Massachusetts General Hospital

Members of the Brain Trauma Lab

Overview

Our research is focused on understanding the immature brain and its response to injury and other conditions early in life, with the goal of helping infants and children. Traumatic brain injury is the single most common cause of death and disability in children in the United States, and in many other countries as well. An infant’s brain is different from that of a grade-school child, which is different from that of an adolescent, and we are working to understand these differences and how they influence both response to injury and to repair and recovery.  Children who are injured may have lifetime problems which we don’t know yet how to prevent or help. Our work is aimed at learning how to better treat the millions of children with this and similar problems, now and in the future.

Current Projects focus on:

• Studying the neuropathogenesis of traumatic brain injury
• Using MRI to non-invasively screen and evaluate brain injury
• Characterization of biomarkers after brain injury
• Using instrumented helmets to study what mechanisms are linked to specific brain problems in young athletes
• Studying the mechanisms of brain injury after non-accidental trauma in infants and children
• The effect of age and gender on lesion development after injury
• The ability of the brain to make new neurons after brain injury
• Evaluating cyclosporin A as a therapeutic after brain injury
• The effect of anesthetics on the developing brain

Group Members

• Ann-Christine (Tina) Duhaime, MD, Program Director
• Beth A. Costine, PhD, Co-investigator
• Carter Dodge, MD, Co-investigator
• Jennifer Munoz, MD, Fellow
• Numa Perez, Harvard Medical Student
• Kristen Saliga, BS, Lab Manager
• Sabrina Taylor, BS, PhD Candidate

Research Projects

• Common Data Elements: Clinical researchers in pediatric neurosurgery at MassGeneral Hospital for Children are participating in national studies designed to gather sophisticated data on traumatic brain injury from large numbers of adults and children. Information gleaned from these studies will ultimately be integrated into stratified, multidisciplinary treatment trials for infants, children and adults with various types of traumatic brain injuries, as well as investigating host factors, such as genetics, which influence outcome 

• Evaluation of Cyclosporin A as a therapeutic after traumatic brain injury. Cyclosporin A blocks the opening of the mitochondrial transition pore. After brain insults, when the cell senses that conditions are poor, the pore opens elminating the proton gradient and initiating apoptosis. Cyclosporin A may prevent injury on a cellular level after traumatic brain injury. The project is in collaboration with researchers at the University of Pennsylvania

• The postnatal brain makes new neurons in a process called neurogenesis. We are studying the areas of the brain where neurogenesis occurs: the subventricular zone and the dentate gyrus of the hippocampus and are determining if neurogenesis increases after traumatic brain injury and if these new neurons aid in the repair process or perhaps, do not migrate properly and become foci for seizure development.  This project is in collaboration with pediatric neuropathologists located at the University of Edinburgh and Georgetown University

• We are evaluating peripheral proteins in the serum that may serve as serum markers for traumatic brain injury indicating the degree of injury and predicting outcome. Serum markers in the pediatric population present a particular challenge as body composition differs from adults

• Unfortunately, not all traumatic brain injury is accidental in infants and toddlers, but inflicted. These children develop similar injuries that often results in a subdural hematoma, apnea and development of seizures. When evaluated via magnetic resonance imaging, the hemisphere underlying the hematoma will often regress resulting in a large black area where the brain has regressed: “big black brain”. We are using advanced magnetic resonance imaging to determine the early mechanisms of the processes of the injured hemisphere and hope to develop treatments to combat this devastating condition. This project is in collaboration with scientists at the Martinos Institute at Massachusetts General Hospital, with a pediatric neuroradiolgist at Texas Children’s Hospital, and a pediatric anesthesiologist at The Children’s Hospital at Dartmouth

• In collaboration with Symbex and scientists at Dartmouth College, we are using helmets fitted with accelerometers to characterize the number contacts and the forces that football players experience during football practice and games at the high school and college level. We are also in the process of using these accelerometer-fitted helmets in toddlers to characterize the actual forces involved in real falls

• We are developing rapid sequences of MRI to screen for head injury to replace screening with CT scans in order to reduce exposure of children to radiation

• All neurosurgeries and many clinical procedures in children require anesthesia. The immature brain is unique in that γ-aminobutyric acid (GABA) is the major neurotransmitter and is required for normal synaptic development and dendrite outgrowth making the immature brain potentially susceptible to anesthetic agents that target the GABA receptor

Research Positions

Research internships for undergraduates and medical students are sometimes available in this lab.  As a Harvard-affiliated institution, in general, preference is given to Harvard students, although others also are considered. 

