system

Neuronal network with electrical activity

Study suggests permanent injury to the cholinergic system after neonatal hypoxia-ischemia is responsible for the poor executive functions and difficulties in learning and memory.

Newborn babies who go through periods of low oxygen — also known as hypoxic-ischemic encephalopathy — during their first hours of life often experience difficulties in learning, memory and executive functions later on. Even when treated with therapeutic hypothermia, memory deficits and executive functions remain severely affected. These functions are linked to a neurotransmitter network called the cholinergic system.

“Complications from hypoxic-ischemic brain injury contribute to one-quarter of neonatal deaths worldwide and cause significant long-term neurological morbidity,” explains Panagiotis Kratimenos, M.D., Ph.D., neonatologist at Children’s National Hospital and Assistant Professor of Pediatrics at the George Washington University School of Medicine and Health Sciences.

In a study published in the Journal of Comparative Neurology led by Frances Northington, M.D., co-director of Neurosciences Intensive Care Nursery at Johns Hopkins and Professor of Pediatrics at Johns Hopkins University School of Medicine, with contributions from Dr. Kratimenos, the authors found significant injury to the neurons of the cholinergic systems in specific parts of the brain after exposure to low oxygen and restricted blood flow. These areas included the ipsilateral medial septal nucleus (MSN), the ipsilateral nucleus basalis of Meynert (nbM) and striatum. Within the injured part of the cortex at the site of injury, acetylcholine — the neurotransmitter found in cholinergic systems — was abnormally overactivated.

The authors hypothesize that permanent injury to the cholinergic system after neonatal hypoxia-ischemia is responsible for the poor executive functions and difficulties in learning and memory.

“Because cholinergic systems can easily be manipulated pharmacologically with already established treatments that have been used in other areas of medicine, they could be a good a target for therapeutic interventions for neonates with hypoxic-ischemic encephalopathy,” says Dr. Kratimenos.

Read the full article in the Journal of Comparative Neurology.

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Children’s National Hospital at the 2021 Pediatric Academic Societies Meeting

Attending the 2021 Pediatric Academic Societies meeting this week? There will be over 20 Children’s National Hospital-affiliated participants at this year’s meeting. We have compiled their sessions into a mini schedule:

Name Program/Department Session and role Date Time
Taeun Chang, M.D.  Neonatal Neurology and Neurocritical Care Program PAS Postgraduate Course: Neonatal Neurology: HIE-focused Project-Based (Chair) Friday, 30 April

 

 9:00 AM –
4:00 PM
CT
Taeun Chang, M.D. Neonatal Neurology and Neurocritical Care Program PAS Postgraduate Course: Neonatal Neurology: HIE-focused Project-Based (Presenter) Friday, 30 April 9:30 AM – 10:00 AM
CT
Yuan-Chiao Lu, Ph.D. Developing Brain Research Laboratory Cardiology Poster: Care of the Fetus and Newborn with CHD (Presenter) Saturday, May 1 4:30 PM – 4:45 PM
CT
Chidiogo Anyigbo, M.D., M.P.H. General and Community Pediatrics Poster: Health Services Research I (Presenter)

 

 Saturday, May 1 5:15 PM – 5:30 PM
CT
Panagiotis Kratimenos, M.D. Neonatology Platform (moderator) Saturday, May 1 4:30 PM – 6:00 PM
CT
Sudeepta Basu, MBBS, MS Neonatology Hot Topic Symposia: The Neurological Implications of Abnormal Glycemia in Neonatal Encephalopathy and Prematurity (Chair) Sunday, May 2 9:00 AM – 12:00 PM
CT
Sudeepta Basu, MBBS, MS Neonatology Hot Topic Symposia: The Neurological Implications of Abnormal Glycemia in Neonatal Encephalopathy and Prematurity (Presenter) Sunday, May 2 9:55 AM – 10:15 AM
CT
Ashraf Harahsheh, M.D., F.A.C.C., F.A.A.P.

