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Temporal and spatial profile of Bid cleavage after experimental traumatic brain injury
Gerhard Franz1, Ronny Beer, Denis Intemann
1Department of Neurology, University Hospital Innsbruck, Austria.
Abstract:
Apoptosis plays an essential role in the cascade of CNS cell degeneration after traumatic brain injury. However, the underlying mechanisms are poorly understood. The authors examined the temporal profile and cell subtype distribution of the proapoptotic protein Bid from 6 hours to 7 days after cortical impact injury in the rat. Increased protein levels of tBid were seen in the cortex ipsilateral to the injury site from 6 hours to 3 days after trauma. Immunohistologic examinations revealed expression of tBid in neurons, astrocytes, and oligodendrocytes from 6 hours to 3 days after impact injury, and concurrent assessment of DNA damage using TUNEL identified tBid-immunopositive cells with apoptoticlike morphology in the traumatized cortex. Moreover, Bid cleavage and activation of caspase-8 and caspase-9 occurred at similar time points and in similar brain regions (i.e., cortical layers 2 to 5) after impact injury. In contrast, there was no evidence of caspase-8 or caspase-9 processing or Bid cleavage in the ipsilateral hippocampus, contralateral cortex, and hippocampus up to 7 days after the injury. The results provide the first evidence of Bid cleavage in the traumatized cortex after experimental traumatic brain injury in vivo, and demonstrate that tBid is expressed in neurons and glial cells. Further, findings indicate that cleavage of Bid may be associated with the activation of the initiator caspase-8 and caspase-9. Finally, these data support the hypothesis that cleavage of Bid contributes to the apoptotic degeneration of different CNS cells in the injured cortex.
Insights
Traumatic brain injury triggers apoptosis in CNS cells. This study shows that the protein Bid is cleaved in neurons and glial cells in the injured cortex, contributing to cell death.
Area of Science:
- Neuroscience
- Cell Biology
- Traumatic Brain Injury Research
Background:
- Apoptosis is crucial in central nervous system (CNS) cell degeneration post-traumatic brain injury (TBI).
- Mechanisms driving TBI-induced apoptosis remain unclear.
Purpose of the Study:
- To investigate the temporal profile and cell-specific expression of the proapoptotic protein Bid after experimental TBI.
- To determine if Bid cleavage correlates with caspase activation in the injured brain.
Main Methods:
- Cortical impact injury was induced in rats.
- Temporal protein levels of Bid (tBid) were analyzed from 6 hours to 7 days post-injury.
- Immunohistology identified tBid-expressing cell subtypes (neurons, astrocytes, oligodendrocytes).
- DNA damage (TUNEL assay) and caspase-8/caspase-9 activation were assessed in specific brain regions.
Main Results:
- Increased tBid levels were detected in the injured cortex from 6 hours to 3 days post-trauma.
- tBid expression was observed in neurons, astrocytes, and oligodendrocytes within the traumatized cortex.
- Bid cleavage, caspase-8, and caspase-9 activation occurred in cortical layers 2-5 post-injury.
- No Bid cleavage or caspase activation was found in non-injured brain regions.
Conclusions:
- This study provides the first in vivo evidence of Bid cleavage in the cortex following experimental TBI.
- Cleavage of Bid occurs in various CNS cell types within the injured cortex.
- Bid cleavage is linked to the activation of initiator caspases (caspase-8 and -9), suggesting its role in TBI-induced apoptosis.