Current Neurovascular Research

Prof. Kenneth Maiese
Neurology and Neurosciences UMDNJ
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Sublethal Total Body Irradiation Leads to Early Cerebellar Damage and Oxidative Stress

Author(s): Li Cui, Dwight Pierce, Kim E. Light, Russell B. Melchert, Qiang Fu, K. Sree Kumar and Martin Hauer-Jensen

Affiliation: Department of Pharmaceutical Sciences, Division of Radiation Health, UAMS College of Pharmacy, 4301 W. Markham St., Ȋ-3, Little Rock, AR 72205, USA.

Keywords: Calcium, cerebellum, inflammatory response, oxidative stress, Purkinje cell, sublethal radiation

Abstract:

The present study aimed at identifying early damage index in the cerebellum following total body irradiation (TBI). Adult male CD2F1 mice (n=18) with or without TBI challenge (8.5 Gy irradiation) were assessed for histology and expression of selected immunohistochemical markers including malondiadehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHdG), protein 53 (p53), vascular endothelial growth factor receptor 2 (VEGF-R2), CD45, calbindin D-28k (CB-28) and vesicular glutamate transport-2 (VGLUT2) in cerebellar folia II to IV. Compared to sham-controls, TBI significantly increased vacuolization of the molecular layer. At high magnification, deformed fiber-like structures were found along with the empty matrix space. Necrotic Purkinje cells were identified on 3.5 days after TBI, but not on 1 day. Purkinje cell count was reduced significantly 3.5 days after TBI. Compared with sham control, overall intensities of MDA and 8-OHdG immunoreactivities were increased dramatically on 1 and 3.5 days after TBI. Expression of VEGF-R2 was identified to be co-localized with 8-OHdG after TBI. This validates microvessel endothelial damage. The p53 immunoreactivities mainly deposited in the granular layer and microvessels after TBI and co-localization of the p53 with the CD45, both which were found within the microvessels. After TBI, CB28 expression decreased whereas the VGLUT2 expression increased significantly; Purkinje cells exhibited a reduced body size and deformity of dendritic arbor, delineated by CB28 immunoreactivity. Substantial damage to the cerebellum can be detectable as early as 1- 3.5 days in adult animals following sublethal TBI. Oxidative stress, inflammatory response and calcium neurotoxicity-associated mechanisms are involved in radiation-induced neuronal damage.

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Article Details

VOLUME: 7
ISSUE: 2
Page: [125 - 135]
Pages: 11
DOI: 10.2174/156720210791184880