 

 Cardiology Cardiology: Heart Disease in the Older Child Sunday, May 2 10:00 AM – 12:00 PM
CT
Rana F. Hamdy, M.D., MPH, MSCE Infectious Diseases

 

 Expanding Outpatient Antibiotic Stewardship: Practical Strategies, Novel Settings, and Sociobehavioral Influences (Presenter) Sunday, May 2 10:15 AM – 10:30 AM
CT
Rana F. Hamdy, M.D., MPH, MSCE Infectious Diseases

 

 Hot Topic Debates: Antibiotic Use in Hospitalized Children (Chair) Sunday, May 2 1:00 PM – 3:00 PM
CT
John Idso, M.D. Critical Care Poster: Resuscitation and Potpourri (presenter) Sunday, May 2 2:20 PM – 2:30 PM
CT
Michael Shoykhet, M.D., Ph.D. Critical Care Medicine

 

 Critical Care Poster: Resuscitation and Potpourri (presenter) Sunday, May 2 2:20 PM – 2:30 PM
CT
Panagiotis Kratimenos, M.D. Neonatology Neonatal Neurology: Basic & Translational I (moderator) Sunday, May 2

 

 4:30 PM – 6:00 PM
CT
Monika Goyal, M.D. Emergency Medicine and Trauma Services Injury Prevention (moderator) Sunday, May 2 10:00 AM – 12:00 PM
CT
Ioannis Koutroulis, M.D., Ph.D., M.B.A. Genetic Medicine Research

 

 Emergency Medicine III (moderator) Tuesday, May 4 2:00 PM – 4:00 PM
CT
Sudeepta Basu, MBBS, MS Neonatology Neonatal Neurology: Clinical: HIE and Other Insults (moderator) Tuesday, May 4 4:30 PM – 6:00 PM
CT
Josepheen De Asis-Cruz, M.D., Ph.D. Center for the Developing Brain Neonatal Neurology: Clinical: HIE and Other Insults (presenter) Tuesday, May 4 4:30 PM – 4:45 PM
CT
Asad Bandealy, M.D., MPH
Priti Bhansali, M.D. Monika Goyal, M.D.
Sabah Iqbal, M.D. Kavita Parikh, M.D. Shilpa Patel, M.D.		 Workshop. ThisIsSTILLOurLane: Protect Kids, Not Guns Monday, May 10 9:00 AM – 11:00 AM
CT
Cara Lichtenstein, M.D. General and Community Pediatrics APA Injury Control/Advocacy Training Combined SIG (SIG Chair) Monday, May 10 1:00 PM – 3:00 PM
CT
Terry Kind, M.D., MPH General and Community Pediatrics

 

 APA Women in Medicine / Qualitative Research Combined SIG (SIG Chair) Wednesday, May 12 9:00 AM – 11:00 AM
CT

Phase I: April-30-May 4 and Phase II: May 10-June 4

PAS 2021 Virtual Schedule

Purkinje cell

Premature birth disrupts Purkinje cell function, resulting in locomotor learning deficits

Purkinje cell

Children’s National Hospital researchers explored how preterm birth disrupts Purkinje cell function, resulting in locomotor learning deficits.

As the care of preterm babies continues to improve, neonatologists face new challenges to ensure babies are protected from injury during critical development of the cerebellum during birth and immediately after birth. How does this early injury affect locomotor function, and to what extent are clinicians able to protect the brain of preterm babies?

A new peer-reviewed study by Aaron Sathyanesan, Ph.D., Panagiotis Kratimenos, M.D., Ph.D., and Vittorio Gallo, Ph.D., published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS), explores exactly what neural circuitry of the cerebellum is affected due to complications that occur around the time of birth causing these learning deficits, and finds a specific type of neurons — Purkinje cells — to play a central role.

