College
Rowan-Virtua School of Osteopathic Medicine
Keywords
Traumatic Brain Injury, Anticoagulant, Dementia, microgliosis, neurology. autoinflammation
IRB or IACUC Protocol Number
tissue samples only, provided by Penn
Date of Presentation
5-1-2025 12:00 AM
Poster Abstract
Objective:
The study objective was to investigate the acute anti-inflammatory effects of dabigatran in a preclinical mouse controlled cortical impact (CCI) model of severe traumatic brain injury (TBI).
Design
Mice were separated into three groups: controlled cortical impact (CCI) with dabigatran (drug treatment, n=5), CCI with saline (positive control, n=5), and sham CCI without saline or dabigatran (negative control, n=3). Dabigatran (80mg/kg) or saline was administered orally at 2, 10, 18, 26, 34, and 42 hours following experimental CCI in the drug treatment or positive control groups, respectively. Animals in the negative control group received sham CCI only. 48h following CCI or sham CCI, mice were euthanized via transcardial perfusion. Brains were processed for immunohistochemistry (IHC) assessment. IHC was performed for both IBA-1 and IgG. Immunoreactivity was quantified using a Leica Aperio ScanScope and Leica’s image analysis color deconvolution tool. Percent Total Positive (PTP) immunoreactivity was calculated and used for analysis.
Results
We observed a statistically significant difference in IBA-1 microglial immunoreactivity amongst the three experimental groups (p=0.006), with an increase in IBA-1 immunoreactivity in the positive control group compared to the negative control group (p=0.008) and a decrease in IBA-1 immunoreactivity in the drug treatment group compared to the positive control group (p=0.019). There was no observed difference in IBA-1 immunoreactivity between the drug treatment and negative control groups (p=0.623).
We observed a statistically significant difference in intraparenchymal IgG immunoreactivity amongst the three experimental groups (p=0.001), with an increase in IgG immunoreactivity in both the positive control group and the drug treatment group compared to the negative control group (p=0.004 and p=0.001, respectively). There was no observed difference in IgG immunoreactivity between the drug treatment and positive treatment groups (p=0.426).
Conclusion
Our results suggest that dabigatran reduces brain intraparenchymal microgliosis without significantly increasing BBB pathology in a preclinical model of severe TBI.
Disciplines
Heterocyclic Compounds | Medical Neurobiology | Medicinal Chemistry and Pharmaceutics | Medicine and Health Sciences | Neurology | Neuroscience and Neurobiology | Neurosciences
Included in
Heterocyclic Compounds Commons, Medical Neurobiology Commons, Medicinal Chemistry and Pharmaceutics Commons, Neurology Commons, Neuroscience and Neurobiology Commons, Neurosciences Commons
Dabigatran Reduced Acute Microgliosis in a Mouse Model with TBI
Objective:
The study objective was to investigate the acute anti-inflammatory effects of dabigatran in a preclinical mouse controlled cortical impact (CCI) model of severe traumatic brain injury (TBI).
Design
Mice were separated into three groups: controlled cortical impact (CCI) with dabigatran (drug treatment, n=5), CCI with saline (positive control, n=5), and sham CCI without saline or dabigatran (negative control, n=3). Dabigatran (80mg/kg) or saline was administered orally at 2, 10, 18, 26, 34, and 42 hours following experimental CCI in the drug treatment or positive control groups, respectively. Animals in the negative control group received sham CCI only. 48h following CCI or sham CCI, mice were euthanized via transcardial perfusion. Brains were processed for immunohistochemistry (IHC) assessment. IHC was performed for both IBA-1 and IgG. Immunoreactivity was quantified using a Leica Aperio ScanScope and Leica’s image analysis color deconvolution tool. Percent Total Positive (PTP) immunoreactivity was calculated and used for analysis.
Results
We observed a statistically significant difference in IBA-1 microglial immunoreactivity amongst the three experimental groups (p=0.006), with an increase in IBA-1 immunoreactivity in the positive control group compared to the negative control group (p=0.008) and a decrease in IBA-1 immunoreactivity in the drug treatment group compared to the positive control group (p=0.019). There was no observed difference in IBA-1 immunoreactivity between the drug treatment and negative control groups (p=0.623).
We observed a statistically significant difference in intraparenchymal IgG immunoreactivity amongst the three experimental groups (p=0.001), with an increase in IgG immunoreactivity in both the positive control group and the drug treatment group compared to the negative control group (p=0.004 and p=0.001, respectively). There was no observed difference in IgG immunoreactivity between the drug treatment and positive treatment groups (p=0.426).
Conclusion
Our results suggest that dabigatran reduces brain intraparenchymal microgliosis without significantly increasing BBB pathology in a preclinical model of severe TBI.
