Electrodes for neural stimulation and recording are used for the treatment of neurological disorders. Their features critically depend on impedance and interaction with brain tissue. The effect of surface modification on electrode impedance was examined in vitro and in vivo after intracranial implantation in rats. Electrodes coated by electrophoretic deposition with platinum nanoparticles (NP; <10 and 50 nm) as well as uncoated references were implanted into the rat’s subthalamic nucleus. After postoperative recovery, rats were electrostimulated for 3 weeks. Impedance was measured before implantation, after recovery and then weekly during stimulation. Finally, local field potential was recorded and tissue-to-implant reaction was immunohistochemically studied. Coating with NP significantly increased electrode’s impedance in vitro. Postoperatively, the impedance of all electrodes was temporarily further increased. This effect was lowest for the electrodes coated with particles <10 nm, which also showed the most stable impedance dynamics during stimulation for 3 weeks and the lowest total power of local field potential during neuronal activity recording. Histological analysis revealed that NP-coating did not affect glial reactions or neural cell-count. Coating with NP <10 nm may improve electrode’s impedance stability without affecting biocompatibility. Increased impedance after NP-coating may improve neural recording due to better signal-to-noise ratio.

Objective: Increased amino acid transport in brain tumours is used for diagnostic purposes. It has been shown that the α-emitting radionuclide astatine-211 labeled to L-phenylalanine is taken up by glioblastoma cells. We here tested, if systemic treatment with 4-[²¹¹At] astatine-phenylalanine (At-Phe) has a beneficial effect on survival of rats with intracranial glioblastoma. Animals, methods: The rat glioblastoma cell line BT4Ca was implanted into the prefrontal cortex of female BDIX rats by stereotaxic microinjection (10 000 cells/3 μl; n = 83). 3 days after implantation At-Phe or phosphate buffered saline were injected intravenously. A third group was treated twice, i.e., on day 3 and 10. Health condition was assessed each day by using a score system. Rats were sacrificed on days 6, 10, 13 and 17 after implantation, or when showing premortal health condition to measure tumour volume and necrosis. The proliferation index (PI) was assessed after immunohistochemical staining of Ki-67. Results: Survival time of rats treated twice with At-Phe was significantly prolonged. Additionally, both At-Phe-treated groups remained significantly longer in a better health condition. Rats with poor health status had larger tumours than rats with fair health condition. Overall, irrespective of treatment the PI was reduced in rats with poor health condition. Necrosis was larger in rats treated twice with At-Phe. Conclusion: Intravenous treatment with At-Phe enhanced survival time of rats with intracranial glioblastomas and improved health condition. These results encourage studies using local treatment of intracranial glioblastoma with At-Phe, either by repeated local injection or by intracavital application after tumour resection.

Purpose: Interactions with tumor-associated microglia and macrophages (TAM) are critical for glioblastoma progression. Polysialic acid (polySia) is a tumor-associated glycan, but its frequency of occurrence and its prognostic value in glioblastoma are disputed. Through interactions with the opposing immune receptors Siglec-11 and Siglec-16, polySia is implicated in the regulation of microglia and macrophage activity. However, due to a nonfunctional SIGLEC16P allele, SIGLEC16 penetrance is less than 40%. Here, we explored possible consequences of SIGLEC16 status and tumor cell–associated polySia on glioblastoma outcome. Experimental Design: Formalin-fixed paraffin-embedded specimens of two independent cohorts with 70 and 100 patients with newly diagnosed glioblastoma were retrospectively analyzed for SIGLEC16 and polySia status in relation to overall survival. Inflammatory TAM activation was assessed in tumors, in heterotypic tumor spheroids consisting of polySia-positive glioblastoma cells and Siglec-16–positive or Siglec-16–negative macrophages, and by exposing Siglec-16–positive or Siglec-16–negative macrophages to glioblastoma cell–derived membrane fractions. Results: Overall survival of SIGLEC16 carriers with polySia-positive tumors was increased. Consistent with proinflammatory Siglec-16 signaling, levels of TAM positive for the M2 marker CD163 were reduced, whereas the M1 marker CD74 and TNF expression were increased, and CD8+ T cells enhanced in SIGLEC16/polySia double-positive tumors. Correspondingly, TNF production was elevated in heterotypic spheroid cultures with Siglec-16–expressing macrophages. Furthermore, a higher, mainly M1-like cytokine release and activating immune signaling was observed in SIGLEC16-positive as compared with SIGLEC16-negative macrophages confronted with glioblastoma cell–derived membranes. Conclusions: Collectively, these results strongly suggest that proinflammatory TAM activation causes the better outcome in patients with glioblastoma with a functional polySia-Siglec-16 axis.