Up until now, there has been a sparsity of techniques available to measure neuronal activity during locomotor learning tasks that engage the cerebellum. To surmount this challenge, Children’s National used a multidisciplinary approach, bringing together a team of neuroscientists with neonatologists who leveraged their joint expertise to devise a novel and unique way to measure real-time Purkinje cell activity in a pre-clinical model with clinical relevance to humans.

Researchers measured neural circuit function by pairing GCaMP6f fiber photometry, used to measure neuronal activity in the brain of a free moving subject, with an ErasmusLadder, in which it needs to travel from point A to point B on a horizontal ladder with touch-sensitive rungs that register the type and length of steps. By introducing a sudden obstacle to movement, researchers observed how the subject coped and learned accordingly to avoid this obstacle. By playing a high-pitch tone just before the obstacle was introduced, researchers were able to measure how quickly the subjects were able to anticipate the obstacle and adjust their steps accordingly. Subjects with neonatal brain injury and normal models were run through a series of learning trials while simultaneously monitoring brain activity. In this way, the team was able to quantify cerebellum-dependent locomotor learning and adaptive behavior, unlocking a functional and mechanistic understanding of behavioral pathology that was previously unseen in this field.

In addition to showing that normal Purkinje cells are highly active during movement on the ErasmusLadder, the team explored the question of whether Purkinje cells of injured pre-clinical models were generally non-responsive to any kind of stimuli. They found that while Purkinje cells in injured subjects responded to puffs of air, which generally cue the subject to start moving on the ErasmusLadder, dysfunction in these cells was specific to the period of adaptive learning. Lastly, through chemogenetic inhibition, which specifically silences neonatal Purkinje cell activity, the team was able to mimic the effects of perinatal cerebellar injury, further solidifying the role of these cells in learning deficits.

The study results have implications for clinical practice. As the care of premature babies continues to improve, neonatologists face new challenges to ensure that babies not only survive but thrive. They need to find ways to prevent against the lifelong impacts that preterm birth would otherwise have on the cerebellum and developing brain.

Read the full press release here.

Read the full journal article here.

structure of EGFR

Study suggests EGFR inhibition reverses alterations induced by hypoxia

structure of EGFR

The study suggests that specific molecular responses modulated by EGFR (seen here) may be targeted as a therapeutic strategy for HX injury in the neonatal brain.

Hypoxic (HX) encephalopathy is a major cause of death and neurodevelopmental disability in newborns. While it is known that decreased oxygen and energy failure in the brain lead to neuronal cell death, the cellular and molecular mechanisms of HX-induced neuronal and glial cell damage are still largely undefined.

Panagiotis Kratimenos, M.D., and colleagues from the Center for Neuroscience Research at the Children’s National Research Institute, discovered increased expression of activated-epidermal growth factor receptor (EGFR) in affected cortical areas of neonates with HX and decided to further investigate the functional role of EGFR-related signaling pathways in the cellular and molecular changes induced by HX in the cerebral cortex.

The researchers found that HX-induced activation of EGFR and Ca2+/calmodulin kinase IV (CaMKIV) caused cell death and pathological alterations in neurons and glia. EGFR blockade inhibited CaMKIV activation, attenuated neuronal loss, increased oligodendrocyte proliferation and reversed HX-induced astrogliosis.

The researchers also performed, for the first time, high-throughput transcriptomic analysis of the cortex to define molecular responses to HX and to uncover genes specifically involved in EGFR signaling in brain injury. Their results indicate that specific molecular responses modulated by EGFR may be targeted as a therapeutic strategy for HX injury in the neonatal brain.

This study defines many new exciting avenues of scientific exploration to further elucidate the beneficial impact of EGFR blockade on perinatal brain injury at the cellular and molecular levels. This analysis could potentially result in the identification of new therapeutic targets associated with EGFR signaling in the developing mammalian brain that are linked with specific long-term abnormalities caused by perinatal brain injury.