For information please contact Dr. Costine at bcostine@partners.org.

Concussion

When neurosurgeon Tina Duhaime, MD, of the MGH Youth Sports Concussion Clinic, talks with families about concussion, she takes time to explain what is known, and just as importantly, what isn’t known, about this common injury.

Publications

Dr. Duhaime:

Crisco JJ, Wilcox BJ, Machan JT, McAllister TW, Duhaime AC, Duma SM, Rowson S, Beckwith JG, Chu JJ, Greenwald RM. Magnitude of Head Impact Exposures in Individual Collegiate Football Players. J Appl Biomech. 2011 Aug 26. [Epub ahead of print] View in: PubMed

Crisco JJ, Wilcox BJ, Beckwith JG, Chu JJ, Duhaime AC, Rowson S, Duma SM, Maerlender AC, McAllister TW, Greenwald RM. Head impact exposure in collegiate football players. J Biomech. 2011 Oct 13;44(15):2673-8. Epub 2011 Aug 27. View in:PubMed

Brainard LL, Beckwith JG, Chu JJ, Crisco JJ, McAllister TW, Duhaime AC, Maerlender AC, Greenwald RM. Gender Differences in Head Impacts Sustained by Collegiate Ice Hockey Players. Med Sci Sports Exerc. 2011 Jun 28. [Epub ahead of print] View in: PubMed

Duhaime AC, Holshouser B, Hunter JV, Tong K. Common Data Elements for Neuroimaging of Traumatic Brain Injury: Pediatric Considerations. J Neurotrauma. 2011 Jun 14. [Epub ahead of print] View in: PubMed

Duhaime AC, Schwartz D. Monitoring in young patients. J Neurosurg Pediatr. 2011 Apr;7(4):329; discussion 330. View in: PubMed

Duhaime AC.Traumatic brain injuries. J Neurosurg. 2011 Feb;114(2):543; discussion 544. Epub 2010 Nov 19. View in:PubMed

Crisco JJ, Fiore R, Beckwith JG, Chu JJ, Brolinson PG, Duma S, McAllister TW, Duhaime AC, Greenwald RM. Frequency and location of head impact exposures in individual collegiate football players. J Athl Train. 2010 Nov-Dec;45(6):549-59. View in:PubMed

Duhaime AC, Gean AD, Haacke EM, Hicks R, Wintermark M, Mukherjee P, Brody D, Latour L, Riedy G. Common data elements in radiologic imaging of traumatic brain injury.; Common Data Elements Neuroimaging Working Group Members, Pediatric Working Group Members. Arch Phys Med Rehabil. 2010 Nov;91(11):1661-6. Review. View in:PubMed

Timmons SD, Duhaime AC, Lee SM. Mild traumatic brain injury. Introduction. Neurosurg Focus. 2010 Nov;29(5):1. View in: PubMed

Haacke EM, Duhaime AC, Gean AD, Riedy G, Wintermark M, Mukherjee P, Brody DL, DeGraba T, Duncan TD, Elovic E, Hurley R, Latour L, Smirniotopoulos JG, Smith DH. Common data elements in radiologic imaging of traumatic brain injury. J Magn Reson Imaging. 2010 Sep;32(3):516-43. Review. View in:PubMed

Duhaime AC. Imitation, immaturity, and injury. J Neurosurg Pediatr. 2009 Nov;4(5):407; discussion 407. View in:PubMed

Missios S, Harris BT, Dodge CP, Simoni MK, Costine BA, Lee YL, Quebada PB, Hillier SC, Adams LB, Duhaime AC. Scaled cortical impact in immature swine: effect of age and gender on lesion volume. J Neurotrauma. 2009 Nov;26(11):1943-51.View in:PubMed

