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Investigations on Alterations of Hippocampal Circuit Function Following Mild Traumatic Brain Injury
Published on: November 19, 2012
Age does not influence DNA fragmentation in the hippocampus after fatal traumatic brain injury in young and aged
J Fowler1, M A MacKinnon, R Raghupathi
1University Department of Neuropathology, South Glasgow University Hospitals NHS Trust, Southern General Hospital, UK.
Insights
DNA fragmentation in the hippocampus of pediatric and adult traumatic brain injury patients showed similar patterns, suggesting age is not a key factor in outcome differences.
Area of Science:
- Neuroscience
- Pathology
- Cell Biology
Background:
- Traumatic brain injury (TBI) can cause significant neuronal damage.
- Understanding age-related differences in TBI response is crucial for predicting outcomes.
- DNA fragmentation is a marker of cell death following injury.
Purpose of the Study:
- To investigate and compare in-situ DNA fragmentation in the hippocampus of pediatric and adult TBI patients.
- To determine if age influences the pattern or extent of DNA fragmentation after TBI.
- To correlate DNA fragmentation with neuronal damage and cell types.
Main Methods:
- Terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nick end labeling (TUNEL) technique was used on hippocampal paraffin sections.
- Patients were divided into two age groups: pediatric (4-12 years) and adult (64-89 years), with age-matched controls.
- Immunohistochemistry for astrocytes (GFAP) and macrophages (CD68), H&E, and Luxol Fast Blue/Cresyl Violet staining were employed for lesion characterization.
Main Results:
- Both apoptotic (Type II) and non-apoptotic (Type I) TUNEL-positive cells were observed.
- Type II TUNEL-positive cells were predominantly in white matter, comprising <1% of total TUNEL-positive cells.
- Overall, DNA fragmentation patterns in the hippocampus were similar between pediatric and adult TBI patients and controls, with some exceptions in specific hippocampal sectors in older adults.
Conclusions:
- The distribution and amount of DNA fragmentation in the hippocampus are comparable in children and adults following TBI.
- Hippocampal DNA fragmentation does not appear to be an independent variable explaining outcome differences based on age after childhood TBI.
- Observed TUNEL-positive cells in grey matter often exhibited morphology consistent with necrosis and selective neuronal damage.
Abstract:
Paraffin sections from the hippocampus of 12 head-injured patients (Group A, aged between 4 and 12 years n = 6 and Group B, aged between 64 and 89 years n = 6) and associated age-matched controls were stained by the terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nick end labeling (TUNEL) technique for evidence of in-situ DNA fragmentation. TUNEL+ cells were of 2 Types: I (non-apoptotic) and II (apoptotic). In addition sections stained H&E, combined Luxol Fast Blue/Cresyl Violet and by immunohistochemistry for astrocytes (GFAP) and macrophages (CD68) were used to characterize the lesions. Small numbers of Type I TUNEL+ cells were seen in all sectors of the hippocampus except CA2 of both Groups A and B. Type II TUNEL+ cells were mainly found in the white matter. They constituted less than 1% of all TUNEL+ cells. There were similar or fewer TUNEL+ cells in the corresponding areas in the controls compared with the head-injured patients. However, in the dentate fascia and the CA4 sector of the Group B cases, larger numbers of TUNEL+ cells were seen in controls than after trauma. In the grey matter most TUNEL+ cells had the morphology ofnecrosis that corresponded with foci of selective neuronal damage. Only a few TUNEL+ cells were seen in white matter. The occasional Type I TUNEL+ cells were seen in grey matter. It is concluded that the amount and distribution of DNA fragmentation in children and adults is similar and therefore at least in the hippocampus does not provide an explanation for age as an independent variable of outcome after traumatic brain injury in childhood.
