Preliminary Experimental Study Of Minocycline Improves Radiation-induced Cognitive Impairment And Its Mechanisms

Objective: As an important treatment modality for head and neck tumor patients,cranial radiotherapy causes a debilitating cognitive decline thus decreasing the quality ofpatients’ life, and intense investigation is being carried out to look for effective ways toovercome this side effect. The objective of this study was to investigate whetherminocycline, an antibiotic that has demonstrated neuroprotective properties in a variety ofexperimental models of neurological diseases, has protective effects on radiation-induceddamage in hippocampus and cognitive decline.Methods:118male Sprague-Dawley rats one month old were divided into six groups,including control, minocycline only, anesthesia control, anesthesia minus minocycline,irradiation and irradiation minus minocycline. Minocycline fed by90mg/kg before and45mg/kg daily after irradiation. Single20Gy whole brain irradiation (WBI) was given using4MeV electron beams.22rats were decapitated for measuring the level of apoptosis inhippocampal neurons3-12hours post WBI using immunohisto-chemistry for NeuN/Casp-3and DCX/Casp-3. One month after WBI,18rats was injected with5-Bromodeoxyuridine(BrdU)(50mg/kg·d,6days). The deficit of spatial learning and memory of rats (allremaining96rats) caused by WBI was assessed using the Morris water maze and openfield test two months after WBI. After all tests, neurogenesis post WBI was determined byusing immunohistochemistry for BrdU/NeuN.Results: Our results show that compared with the sham-irradiated controls andirradiation minus minocycline groups, WBI caused a significant working memory lossmanifest as longer latency to reach the hidden platform in the Morris water maze task (P <0.05). And there was no differences between the controls and irradiation minus minocycline groups (P>0.05). While WBI induced massive apoptosis in new neurons ofhippocampus3hours (DCX+/Casp-3+cells)(P <0.05) post irradiation, minocyclineintervention significantly protected new neurons from radiation-induced apoptosis6hoursafter WBI, thereby resulting in reducing75%(P <0.05) of new neuron depletion. Twomonths after receiving a dose of20Gy of radiation, the rats show a significant decline inBrdU+/NeuN+neurons (P <0.05), and minocycline intervention does not make anyimprovement (P>0.05).Conclusions: Taken all together, minocycline significantly protects new neurons fromradiation-induced apoptosis, leading to less new neuron loss and partially improves thecognitive impairment of young rats post WBI. The results indicate a potential clinicalimplication of minocycline as an effective adjunct in radiotherapy for brain tumor patients.