Children’s National researchers who contributed to this study include Panagiotis Kratimenos, M.D., Ioannis Koutroulis, M.D., Ph.D., M.B.A., Susan Knoblach, Ph.D., Payal Banerjee, Surajit Bhattacharya, Ph.D., Maria Almira-Suarez, M.D., and Vittorio Gallo, Ph.D.

Read the full article in iScience.

allopregnanolone molecule

Autism spectrum disorder risk linked to insufficient placental steroid

allopregnanolone molecule

A study led by Children’s National Hospital and presented during Neuroscience 2019 finds that loss of allopregnanolone, a key hormone supplied by the placenta, leads to long-term structural alterations of the cerebellum – a brain region essential for smooth motor coordination, balance and social cognition – and increases the risk of developing autism.

An experimental model study suggests that allopregnanolone, one of many hormones produced by the placenta during pregnancy, is so essential to normal fetal brain development that when provision of that hormone decreases – as occurs with premature birth – offspring are more likely to develop autism-like behaviors, a Children’s National Hospital research team reports at the Neuroscience 2019 annual meeting.

“To our knowledge, no other research team has studied how placental allopregnanolone (ALLO) contributes to brain development and long-term behaviors,” says Claire-Marie Vacher, Ph.D., lead author. “Our study finds that targeted loss of ALLO in the womb leads to long-term structural alterations of the cerebellum – a brain region that is essential for motor coordination, balance and social cognition ­– and increases the risk of developing autism,” Vacher says.

According to the Centers for Disease Control and Prevention, about 1 in 10 infants is born preterm, before 37 weeks gestation; and 1 in 59 children has autism spectrum disorder.

In addition to presenting the abstract, on Monday, Oct. 21, Anna Penn, M.D., Ph.D., the abstract’s senior author, will discuss the research with reporters during a Neuroscience 2019 news conference. This Children’s National abstract is among 14,000 abstracts submitted for the meeting, the world’s largest source of emerging news about brain science and health.

ALLO production by the placenta rises in the second trimester of pregnancy, and levels of the neurosteroid peak as fetuses approach full term.

To investigate what happens when ALLO supplies are disrupted, a research team led by Children’s National created a novel transgenic preclinical model in which they deleted a gene essential in ALLO synthesis. When production of ALLO in the placentas of these experimental models declines, offspring had permanent neurodevelopmental changes in a sex- and region-specific manner.

“From a structural perspective, the most pronounced cerebellar abnormalities appeared in the cerebellum’s white matter,” Vacher adds. “We found increased thickness of the myelin, a lipid-rich insulating layer that protects nerve fibers. From a behavioral perspective, male offspring whose ALLO supply was abruptly reduced exhibited increased repetitive behavior and sociability deficits – two hallmarks in humans of autism spectrum disorder.”

On a positive note, providing a single ALLO injection during pregnancy was enough to avert both the cerebellar abnormalities and the aberrant social behaviors.

The research team is now launching a new area of research focus they call “neuroplacentology” to better understand the role of placenta function on fetal and newborn brain development.

“Our team’s data provide exciting new evidence that underscores the importance of placental hormones on shaping and programming the developing fetal brain,” Vacher notes.

  • Neuroscience 2019 presentation
    Sunday, Oct. 20, 9:30 a.m. (CDT)
    “Preterm ASD risk linked to cerebellar white matter changes”
    Claire-Marie Vacher, lead author; Sonia Sebaoui, co-author; Helene Lacaille, co-author; Jackie Salzbank, co-author; Jiaqi O’Reilly, co-author; Diana Bakalar, co-author; Panagiotis Kratimenos, M.D., neonatologist and co-author; and Anna Penn, M.D., clinical neonatologist and developmental neuroscientist and senior author.
newborn in incubator

Working to reduce brain injury in newborns

A new study from Children’s National Health System and Drexel University College of Medicine has identified a promising treatment to reduce or prevent brain injury in newborns who have suffered hypoxia-ischemia.

