ABSTRACT
Radiation-induced brain injury (RBI) is a common long-term complication of radiotherapy for nasopharyngeal carcinoma (NPC) and seriously affects the quality of life and overall survival of patients. In the era of intensity-modulated radiation therapy (IMRT), the long-term complications after radiotherapy, especially RBI, are becoming increasingly concerning because a number of treated patients with NPC obtain long-term survival. At present, the understanding of RBI is still being explored, and its pathogenesis and treatment methods are continuously updated. This article reviews the research progress of RBI in patients with NPC.
ABSTRACT
Objective:To investigate the effects of Bifidobacterium animalis subsp. lactis BB-12 on hippocampal neuroinflammation and cognitive function of mice after whole brain radiotherapy. Methods:A total of sixty male C57BL/6J mice aged 7-8 weeks were randomly divided into 5 groups with 12 mice in each group: control group (Con group), probiotic group (BB-12 group), irradiation group (IR group), irradiation and Memantine group (IR+ Memantine group), irradiation and probiotic group (IR+ BB-12 group). The model of radiation-induced brain injury of mice was established by 10 Gy whole brain radiotherapy with a medical linear accelerator. Y-maze test was used to evaluate the cognitive function. The activation of microglia and astrocytes was observed by immunofluorescence staining. The expressions of inflammatory cytokines interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) were detected by quantitative real-time reverse transcription polymerase chain reaction (QRT-PCR) and Western blot.Results:Y-maze test showed that, compared with Con group, the percentage of the times of reaching the novel arm in the total times of the three arms decreased significantly in the IR group ( t=5.04, P<0.05). BB-12 mitigated radiation-induced cognitive dysfunction ( t=4.72, P<0.05). Compared with Con group, the number ( t=3.05, 7.18, P<0.05) and circularity index ( t=6.23, 2.52, P<0.05) of Iba1 and GFAP positive cells were increased, the microglia and astrocytes were activated in the hippocampus of IR group, but these alterations were eliminated by BB-12. After whole brain IR, the mRNA and protein expression levels of inflammatory cytokines IL-1β, IL-6 and TNF-α in the hippocampus of mice were significantly increased compared with Con group ( tmRNA =4.10, 3.04, 4.18, P<0.05; tprotein=11.49, 7.04, 8.42, P<0.05), which were also significantly reduced by BB-12 compared with IR group ( tmRNA=4.20, 3.40, 2.84, P<0.05; tprotein=6.36, 4.03, 3.75, P<0.05). Conclusions:Bifidobacterium animalis BB-12 can suppress neuroinflammation mediated by microglia and astrocytes in the hippocampus of mice after radiotherapy and alleviates IR-induced cognitive dysfunction. Therefore, BB-12 has potential application in alleviating radiation induced brain injury.
ABSTRACT
Radiation-induced brain injury (RBI) is one of the complications after radiotherapy for head and neck malignant tumors, which seriously affects the quality of life of patients. The pathophysiological mechanism of RBI is not completely clear. Current studies suggest that it is involved in a variety of cells in the central nervous system (CNS), whereas astrocyte, as the largest number of glial cells in the CNS, plays an important role in maintaining the CNS homeostasis and responding to CNS injury. In this article, the role of astrocytes in RBI was reviewed.
ABSTRACT
Objective:To provide insight into the clinical characteristics, therapy and prognosis of patients with radiation-induced brainstem injury after radiotherapy.Methods:From August 2013 to September 2021, 13 patients with radiation-induced brainstem injury were included in this study at Sun Yat-sen Memorial Hospital, and the general information and strategy of radiotherapy were collected. A retrospective analysis was adopted to investigate the clinical and radiological characteristics, treatment and clinical outcomes.Results:There were 13 cases in total, including 4 females and 9 males. The onset age of enrolled patients ranged from 29 to 66 years with an average of (48.15±10.23) years. The median dose targeted at tumor area was 70 Gy with in 33 fractions. The median interval between radiotherapy and the diagnosis of radiation-induced brainstem injury was 24 months. The common clinical manifestations included dysphagia, bucking dysarthria, dizziness and problem with balance. The MRI radiological features were hypointense on T1WI, hyperintense on T2WI, and irregularly enhanced with contrast. The median follow-up was 45 months. Seven cases got improvements, while 3 had no obvious efficacy and 3 cases died. No significant differences in prognosis were observed between those received traditional glucocorticoid and those received bevacizumab treatment( P=0.079). Conclusions:The common symptoms of radiation-induced brainstem injury were symptoms of posterior cranial nerves injury and ataxia. Lesions mostly happened in pons and medulla, with hypointense on T1WI and hyperintense on T2WI. Half of the patients have improved after treatment. There was no significant difference in prognosis between glucocorticoid and bevacizumab treatment.
