Delayed tranexamic acid after traumatic brain injury impedes learning and memory: Early tranexamic acid is favorable but not in sham animals.
Publication/Presentation Date
1-1-2024
Abstract
BACKGROUND: Early but not late tranexamic acid (TXA) after TBI preserves blood-brain-barrier integrity, but it is unclear if and how dose timing affects cognitive recovery beyond hours postinjury. We hypothesized that early (1 hour post-TBI) but not late (24 hours post-TBI) TXA administration improves cognitive recovery for 14 days.
METHODS: CD1 male mice (n = 25) were randomized to severe TBI (injury [I], by controlled cortical impact) or sham craniotomy (S) followed by intravenous saline at 1 hour (placebo [P1]) or 30 mg/kg TXA at 1 hour (TXA1) or 24 hours (TXA24). Daily body weights, Garcia Neurological Test scores, brain/lung water content, and Morris water maze exercises quantifying swimming traffic in the platform quadrant (zone [Z] 1) and platform area (Z5) were recorded for up to 14 days.
RESULTS: Among injured groups, I-TXA1 demonstrated fastest weight gain for 14 days and only I-TXA1 showed rapid (day 1) normalization of Garcia Neurological Test ( p = 0.01 vs. I-P1, I-TXA24). In cumulative spatial trials, compared with I-TXA1, I-TXA24 hindered learning (distance to Z5 and % time in Z1, p < 0.05). Compared with I-TXA1, I-TXA24 showed poorer memory with less Z5 time (0.51 vs. 0.16 seconds, p < 0.01) and Z5 crossing frequency. Unexpectedly, TXA in uninjured animals (S-TXA1) displayed faster weight gain but inferior learning and memory.
CONCLUSION: Early TXA appears beneficial for cognitive and behavioral outcomes following TBI, although administration 24 hours postinjury consistently impairs cognitive recovery. Tranexamic acid in sham animals may lead to adverse effects on cognition.
Volume
96
Issue
1
First Page
26
Last Page
34
ISSN
2163-0763
Published In/Presented At
Culkin, M. C., Coons, M., Bele, P., Thaploo, A., Georges, A. P., Anderson, E., Browne, K. D., Jacovides, C., Santos, P., Kaplan, L. J., Meaney, D. F., Smith, D. H., & Pascual, J. L. (2024). Delayed tranexamic acid after traumatic brain injury impedes learning and memory: Early tranexamic acid is favorable but not in sham animals. The journal of trauma and acute care surgery, 96(1), 26–34. https://doi.org/10.1097/TA.0000000000004155
Disciplines
Education | Medical Education
PubMedID
37853567
Department(s)
Department of Education
Document Type
Article