title: In vitro models of traumatic brain injury.
abstract: In vitro models of traumatic brain injury (TBI) are helping elucidate the pathobiological mechanisms responsible for dysfunction and delayed cell death after mechanical stimulation of the brain. Researchers have identified compounds that have the potential to break the chain of molecular events set in motion by traumatic injury. Ultimately, the utility of in vitro models in identifying novel therapeutics will be determined by how closely the in vitro cascades recapitulate the sequence of cellular events that play out in vivo after TBI. Herein, the major in vitro models are reviewed, and a discussion of the physical injury mechanisms and culture preparations is employed. A comparison between the efficacy of compounds tested in vitro and in vivo is presented as a critical evaluation of the fidelity of in vitro models to the complex pathobiology that is TBI. We conclude that in vitro models were greater than 88% predictive of in vivo results.
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA. bm2119@columbia.edu
authors.forename: Barclay
authors.initials: B
authors.lastname: Morrison
authors.forename: Benjamin S
authors.initials: BS
authors.lastname: Elkin
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Dollé
authors.forename: Martin L
authors.initials: ML
authors.lastname: Yarmush
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000503:physiopathology; D001930:Brain Injuries / Q000503:physiopathology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D018929:Cell Culture Techniques / Q000379:methods*; D002461:Cell Line, Transformed; D004195:Disease Models, Animal; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D008954:Models, Biological; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D058914:Purinergic Antagonists / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors; D058468:Receptors, Ionotropic Glutamate / Q000037:antagonists & inhibitors; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors; D011983:Receptors, Purinergic / Q000187:drug effects; D015203:Reproducibility of Results; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D058914:Purinergic Antagonists; D017382:Reactive Oxygen Species; D058468:Receptors, Ionotropic Glutamate; D018094:Receptors, Metabotropic Glutamate; D011983:Receptors, Purinergic; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D019001:Nitric Oxide Synthase; D020928:Mitogen-Activated Protein Kinases