ABSTRACT
OBJECTIVE: To observe the influence of different courses of electroacupuncture (EA) intervention on recognition memory and the proliferation and differentiation of hippocampal neural stem cells in mice with radiation-induced brain injury, so as to explore its mechanisms underlying improving radiation-induced brain injury. METHODS: Se-venty 30-day old C57BL/6J mice were randomly divided into control, model and EA groups, and the latter two groups were further divided into 1 week (W), 2 W and 3 W subgroups (n=10 in the control group and each subgroup). The ra-diation-induced brain injury model was established by radiating the mouse' left head at a dose of 8 Gy for 10 min by using a radiation linear accelerator. EA (1.5 V, 2 Hz/10 Hz) was applied to "Baihui" (GV20), "Fengfu" (GV14) and bilateral "Shenshu" (BL23) for 30 min, once daily for 1, 2 and 3 weeks, respectively. The learning-cognition memory ability was detected by using novel object recognition test in an open test box to record the time for exploring a novel object (TN) and a familiar object and to calculate the recognition index (RI). The neural stem cells' proliferation and differentiation in the hippocampus tissues were evaluated by counting the number of bromodeoxyuridine (BrdU)-labeled cells, neuronal nuclei (NeuN)/BrdU-positive cells and BrdU/glia fibrillary acidic protein (GFAP)-positive cells under microscope after immunofluorescence stain. RESULTS: After modeling, the TN at 90 min and 24 h and RI of the model subgroup 3 W at 90 min and RI of the model subgroup 1, 2 and 3 W at 24 h were significantly decreased in comparison with those of the control group (P<0.01, P<0.05). Moreover, the number of BrdU-positive cells in the model subgroup 1 W and 2 W, the BrdU/NeuN double-labeled cells in the 3 model subgroups and BrdU/GFAP double-labeled cells in the model subgroup 1 W and 3 W were significantly decreased (P<0.01, P<0.05). Following EA interventions, the TN in the 3 EA subgroups at both 90 min and 24 h, and RI of EA subgroup 3 W at 90 min and EA subgroup 2 W and 3 W at 24 h were considerably increased compared with those of the corresponding 3 model subgroups (P<0.05, P<0.01). The numbers of BrdU-positive cells as well as BrdU/NeuN and BrdU/GFAP double-labeled cells were significantly increased in the 3 EA subgroups (P<0.05, P<0.01, P<0.001). CONCLUSION: EA of GV20, GV14 and BL23 can improve the recognition memory ability of mice with radiation-induced brain injury, which may be related to its effect in promoting the proliferation and differentiation of stem cells in the hippocampus.
