Project description:We report the application of single cell sequencing technology for high-throughput profiling in mice brain cells.In order to search for SCZ-related molecular pathways in different brain cell types affected by immune activation, we first activated the peripheral immune system by intraperitoneal injection (IPI) of lipopolysaccharide (LPS) into adolescent mice twice on post-natal day 45 and 46, and collected the serum from the mice on the third day. Then we performed intracerebroventricular injection (ICVI) of 15 ul of serum from the immune-activated mice. After ICVI of immune-activated serum for one week, we carried out single-cell transcriptome sequencing on the brains from the mice. This study provides characterization of diverse cell populations towards different treatments.
Project description:Stereotactic radiosurgery (SRS) has been shown to be efficacious for treatment of limited brain metastasis (BM), however, the effects of SRS on human brain metastases have yet to be studied. We performed genomic analysis of resected brain metastases from patients whose resected lesion was previously treated with SRS. Our analyses demonstrated for the first time that patients possess a distinct genomic signature based on type of treatment failure including local failure, leptomeningeal spread, and radio-necrosis. Examination of the center and peripheral edge of the tumors treated with SRS indicated differential DNA damage distribution and an enrichment for tumor suppressor mutations and DNA damage repair pathways along the peripheral edge. Furthermore, the two clinical modalities used to deliver SRS, LINAC and GK, demonstrated differential effects on the tumor landscape even between controlled primary sites. Our study provides, in humans, biological evidence of differential effects of SRS across BM’s.
Project description:The purpose of this study is to determine whether AGuIX (Activation and Guidance of Irradiation by X-ray) gadolinium-based nanoparticles make radiation work more effectively in the treatment of patients with brain metastases that are more difficult to control with stereotactic radiation alone.
Project description:Stereotactic radiosurgery (SRS) has been shown to be efficacious for treatment of limited brain metastasis (BM), however, the effects of SRS on human brain metastases have yet to be studied. We performed genomic analysis of resected brain metastases from patients whose resected lesion was previously treated with SRS. Our analyses demonstrated for the first time that patients possess a distinct genomic signature based on type of treatment failure including local failure, leptomeningeal spread, and radio-necrosis. Examination of the center and peripheral edge of the tumors treated with SRS indicated differential DNA damage distribution and an enrichment for tumor suppressor mutations and DNA damage repair pathways along the peripheral edge. Furthermore, the two clinical modalities used to deliver SRS, LINAC and GK, demonstrated differential effects on the tumor landscape even between controlled primary sites. Our study provides, in humans, biological evidence of differential effects of SRS across BM’s.
Project description:The aim of the experiment was to identify differences in gene expression in the whole brain hemisphere due to the presence of a brain tumor. At 21 days after a stereotactic injection of 5 x 10E4 rat C6 glioma cells into the right striatum of the rat the animals were sacrificed and the tumor-bearing brain hemispheres were isolated. The control animals were left untreated. The focus of the experiment was on the changes in gene expression due to the immune cells infiltrating the tumor and the surrounding brain parenchyma.
Project description:The aim of the experiment was to identify differences in gene expression in the microglia due to the presence of a brain tumor, at 14 days after a stereotactic injection of 5 x 10E4 rat C6 glioma cells into the right striatum of the rat. The control (naive) animals were left untreated. The brain hemispheres from the control animals, or the tumor-bearing hemispheres were dissected, gently dissociated into cells and the microglia (CD11b+CD45low cells) were sorted out.
Project description:Mice (n=85) were anaesthetised by ip injection (0.1 ml/10 g) of xylazine (5%) and ketamine (10%) diluted in sterile water. After placing animals in a stereotactic frame, the skull surface was exposed and holes were drilled at the appropriate sites to allow bilateral infusion of ibotenic acid (10 ï¾µg/ï¾µl in saline) with a glass capillary (40 ï¾µm external tip) glued to a 1 ï¾µl Hamilton syringe connected to stereotactic syringe pump (KDS 310, KD scientific). Antero-posterior (AP), lateral (L) and vertical (V) coordinates (in mm) for micro-infusions in the dorsal hippocampus, were taken relative to the bregma: (1) AP -1.7, L +/- 1, V -1.5; (2) (2) AP -2.2, L +/- 1.5, V -1.5; (3) AP -2.6, L+/- 2, V -1.5 (based on brain atlas by Paxinos and Franklin, 2004). The infused volume of ibotenic acid or PBS was 30 nl per injection site. The rate of infusion was 30 nl/min and the needle was left in situ for another 2 min, before being slowly retracted.
Project description:MgSO4 is given to prevent preterms neurological deficits. We have investigated proper effects and hypoxia-ischemia interfering effects of MgSO4 on transcription in neonate mice at day 5 (a brain development stage mimicking preterm maturity), at neuroprotection dose (600 mg/kg). Pools of RNA from 6 forebrains (3 males and 3 females) were used for total RNA extraction at 5 times post single MgSO4 injection (1.5H, 3H, 6H, 12H, 24H). Separately, MgSO4 effects were assessed post hypoxia-ischemia (3H and 12H). Co-hybridization of MgSO4-treated mRNA (labelled Cy5) and control tissues mRNA (labelled Cy3) were performed on Agilent (design 026655) micro-arrays in 4-7 replicates. Co-hybridization of saline injected (Labelled Cy3) or MgSO4 injected (Labelled Cy5) hypoxia-ischemia (according to Rice Vannucci (RV) procedure) exposed mice brains were performed on Aglient (design 026655) microarrays in triplicates.