An experimental study on the ameliorating effect of terazosin on whole‐brain irradiation‐induced cognitive dysfunction
Ma Jiayan1, Zhu Xueting2, Yang Hongying3, Zhang Liyuan4
1Department of Experimental Center, Second Affiliated Hospital of Soochow University, Suzhou 215004, China; 2Department of Radiotherapy and Oncology, Affiliated People's Hospital of Jiangsu University, Zhenjiang 212002, China; 3School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, China; 4Department of Radiotherapy and Oncology, Laboratory for Combined Radiotherapy and Immunotherapy of Cancer, Second Affiliated Hospital of Soochow University/Suzhou Key Laboratory for Combined Radiotherapy and Immunotherapy of Cancer, Suzhou 215004, China
Abstract：Objective To verify the protective effect of terazosin on cognitive function of rats after whole-brain irradiation (WBI) and to investigate its mechanism. Methods A total of 64 1-month-old male SD rats were randomly divided into the untreated control group, terazosin group, irradiation group and irradiation plus terazosin group (combination group). WBI was administered at a single dose of 20 Gy in the irradiation and combination groups. The open field test and the Morris water maze (MWM) test were used to evaluate the effect of terazosin on cognitive function after WBI.Starting from the three aspects of juvenile neuron apoptosis, neurogenesis disorderand microglia activation, the possible cellular mechanism wasassayed by double-label immunofluorescence staining for BrdU (bromodeoxyuridine) / NeuN, DCX(Doublecortin) / Caspase-3 and single-label immunofluorescence staining for Iba-1 (ionized calcium binding adaptor molecule-1). Results Terazosin intervention improved the short-term memory retention of irradiated rats (P=0.032). After terazosin treatment, the number of DCX+ cells in the combination groupwas increased by approximately 35% compared with that in the irradiation group (P=0.038). The number of BrdU+/NeuN+ cells in the combination group was increased by approximately 15% than that in the irradiation group (P>0.05). The number of Iba-1+ cells in the irradiation plus terazosin group was decreased by 49% compared with that in the irradiation group (P=0.036). Conclusion Terazosin may reduce the hippocampal juvenile neuron loss and inhibit neuroinflammation via microglia activation, which can alleviate WBI-induced cognitive dysfunction to a certain extent.
Ma Jiayan,Zhu Xueting,Yang Hongying et al. An experimental study on the ameliorating effect of terazosin on whole‐brain irradiation‐induced cognitive dysfunction[J]. Chinese Journal of Radiation Oncology, 2022, 31(11): 1034-1038.
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