Central and Peripheral Secondary Cell Death Processes after Transient Global Ischemia in Nonhuman Primate Cerebellum and Heart

  • Jea-Young Lee
  • Roger Lin
  • Hung Nguyen
  • Eleonora Russo
  • M. Grant Liska
  • Trenton Lippert
  • Yuji Kaneko
  • Cesar V. BorlonganEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1919)


Cerebral ischemia and its pathological sequelae are responsible for severe neurological deficits generally attributed to the neural death within the infarcted tissue and adjacent regions. Distal brain regions, and even peripheral organs, may be subject to more subtle consequences of the primary ischemic event which can initiate parallel disease processes and promote comorbid symptomology. In order to characterize the susceptibility of cerebellar brain regions and the heart to transient global ischemia (TGI) in nonhuman primates (NHP), brain and heart tissues were harvested 6 months post-TGI injury. Immunostaining analysis with unbiased stereology revealed significant cell death in lobule III and IX of the TGI cerebellum when compared to sham cerebellum, coinciding with an increase in inflammatory and apoptotic markers. Cardiac tissue analysis showed similar increases in inflammatory and apoptotic cells within TGI hearts. A progressive inflammatory response and cell death within the cerebellum and heart of chronic TGI NHPs indicate secondary injury processes manifesting both centrally and peripherally. This understanding of distal disease processes of cerebral ischemia underscores the importance of the chronic aberrant inflammatory response and emphasizes the needs for therapeutic options tailored to target these pathways. Here, we discuss the protocols for characterizing the histopathological effects of transient global ischemia in nonhuman primate cerebellum and heart, with an emphasis on the inflammatory and apoptotic cell death processes.

Key words

Secondary injury Neurodegeneration Cell death Purkinje cells Inflammation 


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Jea-Young Lee
    • 1
  • Roger Lin
    • 1
  • Hung Nguyen
    • 1
  • Eleonora Russo
    • 1
  • M. Grant Liska
    • 1
  • Trenton Lippert
    • 1
  • Yuji Kaneko
    • 1
  • Cesar V. Borlongan
    • 1
    Email author
  1. 1.Department of Neurosurgery and Brain Repair, Center of Excellence for Aging and Brain RepairUniversity of South Florida Morsani College of MedicineTampaUSA

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