Citation

Friess SH, Ralston J, Eucker SA, Helfaer MA, Smith C, Margulies SS. Neurosurgery 2011; 69(5): 1139-1147.

Affiliation

*Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania ‡Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania §Department of Neuropathology, Western General Hospital, Edinburgh, Scotland, United Kingdom.

Copyright

(Copyright © 2011, Congress of Neurological Surgeons)

DOI

10.1227/NEU.0b013e3182284aa1

PMID

21670716

PMCID

PMC3188667

Abstract

BACKGROUND: Small-animal models have been used in traumatic brain injury (TBI) research to investigate the basic mechanisms and pathology of TBI. Unfortunately, successful TBI investigations in small-animal models have not resulted in marked improvements in clinical outcomes of TBI patients. OBJECTIVE: To develop a clinically relevant immature large-animal model of pediatric neurocritical care following TBI. METHODS: Eleven 4-week-old piglets were randomly assigned to either rapid axial head rotation without impact (n = 6) or instrumented sham (n = 5). All animals had an intracranial pressure monitor, brain tissue oxygen tension (Pbto2) probe, and cerebral microdialysis probe placed in the frontal lobe and data collected for 6 hours following injury. RESULTS: Injured animals had sustained elevations in intracranial pressure and lactate-pyruvate ratio (LPR), and decreased Pbto2 compared with sham. Pbto2 and LPR from separate frontal lobes had strong linear correlation in both sham and injured animals. Neuropathologic examination demonstrated significant axonal injury and infarct volumes in injured animals compared with sham at 6 hours postinjury. Averaged over time, Pbto2 in both injured and sham animals had a strong inverse correlation with total injury volume. Average LPR had a strong correlation with total injury volume. CONCLUSION: LPR and Pbto2 can be utilized as serial nonterminal secondary markers in our injury model for neuropathology, and as evaluation metrics for novel interventions and therapeutics in the acute postinjury period. This translational model bridges a vital gap in knowledge between TBI studies in small-animal models and clinical trials in the pediatric TBI population. ABBREVIATIONS: ANOVA: analysis of varianceβ-APP: β-amyloid precursor proteinCPP: cerebral perfusion pressureH&E: hematoxylin and eosinICP: intracranial pressureLPR: lactate-pyruvate ratioPbto2: brain tissue oxygen tensionTBI: traumatic brain injury.

Language: en