Delayed cognitive deficits can be alleviated by calcium antagonist nimodipine by downregulation of apoptosis following whole brain radiotherapy

Tong,Jing; Li,Juan; Zhang,Qiu‑Shi; Yang,Jian‑Kai; Zhang,Lei; Liu,Hai‑Ying; Liu,Ying‑Zi; Yuan,Jiang‑Wei; Su,Xu‑Ming; Zhang,Xue‑Xin; Jiao,Bao‑Hua

doi:10.3892/ol.2018.8968

Delayed cognitive deficits can be alleviated by calcium antagonist nimodipine by downregulation of apoptosis following whole brain radiotherapy

Authors:
- Jing Tong
- Juan Li
- Qiu‑Shi Zhang
- Jian‑Kai Yang
- Lei Zhang
- Hai‑Ying Liu
- Ying‑Zi Liu
- Jiang‑Wei Yuan
- Xu‑Ming Su
- Xue‑Xin Zhang
- Bao‑Hua Jiao
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Affiliations: Department of Neurosurgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China, Department of Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China, Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China
Published online on: June 13, 2018 https://doi.org/10.3892/ol.2018.8968
Pages: 2525-2532

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Abstract

Radiation therapy is important for the comprehensive treatment of intracranial tumors. However, the molecular mechanisms underlying the pathogenesis of delayed cognitive dysfunction are not well‑defined and effective treatments or prevention measures remain insufficient. In the present study, 60 adult male Wistar rats were randomly divided into three groups, which included a control, whole brain radiotherapy (WBRT) (single dose of 30 Gy of WBRT) and nimodipine (single dose of 30 Gy of WBRT followed by nimodipine injection intraperitoneally) groups. The rats were sacrificed 7 days or 3 months following irradiation. At 3 months, the Morris water maze test was used to assess spatial learning and memory function in rats. The results demonstrated that the WBRT group demonstrated a significantly impaired cognitive performance, decreased numbers of hippocampal Cornu Ammonis (CA)1 neurons and upregulated expression of caspase‑3 in the dentate gyrus compared with those in the control and nimodipine groups. Reverse transcription‑quantitative polymerase chain reaction analysis demonstrated that the WBRT group exhibited increased ratio of B‑cell lymphoma 2 (Bcl‑2)‑associated X protein (Bax)/Bcl‑2 compared with that in control and nimodipine groups on day 7 following irradiation. However, the WBRT group exhibited decreased levels of brain‑derived neurotrophic factor (BDNF) compared with that in control and nimodipine groups at 3 months following brain irradiation. The levels of growth‑associated protein 43 and amyloid precursor protein between the nimodipine group and WBRT group were not statistically significant. The present study demonstrated that neuron apoptosis may lead to delayed cognitive deficits in the hippocampus, in response to radiotherapy. The cognitive impairment may be alleviated in response to a calcium antagonist nimodipine. The molecular mechanisms involved in nimodipine‑mediated protection against cognitive decline may involve the regulation of Bax/Bcl‑2 and BDNF in the hippocampus.

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