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Biochemical, cellular, and molecular mechanisms in the evolution of secondary damage after severe traumatic brain injury in infants and children: Lessons learned from the bedside

Kochanek, Patrick M. MD, FCCM; Clark, Robert S.B. MD; Ruppel, Randall A. MD; Adelson, P. David MD; Bell, Michael J. MD; Whalen, Michael J. MD; Robertson, Courtney L. MD; Satchell, Margaret A. MD; Seidberg, Neal A. MD; Marion, Donald W. MD; Jenkins, Larry W. PhD

Pediatric Critical Care Medicine: July 2000 - Volume 1 - Issue 1 - p 4-19
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Objective To present a state-of-the-art review of mechanisms of secondary injury in the evolution of damage after severe traumatic brain injury in infants and children.

Data Sources We reviewed 152 peer-reviewed publications, 15 abstracts and proceedings, and other material relevant to the study of biochemical, cellular, and molecular mechanisms of damage in traumatic brain injury. Clinical studies of severe traumatic brain injury in infants and children were the focus, but reports in experimental models in immature animals were also considered. Results from both clinical studies in adults and models of traumatic brain injury in adult animals were presented for comparison.

Data Synthesis Categories of mechanisms defined were those associated with ischemia, excitotoxicity, energy failure, and resultant cell death cascades; secondary cerebral swelling; axonal injury; and inflammation and regeneration.

Conclusions A constellation of mediators of secondary damage, endogenous neuroprotection, repair, and regeneration are set into motion in the brain after severe traumatic injury. The quantitative contribution of each mediator to outcome, the interplay between these mediators, and the integration of these mechanistic findings with novel imaging methods, bedside physiology, outcome assessment, and therapeutic intervention remain an important target for future research.

From the Safar Center for Resuscitation Research (Drs. Kochanek, Clark, Ruppel, Adelson, Robertson, Satchell, Seidberg, Marion, and Jenkins), the Departments of Anesthesiology and Critical Care Medicine (Drs. Kochanek, Clark, Ruppel, Robertson, Satchell, and Seidberg), Pediatrics (Drs. Kochanek and Clark), Neurological Surgery (Drs. Adelson, Marion, and Jenkins), the Center for Injury Control and Research (Drs. Marion and Kochanek,), and the Brain Trauma Research Center (Drs. Marion, Kochanek, Clark, Adelson, and Jenkins), of the University of Pittsburgh School of Medicine and Children’s Hospital of Pittsburgh, Pittsburgh, PA; the Children’s Hospital National Medical Center (Dr. Bell), Washington, D.C.; and Massachusetts General Hospital (Dr. Whalen), Boston, MA.

Address requests for reprints to: Patrick M. Kochanek, MD, Safar Center for Resuscitation Research, 3434 Fifth Ave., Pittsburgh, PA 15260. E-mail: kochanekpm@anes.upmc.edu

Supported, in part, by National Institutes of Health grants NINDS NS38087 (PMK), NS38620 (RSBC), NS01809 (PDA), and NS30318 (DWM, PMK), the Laerdal Foundation, the Charles Schertz Fellowship Grant from the Department of Anesthesiology and Critical Care Medicine, University of Pittsburgh School of Medicine (MJW, RR), and by the GCRC of Children’s Hospital of Pittsburgh (PDA, PMK) for investigation of the individual mechanisms studied in this work.

© 2000 Lippincott Williams & Wilkins, Inc.