Molecular Neurobiology

, Volume 56, Issue 4, pp 2714–2727 | Cite as

Spatial Dynamics of Vascular and Biochemical Injury in Rat Hippocampus Following Striatal Injury and Aβ Toxicity

  • Zareen AmtulEmail author
  • Carmen Frías
  • Jasmine Randhawa
  • David J. Hill
  • Edith J. Arany


The hippocampus, a brain region vital for memory and learning, is sensitive to the damage caused by ischemic/hypoxic stroke and is one of the main regions affected by Alzheimer’s disease. The pathological changes that might occur in the hippocampus and its connections, because of cerebral injury in a distant brain region, such as the striatum, have not been examined. Therefore, in the present study, we evaluated the combined effects of endothelin-1-induced ischemia (ET1) in the striatum and β-amyloid (Aβ) toxicity on hippocampal pathogenesis, dictated by the anatomical and functional intra- and inter-regional hippocampal connections to the striatum. The hippocampal pathogenesis induced by Aβ or ET1 alone was not severe enough to significantly affect the entire circuit of the hippocampal network. However, the combination of the two pathological states (ET1 + Aβ) led to an exacerbated increase in neuroinflammation, deposition of the amyloid precursor protein (APP) fragments with the associated appearance of degenerating cells, and blood-brain-barrier disruption. This was observed mainly in the hippocampal formation (CA2 and CA3 regions), the dentate gyrus as well as distinct regions with synaptic links to the hippocampus such as entorhinal cortex, thalamus, and basal forebrain. In addition, ET1 + Aβ-treated rats also demonstrated protracted loss of AQP4 depolarization, dissolution of β-dystroglycan, and basement membrane laminin with associated IgG and dysferlin leakage. Spatial dynamics of hippocampal injury in ET1 + Aβ rats may provide a valuable model to study new targets for clinical therapeutic applications, specifically when areas remotely connected to hippocampus are damaged.


Beta-amyloid Ischemia Hippocampus Striatum Blood-brain barrier 



Alzheimer’s disease


amyloid precursor protein







avidin-biotin complex


3,3′-diaminobenzidine tetrahydrochloride


fluorojade B


Funding Information

The funding for this project came from Canadian Institutes of Health Research (R1478A47) and a CIHR Vascular Research fellowship.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Anatomy and Cell BiologyUniversity of Western OntarioLondonCanada
  2. 2.Department of BiologyUniversity of Western OntarioLondonCanada
  3. 3.Departments of Medicine, Physiology and Pharmacology, and PediatricsUniversity of Western OntarioLondonCanada
  4. 4.Lawson Health Research InstituteLondonCanada
  5. 5.Department of Pathology and Laboratory MedicineUniversity of Western OntarioLondonCanada

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