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 (Pbto(2)) 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 Pbto(2) compared with sham. Pbto(2) 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, Pbto(2) 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 Pbto(2) 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.
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 (Pbto(2)) 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 Pbto(2) compared with sham. Pbto(2) 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, Pbto(2) 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 Pbto(2) 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.
Authors: P Vajkoczy; H Roth; P Horn; T Lucke; C Thomé; U Hubner; G T Martin; C Zappletal; E Klar; L Schilling; P Schmiedek Journal: J Neurosurg Date: 2000-08 Impact factor: 5.115
Authors: P David Adelson; Susan L Bratton; Nancy A Carney; Randall M Chesnut; Hugo E M du Coudray; Brahm Goldstein; Patrick M Kochanek; Helen C Miller; Michael P Partington; Nathan R Selden; Craig R Warden; David W Wright Journal: Pediatr Crit Care Med Date: 2003-07 Impact factor: 3.624
Authors: Stuart H Friess; Colin Smith; Todd J Kilbaugh; Suzanne G Frangos; Jill Ralston; Mark A Helfaer; Susan S Margulies Journal: Crit Care Med Date: 2012-08 Impact factor: 7.598
Authors: D Kacy Cullen; James P Harris; Kevin D Browne; John A Wolf; John E Duda; David F Meaney; Susan S Margulies; Douglas H Smith Journal: Methods Mol Biol Date: 2016
Authors: Stuart H Friess; Benjamin Bruins; Todd J Kilbaugh; Colin Smith; Susan S Margulies Journal: J Neurotrauma Date: 2014-11-24 Impact factor: 5.269