ABSTRACT
Objective@#To explore the correlation between microdamage in white matter and radiotherapy dose at early stage after radiotherapy (RT) in patients with nasopharyngeal carcinoma (NPC).@*Methods@#Thirty-three patients who were initially diagnosed with NPC were recruited and received diffusion tensor imaging (DTI) scan and neuro-cognitive scale test within 1 week before RT and the first day after RT. DTI-related characteristic parameters including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ‖), and radial diffusivity (λ⊥) were calculated based on whole-brain voxel analysis method. Paired t-test was conducted to evaluate statistical significance between pre-RT and post-RT groups. In the subgroup analysis, all the subjects were divided into 3 groups according to the average dose of temporal lobe, and each group was set with an equal dose interval range. The DTI-related parameters of whole brain pre-RT and post-RT in each group were statistically compared. All the statistical results were corrected by FDR with a threshold of P<0.05 and clusters>100.@*Results@#FA, MD, λ‖ and λ⊥in the post-RT group significantly differed compared with those in the pre-RT group (P<0.05). The values of FA, MD, λ‖ and λ⊥were 0.455±0.016, (9.893±0.403)×10-4, (13.441±0.412)×10-4 and (8.231±0.429)×10-4, respectively. Subgroup analysis showed that the extent and degree of λ‖ and λ⊥ changes were exacerbated with the increase of the average dose of temporal lobe after RT. Particularly in high-dose group, the average dose range was 25-35 Gy and the extent of regions with significant changes was significantly larger than those in the medium-dose (15-25 Gy) and low-dose groups (5-15 Gy)(P<0.05).@*Conclusions@#DTI can be utilized to detect" normal" brain tissue microdamage in NPC patients at early stage after RT. The average radiation dose of temporal lobe may be one of the reasons for the severity of cerebral microdamage. In the future, DTI technique may be useful for guiding exposure dose of organs at risk during RT planning and to evaluate the cohort with a high risk of cerebral microdamage at early stage after RT, thereby protecting normal cerebral tissues to the maximum extent.
ABSTRACT
Objective To explore the risk factors influencing the outcomes of radiation brain injury after intensity-modulated radiotherapy (IMRT) in patients diagnosed with nasopharyngeal carcinoma.Methods Clinical data of 1 300 nasopharyngeal carcinoma patients treated with IMRT in our hospital during 2006 and 2013 were retrospectively analyzed.Fifty-eight patients presented with radiation brain injury after IMRT.MRI data of these patients during 3-24 months follow-up were collected.The clinical efficacy in the treatment of radiation brain injury was evaluated according to RECIST guidelines.Results Forty-six patients with intact follow-up data were enrolled.The median latency of radiation brain injury was 34 months.Patients were divided into the response (CR+PR) and non-response groups.The risk factors influencing the response rate during 10-12 months and 18-24 months were identified and analyzed.Univariate analysis demonstrated that gender,age,smoking history,T stage,and high-intensity treatment exerted no significant effect upon the objective remission rate during these two time intervals periods.Patients treated with gangliosides obtained high response rate.The response rate was 68.8％ in 10-12 months (P=0.000),and 81.8％ in 18-24 months (P=0.008).Multivariate analysis revealed that use of gangliosides was a favorable factor for mitigating radiation brain injury in two time intervals (OR=19.8 and 13.5;P=0.001 and 0.005).Conclusions Use of gangliosides probably accelerates the healing of radiation brain injury,whereas the clinical efficacy remains to be elucidated by prospective clinical trials.
ABSTRACT
The mechanisms of radiation-induced brain injury ( RBI) remain unclear. Currently a number of studies suggest that inflammatory response may play an important role in RBI. The production of reactive oxygen species, the release of inflammatory mediators, the interactions between neurons, glial cells, and pericytes, and the recruitment of peripheral leukocytes all contribute to the development of radiation-induced brain injury. This article reviews the research progress of the inflammatory response mechanism of radiation-induced brain injury.
ABSTRACT
Objective To analyze the diagnostic value of diffusion tensor imaging (DTI) for early radiation-induced brain injury.Methods We searched CNKI and PubMed and included articles according to the PRISMA statement.FA value, λ||, and λ丄 were pooled, and Forest plot generation, cumulative analysis, sensitivity analysis, and regression analysis were performed.We also used the funnel plot to analyze publication bias.Results A total 11 studies were included for meta-analysis.The results of FA value heterogeneity test were as follows:P=0.000, I2=93.6% in China;P=0.004, I2=82.2% in other countries and regions;P=0.000, I2=91.5% in all regions.The regression analysis of time-dose dependence and study design showed significant and non-significant associations, respectively, with the heterogeneity of these studies (adjusted P=0.026, P=0.005;adjusted P=0.859, P=0.908).The results of λ||and λ丄 heterogeneity tests were as follows:P=0.908, I2=0.0%;P=0.100, I2=56.6%.There was a sign of publication bias by Egger's test (coefficient:-6.26, 95%CI:-9.31 to-3.20, P=0.001) and Begg's test (P=0.004).Conclusions DTI-derived metrics are sensitive and reliable in the diagnosis of early radiation-induced brain injury.
ABSTRACT
Objective To analyze the value of resting state BOLD-fMRI in the early diagnosis of brain injury after nasopharyngeal carcinoma radiotherapy.Methods Four groups of nasopharyngeal carcinoma patients,including before radiotherapy group (G0),0-3 months after radiotherapy group (G1), 3-6 months after radiotherapy group (G2) and 6-9 months after radiotherapy group (G3),were underwent a resting state BOLD-fMRI scan, and Matlab software DPARSF tool was used to analyze and postprocess the data based on G1-G0,G2-G0,G3-G0,G2-G1,G3-G2 and G3-G1.Results Compared with the G0 group,the activity of bilateral hippocampus and temporal lobes was decreased in G1 and G2 groups,and the decreased degree in G2 group was smaller than that in G1 group.Compared with G1 group,brain metabolic activity increased in G2 and G3 group,but did not return to the initial level before radiotherapy.Conclusion Abnormal changes of resting state BOLD-fMRI have an important clinical significance in early diagnosis of radiation-induced brain injury after nasopharyngeal carcinoma radiotherapy.
ABSTRACT
Radiation?induced brain injury is a common adverse reaction to radiotherapy for head and neck carcinoma, and may develop into radiation?induced brain necrosis in some patients. The disease has a substantial impact on the quality of life and 5?year survival in patients. Early diagnosis and prevention are important for the clinical treatment of radiation?induced brain injury. On the other hand, recurrence and pseudoprogression as complications of malignant tumor radiotherapy are also key problems for clinical diagnosis and identification of radiation?induced brain injury. Magnetic resonance imaging ( MRI) , especially functional MRI, provides an important approach for basic and clinical studies of radiation?induced brain injury.
ABSTRACT
Objective To investigate the dynamic changes of the contents of brain water and Ca,Fe,Cu,Zn,Mg and microvascular damage in hippocampal tissue of radiation-injured rat brain.Methods The rats were randomly divided into control group,protective group (with intraperitoneal injection of 10％ MgSO4,400 mg/kg body weight + a single dose of 20 Gy electron beam irradiation in whole brain) and irradiation alone group (with intraperitoneal injection of normal saline,400 mg/kg body weight + a single dose of 20 Gy electron beam irradiation to the entire brain) with 18 rats assigned to each group and 3 rats sampled at each time point.Radiation-induced brain injury (RBI) was modeled by irradiating the rat' s whole brain with 5 MeV electrons.A dry-wet weight method was used to detect brain water content (BWC),and the level of microvascular damage was detected with HE staining of brain tissue slices,and the contents of Ca,Fe,Cu,Zn,Mg in hippocampus were detected with inductively coupled plasma atomic emission spectroscopy at different time points after radiation.Results BWC in the irradiated rats at 7,14 and 30 d post-irradiation was higher than that of control group (t =3.21,-2.11,2.82,P ＜0.05),andBWC in the protective group was less than that in the irradiated group (t =2.84,4.33,1.90,P ＜ 0.05).Microvascular thrombosis was induced in the radiated brain but this thrombosis was reduced by MgSO4.Thecontents of Ca and Fe in the brain tissue after 1,3,7 d of irradiation was higher than that of control group(t =11.41,6.81,14.03,17.17,6.89,9.12 and 5.43,5.66,3.60,P ＜ 0.05),and the content of Cain the protective group at various time post-irradiation was less than that in the irradiated group (t =5.35,5.28,11.02,14.26,5.68,9.10,P ＜0.05).The content of Cu (1,7,14,60 d post-irradiation) andZn (1,7,14,30,60 d post-irradiation) of the irradiated group was less than that of the control group(t =4.24,3.76,4.76,3.86 and 5.25,4.78,26.53,6.67,11.37,P ＜ 0.05),and the content of Cuin the protective group at different time points post-irradiation was less than that of the irradiated alonegroup (t =4.23,3.57,4.01,4.73,3.78,3.44,P ＜0.05),the content of Zn in the protective group(14 d post-irradiation) was higher than that of the irradiated group (t =6.21,P ＜ 0.05).The content ofMg in the irradiated group (7 d post-irradiation) was less than that of the control group (t =5.85,P ＜0.05).Conclusions The contents of Ca,Fe,Cu and Zn were imbalanced in the radiation-injured ratbrain,and the supplement of MgSO4could recover the balance of Ca,Fe,Cu and Zn content and alleviateradiation-induced brain injury.
ABSTRACT
Objective To explore the dynamic changes of endothelial barrier antigen (EBA) and vascular endothelial growth factor (VEGF) expressions in cerebral cortex under the condition of blood-brain barrier damage in rats following radi?ation-induced brain injury, which provided clinical references. Methods Forty-eight clean grade male SD rats were divid?ed into the control group and 7 d, 14 d, 28 d after brain irradiation group (n=12 for each group) by using stochastic indicator method. The radiation-induced brain injury model was established by using electronic computer X-ray tomography tech?nique. The 3%Evans blue (EB) was injected into rats according to the dose of 3 mL/kg via the tail vein, then the blood ves?sels of cerebral cortex were exposed after having a craniotomy. EB extravasation was detected by microcirculation micro?scope. The permeability of blood-brain barrier was evaluated by using microscope vascular camera device. The expressions of EBA and VEGF in the cerebral cortex were measured by immunohistochemistry staining in each group. Results Both of EB extravasation and VEGF expression in rat cerebral cortex were significantly increased in injury group at day 7, 14 and 28 after brain irradiation compared with those of control group (P<0.05), and which were gradually decreased from day 7 to day 28 after brain irradiation. There were significant differences in EB extravasation and VEGF expression between the injury subgroups (P<0.05). There was a positive correlation between EB extravasation and VEGF expression (r=0.898, P<0.001). The expression levels of EBA were decreased at different time points in injury groups compared with those of control group (P<0.05), and gradually increased from day 7 to 28 after injury. There were significant differences in expression levels of EBA between injury subgroups (P<0.05). The expression of EBA was negatively correlated with EB extravasation (r=-0.866, P<0.001). Conclusion The increases of blood-brain barrier permeability have important relation to the decreases of EBA expression and the increases of VEGF expression after radiation-induced brain injury.
ABSTRACT
Objective To investigate the dynamic changes of nuclear factor-κB(NF-κB) during brain injury of irradiated rats.Methods According to the random number table method,82 healthy Sprague-Dawley rats were divided into two groups:50 rats in the irradiation group and the other 32 rats in the control group given sham-irradiation.The whole brains of rats in the irradiation group were irradiated with a single dose of 20 Gy electron beam to establish an animal model of radiation-induced brain injury.All brain tissues were respectively taken out 1,3,7,14 and 28 d after irradiation.The quantificational real-time-polymerase chain reaction (QRT-PCR) was used to detect the expressions of the NF-κB mRNA while the expression of NF-κB protein was analyzed by ELISA and Western blot.The positioning expression of NF-κB protein in the hippocampus was measured with immunohistochemical staining.Results In the irradiation group,the expression of NF-κB mRNA significantly increased at 3 and 7 d following irradiation (t =37.79,35.30,P ＜ 0.05) and it approached a peak value on the third day following irradiation.The expression of NF-κB protein in whole brain tissues after irradiation was up-regulated and reached a peak on the first day post-irradiation and it was significantly higher than controls at 1,3,7,14 d after irradiation (t =30.94,14.87,27.17,13.27,P ＜ 0.05) then declined and dropped to the normal level by 28 d.The results of immunohistochemical staining showed that the number of NF-κB positive cells in the hippocampus increased at 1,3 and 7 d following irradiation (t =-8.49,-4.47,-3.46,P ＜ 0.05).Conclusions After irradiation,the expressions of NF-κB mRNA and corresponding protein first increase and then later decrease,which promotes the development of brain injury.
