Iranian Journal of Basic Medical Sciences

Iranian Journal of Basic Medical Sciences

Histological and molecular analysis of cerebellar regeneration in zebrafish (Danio rerio): Correlation of inflammatory response with activation of developmental pathways

Articles in Press

Document Type : Original Article

Authors
Javid Rezaei Lord 1
Tahereh Foroutan 1
Tooba Mirzapour 2
1 Department of Animal Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran
2 Department of Biology, Faculty of Basic Sciences, University of Guilan, Rasht, Iran
10.22038/ijbms.2026.95573.20604
Abstract
Objective(s): This study aimed to characterize the temporal relationship among inflammatory responses, developmental gene reactivation, and structural restoration during cerebellar regeneration after mechanical injury in adult zebrafish.
Materials and Methods: A focal cerebellar lesion was induced in 300 adult zebrafish using a stereotaxic approach with a 30-gauge needle. Histological analyses were performed at 1, 7, 14, 21, and 28 days post-injury (dpi) using hematoxylin and eosin staining. Quantitative RT-PCR was used to assess the expression of inflammatory genes (tnf-α, il-1β, and il-10) and regeneration-associated genes (shha, pax5, neurod, slc17a7a, ca8, and aldoca) at defined post-injury intervals.
Results: Histological examination revealed severe tissue disruption and inflammatory cell infiltration at 1 dpi, followed by progressive reorganization of cerebellar architecture by 28 dpi. Expression of tnf-α and il-1β increased transiently during the acute phase, peaking at 18-24 hr post-injury before returning to basal levels. In contrast, il-10 showed a delayed but robust induction, reaching maximal expression at 18 hr and remaining elevated during the resolution phase. Developmental and neurogenic genes displayed distinct temporal profiles: shha and neurod peaked at 7 dpi; pax5 and slc17a7a reached maximal expression at 14 dpi; whereas aldoca showed the strongest early induction. Quantitative analysis further confirmed a significant reduction in lesion size throughout the regeneration period.
Conclusion: Zebrafish cerebellar regeneration involves a coordinated sequence of inflammatory, developmental, and neurogenic events. The temporal integration of immune modulation with reactivation of developmental pathways appears to be essential for successful restoration and provides insights into strategies for neural repair in vertebrates.
Keywords
Cerebellum
Gene Expression
Inflammation
Neural Stem Cell
Neurogenesis
Regeneration
Zebrafish
Subjects
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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 17 October 2026