Despite years of effort, no effective acute phase treatment has been discovered for traumatic brain injury. One impediment to successful drug development is entangled secondary injury pathways. Here we show that protein S, a natural multifunctional protein that regulates coagulation, inflammation, and apoptosis, is able to reduce the extent of multiple secondary injuries in traumatic brain injury, and therefore improve prognosis. Mice subjected to controlled cortical impact were treated acutely (10-15 minutes post-injury) with a single dose of either protein S (1 mg/kg) or vehicle phosphate buffered saline via intravenous injection. At 24 hours post-injury, compared to the non-treated group, the protein S treated group showed substantial improvement of edema and fine motor coordination, as well as mitigation of progressive tissue loss. Immunohistochemistry and western blot targeting caspase-3, B-cell lymphoma 2 (Bcl-2) along with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay revealed that apoptosis was suppressed in treated animals. Immunohistochemistry targeting CD11b showed limited leukocyte infiltration in the protein S-treated group. Moreover, protein S treatment increased the ipsilesional expression of aquaporin-4, which may be the underlying mechanism of its function in reducing edema. These results indicate that immediate intravenous protein S treatment after controlled cortical impact is beneficial to traumatic brain injury prognosis. Animal Use Protocols (AUPs) were approved by the University Committee on Animal Resources (UCAR) of University of Rochester Medical Center (approval No. UCAR-2008-102R) on November 12, 2013.
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http://dx.doi.org/10.4103/1673-5374.282258 | DOI Listing |
Intensive Care Med
January 2025
Global Health Research Group in Acquired Brain and Spine Injuries, Cambridge, UK.
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January 2025
Diabetes, Endocrinology and Metabolism Division, Department of Medicine, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA.
Introduction: Traumatic brain injury (TBI) is a significant health issue among veterans and poses a substantial risk for pituitary injury. Consensus guidelines recommend that patients who have sustained a TBI should undergo a baseline pituitary hormonal evaluation after the primary brain insult. Patients with abnormal screening test results or with symptoms of hypopituitarism should be referred to endocrinology for a full assessment.
View Article and Find Full Text PDFJ Neurotrauma
January 2025
Department of Anaesthesia and Intensive Care, Centre Hospitalier Universitaire Grenoble, and Inserm, U1216, Grenoble Institut Neurosciences, University Grenoble Alpes, Grenoble, France.
The effect of sex in outcomes after severe traumatic brain injury (TBI) remains uncertain. We explored whether outcomes differed between women and men after standardized care management during the first 5 days in the intensive care unit (ICU). This study was an observational analysis of the OXY-TC multicenter randomized clinical trial between June 15, 2016 and April 17, 2021.
View Article and Find Full Text PDFJ Alzheimers Dis
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Division of Neurosurgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei.
Although the association between dementia such as Alzheimer's disease and traumatic brain injury (TBI) is well established, there are significant knowledge gaps with respect to the perspective of dementia and epilepsy without TBI. We aimed to investigate the relationship between dementia and epilepsy in a population-based study of patients without history of TBI. This study included a random sample of 30,715 patients with no history of TBI, including 6143 with epilepsy as the study cohort and 24,572 without epilepsy as the comparison cohort.
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