Stroke propensity in the Th3+/ mouse model of β-thalassemia intermedia

Yu Yo Sun*, Hui Wen Yao, Hong Ru Chen, Ching Wen Chen, Melissa M. Kinkaid, Chia Yi Kuan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

β-thalassemia is associated with multiple hematological and cerebrovascular symptoms linked to a hypercoagulable state that has not been fully replicated in animal models for the development of stroke treatments. Herein we compared the physiological properties and responses to transient cerebral hypoxia-ischemia (tHI) between six-month-old wildtype and heterozygous Th3/+ mice, a model of non-transfusion-dependent β-thalassemia intermedia (β-TI). We found that Th3/+ mice developed microcytic anemia, splenomegaly, higher platelet counts, and increased platelet-erythrocyte plus erythrocyte-leukocyte aggregates. Furthermore, Th3/+ mice showed diminished cerebrovascular reactivity (CVR) and cortical oxygen saturation under repetitive hypercapnic challenges. When subjected to a sub-threshold tHI insult, platelets and leukocytes in Th3/+ mice adhered to the cerebrovascular wall or formed aggregates, while their counterparts flew through smoothly in wildtype mice. Subsequently, Th3/+ mice showed increased fibrin deposition around cerebral blood vessels and larger infarction than wildtype mice, especially in female Th3/+ mice. Collectively these results showed that Th3/+ mice mimic key clinical features and a propensity to thromboembolism in β-TI patients. The hypercoagulable state in Th3/+ mice is likely caused by multiple hematological and CVR anomalies that are similar, but are not identical to those in the mouse model of sickle cell anemia. As such, we suggest that Th3/+ mice are a useful model to study the pathological mechanisms and prophylactic stroke treatments in thalassemia patients.

Original languageEnglish
Article number105802
JournalNeurobiology of Disease
Volume171
DOIs
StatePublished - Sep 2022

Keywords

  • Cerebrovascular reactivity
  • Hypoxia-ischemia
  • Post-splenectomy thrombocytosis
  • Silent cerebral infarct

Fingerprint

Dive into the research topics of 'Stroke propensity in the Th3+/ mouse model of β-thalassemia intermedia'. Together they form a unique fingerprint.

Cite this