Research-clinicians at Children’s National Health System and Drexel University College of Medicine led the first study to identify a promising treatment to reduce or prevent brain injury in newborns who have suffered hypoxia-ischemia, a serious complication in which restricted blood flow deprives the brain of oxygen.

Consequences of brain injury resulting from oxygen deprivation affect the entire lifespan and range from mild (learning disabilities) to severe (inability to breathe, walk, talk or see). This complication can occur during or before birth due to maternal/placental problems, such as placental abruption or cord prolapse, or due to fetal/newborn issues, such as asphyxia due to labor difficulties, infection, fetal-maternal bleeding or twin-to-twin transfusion.

Published in Neonatology on Oct. 13, 2017, the study evaluated newborn experimental models exposed to hypoxia-ischemia. The experimental models were given standard cooling therapy (therapeutic hypothermia) alone and in combination with a selective Src kinase inhibitor, PP2, that blocks a regulatory enzyme of apoptosis (cell death), which intensifies as a result of hypoxia-ischemia. The Food and Drug Administration has approved a Src kinase inhibitor as an oncology treatment. This study is the first to test the benefits of blocking this enzyme in reducing the neurological damage caused by brain hypoxia-ischemia.

“In hypoxia-ischemia, CaM kinase is over-activated, but hypothermia has been shown to decrease this enzyme’s activation. We theorized that a Src kinase inhibitor, in addition to hypothermia, would further attenuate the activation of CaM kinase IV and that the result might be less brain damage,” explains Panagiotis Kratimenos, M.D., Ph.D., the study’s lead author, and a specialist in neonatology and neonatal neurocritical care at Children’s National. “From this study, we were pleased that this seems to be the case.”

The research team assessed neuropathology, adenosine triphosphate and phosphocreatine  concentrations as well as CaM kinase IV activity. The CaM kinase IV activity in cerebral tissue was 2,002 (plus or minus 729) with normal oxygen levels and in normal temperatures, 4,104 (plus or minus 542) in hypoxia with hypothermia treatment, and 2,165 (plus or minus 415) in hypoxia with hypothermia treatment combined with PP2 administration.

The authors conclude that hypothermia alone attenuated the over-activation of CaM kinase IV and improved neuropathology after hypoxia. However, the combination of hypothermia with Src kinase inhibition following hypoxia further attenuated the increased activation of CaM kinase IV, compared with hypothermia alone in the newborn experimental model brain.

Currently, the only treatment for hypoxia-ischemia is therapeutic hypothermia. Starting in the first six hours of life, doctors in the neonatal intensive care unit lower a baby’s temperature by about 3 degrees Celsius for three days. This therapy is proven to reduce neural defects by up to 30 percent, yet many infants still have poor outcomes even after the therapeutic cooling treatment.

“In oxygen deprivation of the brain, the pathways leading to cell death are over-activated, including the nuclear enzyme CaM kinase IV. We sought to intervene in this pathway to reduce the heightened cell death, which leads to brain damage,” explains Dr. Kratimenos, an assistant professor of pediatrics at The George Washington University School of Medicine and Health Sciences whose research focus is neonatal encephalopathy and therapeutic hypothermia.

To continue preclinical research into this approach, Dr. Kratimenos envisions studying the effect of other types of small molecule inhibitors to target the apoptotic cascade, perhaps in multiple doses, eliminating the potential side effects, and determining the best dose and duration of treatment.

“If confirmed by further studies, this approach─in combination with cooling─may help to further attenuate neurological damage that babies suffer after experiencing hypoxia-ischemia,” says Dr. Kratimenos.

The study co-authors include Ioannis Koutroulis, M.D., Ph.D., a faculty member in Children’s Division of Emergency Medicine; and Amit Jain, M.D.; Shadi Malaeb, M.D.; and the world-renowned neonatologist and pioneer in bioenergetics of the brain, Maria Delivoria-Papadopoulos, M.D., all of the Drexel University College of Medicine.