Nat Med: The first Phase III trial found that metformin improved working and statement memory in children with brain tumors who received radiotherapy.

!---- Today, our old friend, metformin, is here again! It comes with the potential to repair the brain and restore cognitive ability! In the journal Nature Medicine, researchers at the Institute of Medical Sciences at the University of Toronto and The Children's Hospital of Toronto published their Phase III double-blind placebo-controlled trial.for brain tumors in children who received cranial radiotherapy, metformin significantly improved their working memory and statement memory function, repairing white matter damage, compared to placebos.mammalian brains have resident neuroprecursor cells that play an important role in neurodevelopment and are potential candidates for the repair of nerve damage in the brain.induced the proliferation and differentiation of endogenous neuroprecursor cells (NPC) in mice, which can promote neural repair in the mouse brain, but this pathway has not been proven in humans.metformin was previously found to promote neurogenesis by activating the atypical protein kinase C (aPKC)-CREB binding protein pathway in NPC, and in newborn mice with brain injury, metformin also promoted NPC activation, neurogenesis and the increase of protrusion glial cells, improving motor system and cognitive function.this time, the researchers were also the first to test the mice, where they gave the adolescent mice (17 days after birth) head radiation therapy, and 1-2 days after treatment, the neural stem cells of the lower ventricles (SVZ) and hippocampus reflux (DG) were reduced by 53% and 75%, respectively, and after 5 weeks, the neural stem cells of SVZ basically returned to their initial levels, but the DG region was still reduced by 44%.But if the mice starttaking taking metformin one day after radiotherapy, they have been taking it for 25 days, and the neural stem cell levels in the DG region of the mice have been fully restored! For mature neurons, the recovery of metformin only worked significantly in female mice.researchers also found that radiotherapy had different effects on brain function in female and male mice, and after radiotherapy, female mice performed poorly in the Y-maze experiment, indicating impaired working memory, while male mice performed poorly in new location recognition experiments, indicating impaired spatial memory. Aftermetformin treatment, the working memory ability of the female mice was restored, but the spatial memory ability of the male mice was not.the results of the blank control group, radiotherapy group and radiotherapy-metformin group in the Y maze of female mice (o) and male mice (p), but the effects of the test in the female mice supported the researchers in a clinical trial, a cross-test involving 24 children who had received cranial brain radiotherapy.patients were divided into 2 groups, one group of metformin and then placebo, the other group of placebo and metformin, treated for 12 weeks, and 10 weeks of elutation when the treatment was exchanged.the trial process did not have serious adverse events associated with metformin during treatment, the most common adverse events included vomiting, diarrhea, headache fatigue and nausea, with an average of 2.5 adverse events per patient during treatment and 1.6 in placeofocases during treatment.researchers analyzed the recovery of the three cognitive functions of impaired working memory, statement memory and information processing speed in patients using different tests, and showed that metformin was significantly better than placebo, especially working memory and statement memory, and that the recovery of cognitive function was better than in patients with first placebo and then metformin.this may be due to the fact that some of the patients themselves have more severe acute brain injury due to the effects of tumors and surgery, and these patients were assigned more treatment for metformin during the first 12 weeks of treatment.researchers also scanned the brains of patients, focusing on the blood flow of the luteum and the hippocampus.the carcass is connected with NPC in the lower ventricle, and also contains protrusion cells with less protrusion cells, and the scan results show that the axonwater content (AWF) is higher than that of patients treated with pentobarbital and metformin, and AWF is a sensitivity indicator of white matter damage, which increases to show that metformin causes the damage of the carcass to be repaired.in mouse experiments, researchers observed the occurrence of new neurons in the DG region, and in patients, they tested changes in the blood flow of the hippocampus after treatment, because cell proliferation and angiogenesis were associated with increased blood flow in the hippocampus, which reflected neurogenesis. but neither the left hippocampus nor the right hippocampus observed significant differences in blood flow. combined with the results of clinical trials and animal trials, the researchers believe that metformin treatment is tolerable and safe for post-treatment childhood brain tumor patients, but also initially showed a recovery of cognitive function, which is found to take metformin type 2 diabetes patients with low incidence of dementia, audio-visual memory is stronger. in the future, more patients are needed, followed-up phase III clinical trials for longer periods of time to validate this results. .