Iranian Journal of Basic Medical Sciences

Iranian Journal of Basic Medical Sciences

Spreading depression induces age- and caspase-specific patterns of neuronal injury in the rat brain

Articles in Press

Document Type : Original Article

Authors
Arezo Eshaghabadi Niasari 1
NoorMohammad Meshkinkhood 1
Hasan Hosseini Ravandi 1
Sayed Mostafa Modarres Mousavi 1
Fatemeh Alipour 1
Sven G Meuth 2
Maryam Khaleghi Ghadiri 3
Ali Gorji 3, 4, 5
1 Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran
2 Department of Neurology, University of Münster, Münster, Germany
3 Department of Neurosurgery, University of Münster, Münster, Germany
4 Epilepsy Research Center, University of Münster, Münster, Germany
5 Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
10.22038/ijbms.2026.96886.20837
Abstract
Objective(s): To determine whether repetitive spreading depression (SD) induces neuronal injury and caspase-related apoptotic changes and to compare these effects between juvenile and adult rats.
Materials and Methods: Repetitive SD was induced in the somatosensory cortex of juvenile and adult Wistar rats. Neuronal injury and apoptosis were assessed by histology and TUNEL staining, while caspases 3, 8, 9, and 12 were evaluated by immunohistochemistry and Western blotting in neocortical and hippocampal tissues.
Results: Repetitive SD induced greater neuronal injury and DNA fragmentation in juvenile than adult rats, as indicated by increased dark neuron formation and TUNEL-positive cells. Caspase immunoreactivity showed age- and region-specific changes, with greater caspase-related immunoreactivity in the hippocampal and neocortical tissues of juvenile rats. In contrast, Western blot analysis showed decreased caspase-8 and caspase-9 protein levels, highlighting differences between tissue immunoreactivity and total protein expression. Caspase-12 immunoreactivity and protein levels showed no significant differences between SD and sham groups in either age group.
Conclusion: Repetitive SD induces age-, region-, and caspase-specific patterns of neuronal injury and apoptosis, with the developing brain showing greater susceptibility. The differential caspase findings suggest complex regulation of apoptotic pathways following repetitive SD and warrant further mechanistic investigation.
Keywords
Developing brain
Neocortex
Neuroprotection
Programmed cell death
Subarachnoid hemorrhage
Subjects
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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 15 November 2026