Chiesa A, Duhaime AC.Abusive head trauma. Pediatr Clin North Am. 2009 Apr;56(2):317-31. Review. View in: PubMed

Missios S, Quebada PB, Forero JA, Durham SR, Pekala JS, Eskey CJ, Duhaime AC. Quick-brain MRI for non-hydrocephalus indications. 2009. J Neurosurg Pediatrics 2(6):438-444, 2008. View in: PubMed

Saatman KE, Duhaime AC, Manley GT, and Workshop Scientific Team and Advisory Panel Members. Classification of traumatic brain injury for targeted therapies. J Neurotrauma 25:719-738, 2008. View in: PubMed

Koob AO, Harris B, Duhaime AC. Cellular genesis in the postnatal piglet. International Journal of Developmental Neuroscience 26(6):641-646, 2008; Epub 2008 Apr 16, 2008. View in: PubMed

Duhaime AC, Dodge CP. Closer but not there yet: models in child injury research. J Neurosurg Pediatr. 2008 Nov;2(5):320; author reply 320. View in:PubMed

Durham SR, Duhaime AC. Basic science: Maturation-dependent response of the immature brain to experimental subdural hematoma. Journal of Neurotrauma 24(1):5-14, 2007. View in: PubMed

Duhaime AC, Durham SR. Traumatic brain injury in infants: the phenomenon of subdural hemorrhage with hemispheric hypodensity (“Big Black Brain”). Progress in Brain Research, Volume 161, pages 287-296, 2007. View in: PubMed

Judkins AR, Porter B, Cook N, Clancy RR, Duhaime AC, Golden JA. Dystrophic neuritic processes in epileptic cortex. Epilepsy Research 70(1):49-58, 2006. View in: PubMed

Duhaime AC, Saykin AJ, McDonald BC, Dodge CP, Eskey CJ, Darcey TM, Grate LL, Tomashosky P. Functional magnetic resonance imaging of the primary somatosensory cortex in piglets. J Neurosurgery (4 Suppl Pediatrics) 104:259-264, April 2006 . View in: PubMed

Duhaime AC. Large animal models of traumatic injury to the immature brain. Developmental Neuroscience 28:380-387, 2006. View in: PubMed

Grate LL, Golden JA, Hoopes PJ, Hunter JV, Duhaime AC. Traumatic brain injury in piglets of different ages: techniques for lesion analysis using histology and magnetic resonance imaging. Journal of Neuroscience Methods 123(2):201-206, 2003. View in: PubMed

Simon SL, Telfeian A, Duhaime AC . Complications of invasive monitoring used in intractable pediatric epilepsy. Pediatric Neurosurgery 38(1):47-52, 2003. View in: PubMed

Prange MT, Coats B, Duhaime AC, Margulies SS. Anthropomorphic simulations of falls, shakes, and inflicted impacts in infants. J Neurosurgery 99(1):143-150, 2003. View in: PubMed

Duhaime AC, Hunter JV, Grate LL, Kim A, Golden J, Demidenko E, Harris B. Magnetic resonance imaging studies of age-dependent responses to scaled focal brain injury in the piglet. J Neurosurgery 99(3):542-548, 2003. View in: PubMed

Porter BE, Judkins AR, Clancy RR, Duhaime A, Dlugos DJ, Golden JA. Dysplasia: a common finding in intractable pediatric temporal lobe epilepsy. Neurology 61(3):365-8, 2003. View in: PubMed

Duhaime AC, Partington MD. Overview and Clinical Presentation of Inflicted Head Injury in Infants. In: Non-accidental Head Injuries in Infants, Neurosurgery Clinics of North America 13(2):149-154, 2002. View in: PubMed

Schutzman SA, Barnes P, Duhaime AC, Greenes D, Homer C, Jaffe D, Lewis RJ, Luerssen TG, Schunk J. Evaluation and management of children younger than two years with apparently minor head trauma: Proposed guidelines. Pediatrics 107(5):983-993, 2001. View in: PubMed

