Abstract TP119: Tibia Fracture Leads to Long-Lasting Memory Dysfunction in Mice Through Enhanced Blood-Brain Barrie Breakdown in the Hippocampus and White Matter Damage

Abstract

Background and Purpose: Tibia fracture (BF) causes long-lasting memory dysfunction in stroke mice, which is associated with microglia accumulation in the hippocampus ipsilateral to the stroke injury. The underlying mechanism is unclear. Hypothesis: BF exacerbates blood brain barrier (BBB) breakdown and fibrin extravasation in the hippocampus enhancing white matter damage of stroke mice. Method: C57 mice (8-weeks) were randomly assigned to BF, stroke (pMCAO), BF+stroke (BF 6h before stroke) and sham groups. The integrity of BBB, fibrin deposition and CD68 + cells infiltration in the hippocampus were analyzed 3 days and the white matter injury in the basal ganglia was analyzed 8 weeks after the surgeries. Results: Compared to BF group, stroke and BF+stroke groups had lower level of claudin-5, fewer pericytes, more extravascular fibrin and CD68 + cells in the ipsilateral side of stroke 3 days after the injuries. BF+stroke group had the lowest level of claudin-5, fewest pericytes, highest extravascular fibrin and most CD68 + cells among the three groups. BF+stroke group also had a lower level of claudin-5 and fewer CD13 + pericytes in the contralateral side than the other two groups. Compared to sham group, the white matter bundle areas in the basal ganglia were reduced in stroke and BF+stroke groups in both contralateral and ipsilateral sides 8 weeks after the injuries. Stroke and BF+stroke groups also has smaller white matter bundle areas in the ipsilateral than contralateral side, and the white matter bundle areas in the contralateral side of BF+stroke group were also smaller than stroke group. Conclusion: BF shortly before stroke causes long-lasting memory dysfunction in mice through enhancing BBB breakdown and fibrin extravasation in the hippocampus, which exacerbates neuroinflammation and white matter damage.