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

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.

Fractionated brain irradiation profoundly reduces hippocampal immature neuron numbers without affecting spontaneous behavior and cognition in mice

“…Overall, whereas effects of WBRT on neurobiology seem clear and robust, the results from cognitive studies using WBRT in rodents are inconclusive. Some studies failed to detect changes in spatial memory (mainly Morris water maze) upon irradiation 23,24,36,37 , however, others could find changes 25,[38][39][40][41][42][43][44] . Some interesting observations were made with respect to (1) the use of deviating spatial strategies in spatial memory tasks by irradiated animals 45 , (2) enhanced extinction of memory upon irradiation and…”

Substantiated therapy of pre-dementia cognitive impairment with calcium-channel blockers

“…Нейропротективный эффект нимодипина подтвержден также в исследованиях, изучавших эффективность превентивного применения нимодипина в развитии послеоперационной когнитивной дисфункции у старых крыс [37,38]. В сравнительно недавно опубликованных работах показано, что применение комбинированной 2023;17(3): [38][39][40][41][42][43] терапии нимодипином совместно с акупунктурой у пациентов с легкими когнитивными нарушениями после ишемического инсульта [39] и нимодипином в комбинации с розувастатином у пациентов с болезнью мелких сосудов показало лучший результат в отношении улучшения когнитивных функций в сравнении с монотерапией [40]. Полученные данные подчеркивают преимущества комплексного подхода в лечении пациентов с додементными когнитивными нарушениями, включаю щего коррекцию факторов риска, этиотропную и патогенетическую терапию.…”

“…Полученные данные подчеркивают преимущества комплексного подхода в лечении пациентов с додементными когнитивными нарушениями, включаю щего коррекцию факторов риска, этиотропную и патогенетическую терапию. Важным открытием явилась способность нимодипина предотвращать развитие когнитивных нарушений после облучения головного мозга [41]. Лучевая терапия, как известно, используется в комплексном лечении опухолей головного мозга, но часто дает осложнения в виде когнитивного снижения, молекулярные механизмы развития которого четко не определены.…”

Efficacy of Nimodipine Combined with Latanoprost in Treating Open-Angle Glaucoma and Its Influence on Ocular Hemodynamics and Visual Field Defects

“…In recent years, some scholars have found that nimodipine also has a certain protective effect on retinal ganglion cells. 8 , 9 However, there are relatively few reports on the treatment of open-angle glaucoma with nimodipine combined with latanoprost.…”