Crino PB, Duhaime AC, Baltuch G, White R. Differential expression of glutamate and GABA A receptor mRNA in cortical dysplasia. Neurology 56(7):906-13, 2001. View in: PubMed

Durham S, Clancy RR, Leuthardt E, Sun P, Kamerling S, Dominguez T, Duhaime AC. CHOP Infant Coma Scale (“Infant Face Scale”): A novel coma scale for children less than two years of age. J Neurotrauma 17(9):729-737, 2000. View in: PubMed

Duhaime AC, Margulies SS, Durham SR, O’Rourke MM, Golden JA, Marwaha S, Raghupathi R. Maturation-dependent response of the piglet brain to scaled cortical impact. J Neurosurgery 93:455-462, 2000. View in: PubMed

Durham SR, Raghupathi R, Helfaer MA, Marwaha S, Duhaime AC. Age-related differences in acute physiologic response to focal traumatic brain injury in piglets. Pediatric Neurosurgery 33(2):76-82, 2000. View in: PubMed

Beth Costine, PhD:

Costine BA, Oberlander JG, Davis MC, Penatti CA, Porter DM, Leaton RN, Henderson LP. Chronic anabolic androgenic steroid exposure alters corticotropin releasing factor expression and anxiety-like behaviors in the female mouse. Psychoneuroendocrinology. 2010 Nov; 35(10):1473-85. View in: PubMed

Missios S, Harris BT, Dodge CP, Simoni MK, Costine BA, Lee YL, Quebada PB, Hillier SC, Adams LB, Duhaime AC. Scaled cortical impact in immature swine: effect of age and gender on lesion volume. J Neurotrauma. 2009 Nov; 26(11):1943-51. View in: PubMed

Penatti CA, Costine BA, Porter DM, Henderson LP. Effects of chronic exposure to an anabolic androgenic steroid cocktail on alpha5-receptor-mediated GABAergic transmission and neural signaling in the forebrain of female mice. Neuroscience. 2009 Jun 30; 161(2):526-37. View in: PubMed

Clark AS, Costine BA, Jones BL, Kelton-Rehkopf MC, Meerts SH, Nutbrown-Greene LL, Penatti CA, Porter DM, Yang P, Henderson LP. Sex- and age-specific effects of anabolic androgenic steroids on reproductive behaviors and on GABAergic transmission in neuroendocrine control regions. Brain Res. 2006 Dec 18; 1126(1):122-38. View in: PubMed

Costine BA, Inskeep EK, Blemings KP, Flores JA, Wilson ME. Mechanisms of reduced luteal sensitivity to prostaglandin F2alpha during maternal recognition of pregnancy in ewes. Domest Anim Endocrinol. 2007 Feb; 32(2):106-21. View in: PubMed

Costine BA, Inskeep EK, Wilson ME. Growth hormone at breeding modifies conceptus development and postnatal growth in sheep. J Anim Sci. 2005 Apr; 83(4):810-5. View in: PubMed

Choudhary E, Costine BA, Wilson ME, Inskeep EK, Flores JA. Prostaglandin F2alpha (PGF2alpha) independent and dependent regulation of the bovine luteal endothelin system. Domest Anim Endocrinol. 2004 Jul; 27(1):63-79. View in: PubMed

Costine BA, Sayre BL, Inskeep EK. Embryotoxicity of regressing corpora lutea in ewes. Reproduction. 2001 Dec; 122(6):883-7. View in: PubMed

Wulster-Radcliffe MC, Costine BA, Lewis GS. Estradiol-17 beta-oxytocin-induced cervical dilation in sheep: application to transcervical embryo transfer. J Anim Sci. 1999 Oct; 77(10):2587-93. View in: PubMed

Dr. Ann-Christine (Tina) Duhaime

Phone: 617-643-9175
Fax: 617-726-7546

Public Transportation Access: yes

Dr. Beth Costine
Building 149, Room 3.340
13^th Street
Charlestown, MA 02129
Phone: 617-643-9271
Fax: 617-643-9446