Resident University of Michigan Ann Arbor, Michigan, United States
Disclosure(s):
Katherine G. Holste, MD: No financial relationships to disclose
Introduction: The pathophysiology of post-hemorrhagic hydrocephalus (PHH) is not well understood, but recent data suggest inflammation plays a significant role. Prior studies found complement cascade inhibition with aurin tricarboxylic acid (ATA) attenuated PHH acutely after intraventricular hemorrhage (IVH). This study aimed to determine the long-term effect of complement inhibition on PHH after IVH.
Methods: Twenty-four young, male rats underwent stereotactically-guided intraventricular injection of either autologous blood co-injected with ATA, autologous blood co-injected with vehicle or saline. All rats underwent MRI on post-hemorrhage day 1, 7, 14, and 28 and were sacrificed on day 28. MRI images were used to calculate ventricular volume and iron accumulation. Open field testing was performed at each timepoint to analyze functional outcomes. Mann-Whitney U tests were performed to determine statistical significance.
Results: Administration of ATA resulted in significantly smaller ventricular volume than vehicle at all time points (day 1 p=0.004; day 7 p= 0.002; day 14 p=0.007; and day 28 p=0.009). Hematoma volumes were smaller in the ATA group compared to vehicle group on day 1 (p= 0.013). Iron accumulation was reduced in the ATA group compared to vehicle at days 7 (p=0.03), 14 (p= 0.18) and 28 (p=0.009). Vehicle rats were significantly less active and less likely to explore their environment than ATA rats 1 month after hemorrhage; vehicles rats spent more time resting (p=0.035), were less likely to cross zones (p=0.003), spent less time in the center of the box (p=0.012), and had less rearing behaviors (p= 0.018).
Conclusion : Complement inhibition was associated with significantly smaller ventricular volume and less iron accumulation after IVH, which was durable 1 month after hemorrhage. Functionally, rats who underwent complement inhibition were more active and more likely to explore their environment. Complement inhibition may be a therapeutic target to attenuate PHH and improve functional outcomes after IVH.
