New in vitro model of traumatic neuronal injury: evaluation of secondary injury and glutamate receptor-mediated neurotoxicity.
The multiplicity and complexity of secondary injury processes following brain trauma in vivo make it difficult to elucidate the roles of specific injury mechanisms. As with other areas of CNS injury, such as ischemia, this has led to the development of in vitro models. Here we describe a new trauma model, in which standardized trauma is delivered to neuronal/glial cultures using a special mechanical device that produces concentric circular cuts in the cell layer. Changes in the number of circles (from 1 to 6) allows variation of injury severity. Comparison studies of cell death induced by such trauma in glial and neuronal/glial cultures demonstrated that glial cells are relatively resistant to this injury, and that the cell death after trauma to neuronal/glial cultures reflects primarily neuronal death. Consistent with other in vivo and in vitro studies, glutamate receptor antagonists MK 801 and MCPG were neuroprotective. Thus, this model appears useful for studying glutamatergic mechanisms involved in secondary injury, and may prove useful for evaluating certain pharmacological strategies for CNS trauma.
Mukhin
A G
AG
Georgetown Institute for Cognitive and Computational Sciences and Department of Neurology, Georgetown University Medical Center, Washington, D.C. 20007-2197, USA.
Ivanova
S A
SA
Knoblach
S M
SM
Faden
A I
AI
D000818:Animals; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology*; D016022:Case-Control Studies; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000293:injuries* / Q000503:physiopathology; D018920:Coculture Techniques; D003430:Cross-Sectional Studies; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D016014:Linear Models; D008137:Longitudinal Studies; D009410:Nerve Degeneration / Q000503:physiopathology; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000502:physiology*; D015599:Trauma Severity Indices
D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D017470:Receptors, Glutamate; D007770:L-Lactate Dehydrogenase