Hypoxia-Induced Glioma-Derived Exosomal miRNA-199a-3p Promotes Ischemic Injury of Peritumoral Neurons by Inhibiting the mTOR Pathway

Figure 1

The peritumoral hypoxic area overlapped with the cytotoxic edema region. (a) An anaplasia astrocyte glioma (WHO III) sample showed a hyperintense signal in T1 contrast scanning (red arrow), and peritumoral edema, which indicated potential hypoxia, was detected in T2 and Flair scanning images (yellow arrow). (b) When the patient received 18-FDG PET/CT scanning, hypoxia was found in the tumor region (blue ring) and peritumor edema region (yellow arrow). Moreover, when using 18F-FMISO, hypoxia (blue area) shared the same region as T2 and Flair scanning, which further indicated that peritumoral edema was closely correlated with the occurrence of hypoxia around the tumor. (c) In another anaplasia astrocyte glioma (WHO III) patient, T1+contrast, Flair, and MR PW studies revealed that regions of edema featured low perfusion characteristics (c). The analyzed sample was obtained from the region between the tumor and normal parenchyma. The blue dotted line shows the border between the tumor and the normal brain tissue. (d, e) HE staining (×100 and ×400) of the sample. Glioma cells (red arrow) invaded normal neuronal cells (green arrow). Neurons with morphological impairments can also be detected. The black arrow indicates the microthrombus, which was considered a characteristic of hypoxia. (f, g) HIF-1α staining (×100 and ×400) of the sample. Positive HIF-1α staining was identified in tumor cells (red arrow) and peritumor normal neurons (green arrow), which indicated that hypoxia occurred in the peritumoral region. However, HIF-1α staining was negative in neurons located away from the tumor.

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