Differences in cell death between high and low energy brain injury in adult rats.
BACKGROUND
Traumatic brain damage is dependent on energy transfer to the brain at impact. Different injury mechanisms may cause different types of brain injury. It is, however, unknown if the relative distribution between apoptotic cell-death and necrotic cell- death in different populations of brain cells varies depending on energy transfer.


METHODS
Experimental contusions were produced with a modified weight drop onto the exposed dura of rats. Animals were divided into two groups. They received a weight drop from two different heights to vary energy transfer to be higher or lower. Animals were sacrificed at 24 hours post injury (1 DPI) or 6 days (6 DPI); brains were frozen and processed for TUNEL (TdT mediated dUTP nick end labelling), light microscopy and immunochemistry.


RESULTS
The total number of TUNEL positive cells was higher in the higher energy group on the first day after the injury. At the same time point, relatively fewer cells were apoptotic than necrotic, while relatively more glial cells than neurons were TUNEL-positive in higher energy trauma. At 6 day after the injury fewer cells were TUNEL positive and there were no longer significant differences between the high and low energy groups.


CONCLUSIONS
Increasing energy transfer in a model for brain contusion demonstrated qualitative and quantitative changes in the pattern of cell death. This complexity must be considered when evaluating brain-protection as treatment results may vary depending on which cellular population and which mechanism of cell death is treated under the exact experimental and clinical conditions.
Lindh
Claes
C
Department of Clinical Neuroscience, Section of Clinical CNS Research, Karolinska Institutet, 171 76 Stockholm, Sweden.
Wennersten
André
A
Arnberg
Fabian
F
Holmin
Staffan
S
Mathiesen
Tiit
T
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001696:Biomechanical Phenomena / Q000502:physiology; D001921:Brain / Q000033:anatomy & histology / Q000473:pathology / Q000503:physiopathology*; D001930:Brain Injuries / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D002452:Cell Count; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D053331:Ectodysplasins / Q000378:metabolism; D004735:Energy Transfer / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D020287:In Situ Nick-End Labeling; D008297:Male; D009336:Necrosis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D009410:Nerve Degeneration / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D015415:Biomarkers; D004268:DNA-Binding Proteins; D053331:Ectodysplasins; C506019:Eda protein, mouse; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins