To study the protective effect of Huangqi Baihe Granules on Radiation brain injury based on network pharmacology and experiment.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqi baihe Granules (HQBHG), which is a key Chinese medical prescription, has a remarkable efficacy in oxidative stress and inflammation. Nevertheless, the therapeutic effect on Radiation brain injury (RBI) has rarely been studied. AIM OF THE STUDY: The study aimed to verify the effect of HQBHG against RBI and explore its potential mechanism. METHODS: The potential targets and mechanisms of HQBHG against RBI were predicted by network pharmacology and verified by established rat model of RBI Firstly, the therapeutic effect of HQBHG in RBI was confirmed by water maze test, HE staining and Enzyme-linked immunosorbent assay (ELISA). Secondly, the potential critical anti-RBI pathway of HQBHG was further explored by water maze, HE staining, immunofluorescence assays, ELISA and western blot. RESULTS: A total of 43 HQBHG anti-RBI targets were obtained. Gene Ontology (Go) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotations showed that the treatment of HQBHG in RBI might be mainly related to oxidative stress, inflammation and PI3K/AKT pathway. Experimental studies have indicated that HQBHG can improve spatial learning and memory ability, alleviate pathological damage of brain tissue in RBI of rats. HQBHG also can down-regulate the levels of IL-1ß, TNF-α, ROS and MDA, meanwhile, GSH was significantly up-regulated. In addition, the HQBHG can increase the protein expression phosphorylations PI3K (p-PI3K), phosphorylations AKT(p-AKT) and Nrf2 in the brain tissue of RBI. CONCLUSION: HQBHG may alleviated RBI by regulated oxidative stress and inflammatory response through PI3K/AKT/Nrf2 pathway.

Bibliometric and visualization analysis of radiation brain injury from 2003 to 2023.

Background: Over the past two decades, the field of radiation brain injury has attracted the attention of an increasing number of brain scientists, particularly in the areas of molecular pathology and therapeutic approaches. Characterizing global collaboration networks and mapping development trends over the past 20 years is essential. Objective: The aim of this paper is to examine significant issues and future directions while shedding light on collaboration and research status in the field of radiation brain injury. Methods: Bibliometric studies were performed using CiteSpaceR-bibliometrix and VOSviewer software on papers regarding radiation brain injury that were published before November 2023 in the Web of Science Core Collection. Results: In the final analysis, we found 4,913 records written in 1,219 publications by 21,529 authors from 5,007 institutions in 75 countries. There was a noticeable increase in publications in 2014 and 2021. The majority of records listed were produced by China, the United States, and other high-income countries. The largest nodes in each cluster of the collaboration network were Sun Yat-sen University, University of California-San Francisco, and the University of Toronto. Galldiks N, Barnett GH, Langen KJ and Kim JH are known to be core authors in the field. The top 3 keywords in that time frame are radiation, radiation necrosis, and radiation-therapy. Conclusions: The objective and thorough bibliometric analysis also identifies current research hotspots and potential future paths, providing a retrospective perspective on RBI and offering useful advice to researchers choosing research topics. Future development directions include the integration of multi-omics methodologies and novel imaging techniques to improve RBI's diagnostic effectiveness and the search for new therapeutic targets.

Exposure to X-rays Causes Depression-like Behaviors in Mice via HMGB1-mediated Pyroptosis.

The widespread application of ionizing radiation in industrial and medical fields leads to the increased brain exposure to X-rays. Radiation brain injury (RBI) seriously affects health of patients by causing cognitive dysfunction and neuroinflammation. However, the link between X-ray exposure and depressive symptoms and their detailed underlying mechanisms have not been well studied. Herein, we investigated the potential depression-like behaviors in mice exposed to X-rays and then explored the role of HMGB1 in this injury. We found that X-ray stimulation induced the generation of reactive oxygen species (ROS) in the prefrontal cortex in a dose-dependent manner, leading to the occurrence of depression-like behaviors of the mice. Moreover, X-ray exposure increased the expression of HMGB1, activated NLRP3 inflammasome signaling pathway and microglial cells, and then facilitated the release of pro-inflammatory cytokines, resulting in the pyroptosis and neuron loss both in vivo and in vitro. Additionally, glycyrrhizin (Gly), which is a HMGB1 inhibitor, reversed X-ray-induced behavioral changes and neuronal damage. Our findings indicated that HMGB1-mediated pyroptosis was involved in radiation-induced depression.

Systematic review and meta-analysis of arterial spin-labeling imaging to distinguish between glioma recurrence and post-treatment radiation effect.

BACKGROUND: At present, the use of arterial spin-labeling (ASL) imaging to assess the recurrence of gliomas and post-treatment radiation effect (PTRE) is limited, and the results of studies on ASL are quite different. To date, no multi-center, large-scale studies have been conducted to confirm its diagnostic efficacy. This study sought to systematically evaluate the diagnostic value of ASL imaging in distinguishing between glioma recurrence and PTRE. METHODS: Databases, including Medline, Cochrane Library, Pub Med, Web of Science, Embase, China National Knowledge Infrastructure, Wan Fang, were searched to retrieve studies that used ASL imaging to diagnose glioma recurrence and radiation-induced brain injury. The search deadline was August 31, 2021. Two reviewers independently screened the literature according to set literature inclusion and exclusion criteria, extracted basic data from the literature, and evaluated the quality of the literature. Revman 5.3 software was used to analyze the included research data. RESULTS: Ten studies, comprising 216 patients with glioma recurrence and 152 patients with PTRE, were included in the meta-analysis. The results showed that cerebral blood flow [mean difference (MD) =1.67, 95% confidence interval (CI): 0.89-2.46, P=0.000], relative cerebral blood flow (MD =1.20, 95% CI: 0.91-1.49, P=0.000), and relative cerebral blood volume (MD =1.29, 95% CI: 0.98-1.59, P=0.000); this 3 indicators between glioma recurrence and PTRE were significantly different. DISCUSSION: ASL imaging has high diagnostic value in distinguishing between glioma recurrence and PTRE.

CORM-3 Regulates Microglia Activity, Prevents Neuronal Injury, and Improves Memory Function During Radiation-induced Brain Injury.

OBJECTIVE: This study aims to explore in detail, the mechanism of the carbon monoxide releasing molecule-3 (CORM-3) in regulating the activity of microglia (MG) in the treatment of radiation brain injury (RBI). METHODS: The brain injury models of BV2 cells and Balb/C mice were established and randomly divided into three groups: the normal control group (CON), the single radiation group (RAD), and the radiation plus CORM-3 intervention group (RAD+CORM). Immunofluorescence was used to observe the effects on activation of the MG. The expressions of inflammatory factors, such as intercellular adhesion molecule-1 (ICAM-1) and inducible nitric oxide synthase (iNOS), were detected by Western blot. Neuron apoptosis and regeneration in the radiation brain injury (RBI) model were detected by neuronal nuclear antigen (NeuN)+TUNEL and NeuN+BrdU double staining. A Morris water maze was used to assess the spatial learning and memory of the mice. RESULTS: Within 48 h after radiation, CORM-3 inhibited activation of the MG, blocked the phosphorylation of P38, and increased the expression of ICAM-1 and iNOS. Therefore, CORM-3 might alleviate MG-mediated neuronal apoptosis and promote neural regeneration in the subgranular zone (SGZ) of the dentate gyrus of the hippocampus. CORM-3 could increase the swimming distance and platform-stay time of the mice in the target platform quadrant after radiation. CONCLUSION: CORM-3 could effectively improve the inflammatory response induced by activation of the MG, reduce neuronal apoptosis, promote neural regeneration, and improve the learning and memory performance of mice after radiation.

Neuroprotective Effects of Umbilical Cord-Derived Mesenchymal Stem Cells on Radiation-Induced Brain Injury in Mice.

OBJECTIVE: To investigate the neuroprotective effects of umbilical cord-derived mesenchymal stem cells (UC-MSCs) on radiation-induced brain injury (RIBI). METHODS: Thirty female C57BL/6 mice were randomly divided into three groups: control (CON), whole brain irradiation (WBI), and the cell therapy (MSC) group. Mice in the WBI and MSC groups received a single, whole brain irradiation treatment with 15 Gy of 60Co. Learning and memory were evaluated in the mice using the step-down avoidance test. The neuronal changes in the hippocampal cornu ammonis (CA) 1 region were observed using hematoxylin eosin (H&E) staining. The changes in astrocytes were visualized with glial fibrillary acidic protein immunohistochemistry, and the expression of TNF-α, IL-6, and IL-10 was detected by quantitative polymerase chain reaction (qPCR) along with Enzyme linked immunosorbent assay (ELISA). RESULTS: Compared with mice in the WBI group, learning and memory in the MSC mice were significantly increased (P<0.05), neuronal degeneration and necrosis were significantly decreased (P<0.05), and the number of astrocytes was significantly increased (P<0.05). The levels of the in˙ammatory cytokines, TNF-α and IL-6, were significantly decreased (P<0.05), however, the inhibitory factor IL-10 was significantly increased (P<0.05). CONCLUSIONS: UC-MSCs play a neuroprotective role by inhibiting brain cell injury and neuroinflammation.

Grafted Neural Stem Cells Show Lesion-Specific Migration in Radiation-Injured Rat Brains.

Neural stem cells (NSCs) exhibit preferential homing toward some types of brain lesion, but their migratory property during radiation brain injury (RBI) remains unexplored. Here, we use the superparamagnetic iron oxide (SPIO)-labeled magnetic resonance imaging (MRI) technology to determine the migration of transplanted NSCs in two partial RBI models in real time, created by administering 30-55 Gy of radiation to the right or posterior half of the adult rat brain. SPIO-labeled NSCs were stereotactically grafted into the uninjured side one week after RBI. The migration of SPIO-labeled NSCs in live radiation-injured brains was traced by MRI for up to 28 days after engraftment and quantified for their moving distances and speeds. A high labeling efficiency (>90%) was achieved by incubating NSCs with 100µg/ml of SPIO for 12-24 hours. Upon stereotactic transplantation into the healthy side of the brain, SPIO-labeled NSCs were distinctively detected as hypointense signals on T2-weighted images (T2WI), showed sustained survival for up to 4 weeks, and exhibited directional migration to the radiation-injured side of the brain with a speed of 86-127 µm/day. The moving kinetics of grafted NSCs displayed no difference in brains receiving a high (55 Gy) vs. moderate (45 Gy) dose of radiation, but was slower in the right RBI model than in the posterior RBI model. This study shows that NSCs can be effectively labeled by SPIO and traced in vivo by MRI, and that grafted NSCs exhibit directional migration toward RBI sites in a route-dependent but radiation dose-independent manner.

Beneficial effects of Angiotensin II receptor blockers in brain disorders.

A canonical brain Renin-Angiotensin System (RAS), like the canonical peripheral RAS, has long been proposed as a major regulator of brain function. Because of methodological limitations, however, this system is in urgent need of critical revision. The Angiotensin II AT1 receptors have been confirmed as key factors in the regulation of brain function, and AT1 receptor over activity has been established as a major and early injury factor in the development of many brain diseases. Consequently, Angiotensin Receptor Blockers (ARBs), compounds widely used to treat cardiovascular and metabolic disorders, are excellent candidates for repurposing for the treatment of brain disorders. This review will discuss some of the reasons why revisiting brain RAS is a pressing necessity, will present evidence for a participation of AT1 receptor over activity in the development of major brain disorders, and will present definite evidence of ARBs neuroprotective effects. The review will focus on the beneficial effects of ARB therapy in stroke, neurodegenerative disorders including Alzheimer's and Parkinson's diseases, traumatic brain injury, radiation- induced brain damage, stress and mood disorders.

Heavy ion and X-ray irradiation alter the cytoskeleton and cytomechanics of cortical neurons.

Heavy ion beams with high linear energy transfer exhibit more beneficial physical and biological performance than conventional X-rays, thus improving the potential of this type of radiotherapy in the treatment of cancer. However, these two radiotherapy modalities both cause inevitable brain injury. The objective of this study was to evaluate the effects of heavy ion and X-ray irradiation on the cytoskeleton and cytomechanical properties of rat cortical neurons, as well as to determine the potential mechanism of neuronal injury after irradiation. Cortical neurons from 30 new-born mice were irradiated with heavy ion beams at a single dose of 2 Gy and X-rays at a single dose of 4 Gy; subsequent evaluation of their effects were carried out at 24 hours after irradiation. An immunofluorescence assay showed that after irradiation with both the heavy ion beam and X-rays, the number of primary neurons was significantly decreased, and there was evidence of apoptosis. Radiation-induced neuronal injury was more apparent after X-irradiation. Under atomic force microscopy, the neuronal membrane appeared rough and neuronal rigidity had increased. These cell changes were more apparent following exposure to X-rays. Our findings indicated that damage caused by heavy ion and X-ray irradiation resulted in the structural distortion and rearrangement of the cytoskeleton, and affected the cytomechanical properties of the cortical neurons. Moreover, this radiation injury to normal neurons was much severer after irradiation with X-rays than after heavy ion beam irradiation.

Experimental study of Gadofluorine M enhancement in early diagnosis of radiation brain injury by MRI in rats / 中华放射医学与防护杂志

Objective To explore the value of Gadofluorine M,a novel M RI enhancement agent,in the diagnosis the early radiation brain injury.Methods Seventy-two Wistar rats were randomly divided into 5 equal groups.To establish the radiation injury model,the rat's posterior brain was irradiated with 0(blank controls),25,35,45,55,and 65 Gy,respectively.After irradiation MR plain scanning and Gadofluorine M enhancement scanning (after the T1WI and T2WI scanning Gf at the dosage of 0.1 mmol/kg was injected intravenously and scanning was performed again 12 h later) were performed once a week for 8 weeks.Another 12 rats were randomly divided into 2 equal groups to exposure to 55 and 65Gy,respectively,and MR scanning was performed once a week for 8 weeks since the third week after MR.After T1WI and T2WI scanning Gd-DTPA was injected intravenously,MR was conducted again 30 min later,and Gf was injected intravenously (Gd-DTPAenhancement and Gf enhancement contrast).The MR image and the pixel count were compared.Since the third week 2 rats from the Gf enhancement scanning group and 1 rat from the Gd-DTPA enhancement and Gf enhancement contrast were killed after MR with their brains taken out to undergo pathological examination.Results No abnormal signal changes were found in MRI in 25 and 35 Gy groups within 2 months after irradiation.A high signal in the Gf enhancement T1 WI image was found in 45,55,and 65 Gy groups within the period of 4-6 weeks after radiation.The signal intensity was significantly higher than that of the control,25,and 35 Gy groups(F =2.15,P <0.05).The emerge time of this signal was negatively correlated with the dose of radiation(r =-0.62,P < 0.05).When there was no obvious change was found by Gd-DTPA enhancement,a high signal representing change of injury could be found in Gf enhancement in the same rat.The signal intensity was significantly enhanced in Gf enhancement compared to the Gd-DTPA enhancement (F = 2.74,P <0.01).Histopathology examination of the 65 Gy group showed frosted degeneration in part of the region,however,no obvious necrotic damage was found in other groups.Conclusions The Gf enhancement change appears before histopathological changes,it helps discover early radiation injury in brain.Compared to the regular MRI and Gd-DTPA enhancement,Gadofluorine M enhancement has obvious advantage and is worth further research and application.

Single-fraction High-dose Brain Irradiation:Experimental MR Spectroscopy and Metabolism Study in Vivo / 实用放射学杂志

Objective To analyse the ultrastructural and metabolic changes of brain injury after single-fraction high-dose radiation in rabbits by means of proton 1-hydrogen) magnetic resonance spectroscopy ~1H MRS) ,in order to provide the basic theory for early detection of radiation-induced brain injury.Methods Experimental model of single-fraction high-dose radiation-injured brain was established in 40 rabbits , which were randomly divided into 4 groups and underwent 10, 15, 20 Gy and 30 Gy radiation , respectively. Proton MRS in a clinical MR imager was used to ascertain the amount of whole-brain N-acetylaspartic acid NAA), lactic acid Lac), choline Cho), creatine Cr) before and within 8 weeks after focused single-fraction high-dose irradiation therapy. Metabolic maps of NAA, Lac, Cho and Cr were created from MRS data set. Detection of irradiation injury among the tested models was assessed by receiver operating characteristic analysis and by quantitative signal intensity changes. The peak values of NAA , Lac , Cho and Cr on MRS before and after radiation were measured. Histopathology and electron microscope were used to ascertain changes of the ultrastructural organization in the irradiated area.the results were compared and statisti-cally analyzed. Results Initially MRS was found a slightly decrease. Until obviously change was detected, statistical significance variation of MRS occurred. A significant decrease in~1H MRS occurred at the early stage of brain injury induced by single-fraction high-dose irradiation.Conclusion ~1H MRS may be regarded as a noninvasive and sensitive means for the detection of early radiation-induced brain injury.

Early Radiation-Induced Temporal Lobe Injury after Radiotherapy for Nasopharyngeal Carcinoma:Features of MR DTI / 实用放射学杂志

Objective To evaluate the diagnostic values of diffusion tensor imaging(DTI)in early radiation-induced brain injury of the temporal lobes.Methods Conventional and MR diffusion tensor imaging examinations were performed in 23 patients following radiotherapy for nasopharyngeal carcinoma(NPC)and in 28 age-matched healthy controls.Isotropic apparent diffusion coefficient(ADCiso)and anisotropic index were measured in the white matter on both of the temporal lobes.Results The value of ADCiso,fractional anisotropy(FA),relative anisotropy(RA)and 1 minus volume ratio(1-VR)were(644.08?56.80)?10-6 mm2/s,0.394?0.074,0.344?0.075 and 0.182?0.072 respectively.In comparison with control group,these values were significant decreased(P