ABSTRACT
Objective To investigate the dynamic changes of VEGF mRNA and protein in the injured brain of rats irradiated by 20 Gy of electron beams.Methods A total of 114 Sprague-Dawley rats were randomly divided into two groups,42 rats in sham group with sham-irradiation,and the other 72 rats in irradiation group that the whole brains of rats were administered with a single dose of 20 Gy electron beam (6 MeV) to establish an animal model of radiation-induced brain injury.All rats were terminated at 1,3,7,14,28,42,56 d post-irradiation respectively.The pathological changes were observed with light microscopies.Real-time quantitative reverse transcriptase-PCR was used to measure the level of VEGF mRNA in the brain tissue.The expression of VEGF protein in whole brain tissue was detected with Western blot.The VEGF protein expression in brain endothelium,gliacyte and neuron were measured via immunohistoehemistry with computerized image processing.Results The pathological process of radiationinduced brain injury (RBI) included brain endothelial cell damage,brain edema,thrombosis formation and ablation,revascularization and angiogenesis.In the irradiation group,the expression of VEGF mRNA was declined significantly at 1,3,7,2g,42 d post-irradiation (t =16.275-46.118,P ＜ 0.05).The VEGF protein expression in whole brain tissue was up-regulated at 1 and 7 d after irradiation,but downregulated at 3,14,28,42,56 d post-irradiation.There were VEGF positive cells in the brain endothelium,gliacyte and neuron at 1 d after irradiation.The expression of VEGF protein in gliacyte and neuron significantly was increased at 1,14,42,56 d post-irradiation (t =-8.394--4.697,P ＜ 0.05),and increased significantly in brain endothelial cells at 1,14,and 42 d after irradiation (t =-5.554--4.159,P ＜ 0.05).Conclusions The expression of VEGF mRNA was relatively suppressed in RBI rats.The expression of VEGF protein in whole brain tissue was up-regulated only at the early stage of RBI.The expressions of VEGF protein in brain endothelium,gliacyte and neuron were increased in the observation period,which induced brain edema and the formation of thrombosis at the acute RBI stage,and participated in the progression of angiogenesis and thrombosis ablation at the early-delayed RBI stage.
ABSTRACT
Objective To explore the sensibility of radiation-induced normal brain injury in different regions at acute stage after all cranial radiotherapy by MR diffusion tensor imaging (DTI).Methods A total of 44 patients with brain tumors undergoing whole cranial radiotherapy were examined with convention and enhancement magnetic resonance imaging and diffusion tensor imaging before and three weeks after radiotherapy.The apparent diffusion coefficient ( ADC ),fractional anisotropy ( FA),relative anisotropy (RA) and volume ratio(VR) of DTI in contralateral brain hemisphere after radiotherapy with the dose of 27 Gy were measured and analyzed in different regions.Results No abnormal signal intensities were revealed in convention and enhancement MRI.ADC values in superficial cerebral convolution gray matter,ADC and VR values in deep gray nucleus were increased(t =- 3.321,- 2.810,P ＜ 0.05 ),while FA and RA values in deep gray nucleus were descended( t =2.906,2.349,P ＜0.05 ).There was no statistically significant difference among DTI index in other regions.Conclusions The brain gray matter more sensitive to radiation-induced brain injury in than white matter at acute stage of radiation.DTI could be used to evaluate the functional changes at the histocytology level of radiation-induced brain injury,and to explain the early clinical reactions after radiotherapy.
ABSTRACT
Objective To study the diagnosis and treatment of delayed radiation-induced brain injury. Methods 21 patients with delayed radiation-induced brain injury were diagnosed by CT, MRI and MRS, and were treated with dehydration, corticosteroid, neuroprective drugs and hyperbaric oxygen or surgery. Results The symptoms of 66.7% patients were obviously improved, 19.0% patients partly recovered and the symptoms of 14.3% patients were not obviously improved. Conclusion The early diagnosis and reasonable treatment could decrease delayed radiation-induced brain injury to minimal extent. The operative treatment should be performed in the patients who had operative indicators. And it was important to prevent the occurrence of delayed radiation-induced brain injury.