Minocycline attenuates hydrocephalus and inhibits iron accumulation, ependymal damage and epiplexus cell activation after intraventricular hemorrhage in aged rats.

Abstract

Intracerebral hemorrhage is primarily a disease of the elderly and it is frequently accompanied by intraventricular hemorrhage (IVH) which can lead to posthemorrhagic hydrocephalus and poor prognosis. Red blood cell iron has been implicated in brain injury after cerebral hemorrhage. The current study examined using T2* magnetic resonance imaging (MRI) to detect periventricular iron deposition after IVH and investigated the effects of minocycline on hydrocephalus in an aged rat IVH model. It had three parts. In part 1, male aged rats received a 200 μl injection of saline or autologous blood into the lateral ventricle and were euthanized at day 14. In parts 2 and 3, aged IVH rats were treated with vehicle or minocycline and euthanized at day 7 or 14. Rats underwent MRI to quantify hydrocephalus and iron deposition followed by brain histology and immunohistochemistry. Periventricular iron overload was found after IVH using T2* MRI and confirmed by histology. IVH also caused ventricular wall damage and increased the number of CD68(+) choroid plexus epiplexus cells. Minocycline administration reduced iron deposition and ventricular volume at days 7 and 14 after IVH, as well as ventricle wall damage and epiplexus cell activation. In summary, IVH-induced hydrocephalus is associated with periventricular iron deposition, ependymal damage and choroid plexus epiplexus cell activation in aged rats. Minocycline attenuated those effects and might be a potential treatment for posthemorrhagic hydrocephalus in the elderly.

• Authors: Yingfeng Wan, Katherine G Holste, Fenghui Ye, Ya Hua, Richard F Keep, Guohua Xi
• Journal: Experimental neurology (Exp Neurol) Vol. 369 Pg. 114523 (11 2023) ISSN: 1090-2430 [Electronic] United States
• PMID: 37652293 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2023 Elsevier Inc. All rights reserved.

Chemical References

• Minocycline
• Iron

Topics

• Humans
• Rats
• Male
• Animals
• Aged
• Minocycline (pharmacology, therapeutic use)
• Rats, Sprague-Dawley
• Cerebral Hemorrhage (complications, diagnostic imaging, drug therapy)
• Iron
• Hydrocephalus (diagnostic imaging, drug therapy, etiology)