Molecular Neurobiology

, Volume 55, Issue 5, pp 4225–4239 | Cite as

Apoptosis Following Cortical Spreading Depression in Juvenile Rats

  • Ali Jahanbazi Jahan-Abad
  • Leila Alizadeh
  • Sajad Sahab Negah
  • Parastoo Barati
  • Maryam Khaleghi Ghadiri
  • Sven G. Meuth
  • Stjepana Kovac
  • Ali Gorji


Repetitive cortical spreading depression (CSD) can lead to cell death in immature brain tissue. Caspases are involved in neuronal cell death in several CSD-related neurological disorders, such as stroke and epilepsy. Yet, whether repetitive CSD itself can induce caspase activation in adult or juvenile tissue remains unknown. Inducing repetitive CSD in somatosensory cortices of juvenile and adult rats in vivo, we thus aimed to investigate the effect of repetitive CSD on the expression caspase-3, caspase-8, caspase-9, and caspase-12 in different brain regions using immunohistochemistry and western blotting techniques. Higher numbers of dark neurons and TUNEL-positive cells were observed in the hippocampal CA1 and CA3 regions as well as in the entorhinal and somatosensory cortices after CSD in juvenile rats. This was accompanied by higher expressions of caspase-3, caspase-8, and caspase-9. Caspase-12 levels remained unchanged after CSD, suggesting that endoplasmic reticulum stress is not involved in CSD-triggered apoptosis. Changes in caspase expression were paralleled by a decrease of procaspase-3, procaspase-8, and procaspase-9 in juvenile rat brain tissue subjected to CSD. In contrast, repetitive CSD in adult rats did not result in the upregulation of caspase signaling. Our data points to a maturation-dependent vulnerability of brain tissue to repetitive CSD with a higher degree of apoptotic damage and caspase upregulation observed in juvenile tissue. Findings suggest a key role of caspase signaling in CSD-induced cell death in the immature brain. This implies that anti-apoptotic treatment may prevent CSD-related functional deficits in the immature brain.


Spreading depolarization Cell injury Developing brain Migraine Stroke Epilepsy 



This study was supported by the Iran National Science Foundation (INSF) to AG.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Shefa Neuroscience Research CenterKhatam Alanbia HospitalTehranIran
  2. 2.Department of NeuroscienceMashhad University of Medical SciencesMashhadIran
  3. 3.Department of NeurosurgeryWestfälische Wilhelms-Universität MünsterMünsterGermany
  4. 4.Department of NeurologyWestfälische Wilhelms-Universität MünsterMünsterGermany
  5. 5.Epilepsy Research CenterWestfälische Wilhelms-Universität MünsterMünsterGermany

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