TY - JOUR
T1 - Differences in cell death between high and low energy brain injury in adult rats
AU - Lindh, Claes
AU - Wennersten, André
AU - Arnberg, Fabian
AU - Holmin, Staffan
AU - Mathiesen, Tiit
PY - 2008/12
Y1 - 2008/12
N2 - 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.METHOD: 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.FINDINGS: 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.
AB - 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.METHOD: 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.FINDINGS: 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.
KW - Animals
KW - Apoptosis/physiology
KW - Biomarkers/analysis
KW - Biomechanical Phenomena/physiology
KW - Brain/anatomy & histology
KW - Brain Injuries/complications
KW - Cell Count
KW - DNA-Binding Proteins
KW - Disease Models, Animal
KW - Ectodysplasins/metabolism
KW - Energy Transfer/physiology
KW - Glial Fibrillary Acidic Protein/metabolism
KW - Gliosis/etiology
KW - In Situ Nick-End Labeling
KW - Male
KW - Necrosis/etiology
KW - Nerve Degeneration/etiology
KW - Nerve Tissue Proteins/metabolism
KW - Neurons/metabolism
KW - Nuclear Proteins/metabolism
KW - Rats
KW - Rats, Sprague-Dawley
KW - Time Factors
U2 - 10.1007/s00701-008-0147-7
DO - 10.1007/s00701-008-0147-7
M3 - Journal article
C2 - 19015811
SN - 0001-6268
VL - 150
SP - 1269-75;discussion 1275
JO - Acta Neurochirurgica
JF - Acta Neurochirurgica
IS - 12
ER -