This interesting paper from China explains how iron accumulation in the hippocampus causes impairment of cognition after hemorrhagic stroke and in the experimental part of the study how iron chelation helps in this problem. Fortunately, ATH has already experimental evidence on how ATH434 can help in many iron overload models.

It is a free paper, here is the abstract:

Redox Biol

. 2024 Feb 13:71:103086.

doi: 10.1016/j.redox.2024.103086. Online ahead of print.

Iron/ROS/Itga3 mediated accelerated depletion of hippocampal neural stem cell pool contributes to cognitive impairment after hemorrhagic stroke

Xuyang Zhang ¹, Huanhuan Li ¹, Haomiao Wang ¹, Qian Zhang ², Xueyun Deng ³, Shuixian Zhang ¹, Long Wang ¹, Chao Guo ¹, Fengchun Zhao ¹, Yi Yin ¹, Tengyuan Zhou ¹, Jun Zhong ¹, Hui Feng ¹, Wei Chen ⁴, Jun Zhang ⁵, Hua Feng ¹, Rong Hu ⁶

Affiliations expand

• PMID: 38367510

DOI: 10.1016/j.redox.2024.103086

Abstract

Hemorrhagic stroke, specifically intracerebral hemorrhage (ICH), has been implicated in the development of persistent cognitive impairment, significantly compromising the quality of life for affected individuals. Nevertheless, the precise underlying mechanism remains elusive. Here, we report for the first time that the accumulation of iron within the hippocampus, distal to the site of ICH in the striatum, is causally linked to the observed cognitive impairment with both clinical patient data and animal model. Both susceptibility-weighted imaging (SWI) and quantitative susceptibility mapping (QSM) demonstrated significant iron accumulation in the hippocampus of ICH patients, which is far from the actual hematoma. Logistical regression analysis and multiple linear regression analysis identified iron level as an independent risk factor with a negative correlation with post-ICH cognitive impairment. Using a mouse model of ICH, we demonstrated that iron accumulation triggers an excessive activation of neural stem cells (NSCs). This overactivation subsequently leads to the depletion of the NSC pool, diminished neurogenesis, and the onset of progressive cognitive dysfunction. Mechanistically, iron accumulation elevated the levels of reactive oxygen species (ROS), which downregulated the expression of Itga3. Notably, pharmacological chelation of iron accumulation or scavenger of aberrant ROS levels, as well as conditionally overexpressed Itga3 in NSCs, remarkably attenuated the exhaustion of NSC pool, abnormal neurogenesis and cognitive decline in the mouse model of ICH. Together, these results provide molecular insights into ICH-induced cognitive impairment, shedding light on the value of maintaining NSC pool in preventing cognitive dysfunction in patients with hemorrhagic stroke or related conditions.