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// Giovanna Casili 1 , Maria Caffo 2 , Michela Campolo 1 , Valeria Barresi 3 , Gerardo Caruso 2 , Salvatore M. Cardali 2 , Marika Lanza 1 , Raffaella Mallamace 4 , Alessia Filippone 1 , Alfredo Conti 2 , Antonino Germano 2 , Salvatore Cuzzocrea 1 and Emanuela Esposito 1 1 Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy 2 Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Unit of Neurosurgery, University of Messina, Messina, Italy 3 Department of Human Pathology, University of Messina, Messina, Italy 4 Unit of Anesthesia, University of Messina, Messina, Italy Correspondence to: Emanuela Esposito, email: eesposito@unime.it Keywords: glioblastomas; TLR-4; Wnt; Dkk-3; claudin-5 Received: February 19, 2018 Accepted: December 13, 2018 Published: December 25, 2018 ABSTRACT Purpose: Glioblastomas are highly aggressive brain tumors. Various pathways are involved in gliomagenesis, among which the Wingless (Wnt) signaling. Dickkopf protein-related protein 3 (Dkk-3) interacts with proteins of Wnt pathwayas inhibitor. The Wnt signaling contributes to activity of the claudins, that are critical components of tight junctions, whose expression was altered selectively in cerebral microvessels of glioblastoma. The aim of this study was to determine the role of Wnt pathways in the regulation of tumor growth, apoptosis process by targeting Dkk-3, tight junctions alteration involving claudin-5, suggesting possible therapeutic interactions involving Wnt/Toll-like receptors (TLRs) pathways. Results: We showed a significant decreasing of Dkk-3 and claudin-5 in human glioblastoma cell lines, as well as in U-87 MG xenograft tumors and in glioblastoma human patient’s tissues, with an involvement of the apoptosis process. Also, an interesting TLR-4/Wnt modulation highlighted that the absence of TLR-4 determined resistance to the tumor onset. Conclusions: We concluded that combined modulation of Wnt/Dkk-3/claudin-5 and TLR-4 pathways, simultaneously targeting apoptosis and survival signaling defects, might shift the balance from tumor growth stasis to cytotoxic therapeutic responses, flowing in greater therapeutic benefits. Methods: In the present study we investigated the expression of Dkk-3, claudin-5, apoptosis markers and TLR-4 receptor protein levels in in vitro studies on U-138MG, A-172, LN-18 and LN-229 human glioblastoma cell lines, and in vivo study using TLR-4 KO mice and in glioblastoma human patient’s tissues.

Spinal tumor (ST) surgery carries the risk of new neurological deficits in the postoperative period. Intraoperative neurophysiological monitoring and mapping (IONM) represents an effective method of identifying and monitoring in real time the functional integrity of both the spinal cord (SC) and the nerve roots (NRs). Despite consensus favoring the use of IONM in ST surgery, in this era of evidence-based medicine, there is still a need to demonstrate the effective role of IONM in ST surgery in achieving an oncological cure, optimizing patient safety, and considering medicolegal aspects. Thus, neurosurgeons are asked to establish which techniques are considered indispensable. In the present study, the authors focused on the rationale for and the accuracy (sensitivity, specificity, and positive and negative predictive values) of IONM in ST surgery in light of more recent evidence in the literature, with specific emphasis on the role of IONM in reducing the incidence of postoperative neurological deficits. This review confirms the role of IONM as a useful tool in the workup for ST surgery. Individual monitoring and mapping techniques are clearly not sufficient to account for the complex function of the SC and NRs. Conversely, multimodal IONM is highly sensitive and specific for anticipating neurological injury during ST surgery and represents an important tool for preserving neuronal structures and achieving an optimal postoperative functional outcome.

Holmes tremor is characterized by irregular resting, postural and intention tremors. Deep brain stimulation (DBS) is an effective treatment. A 34-year-old man with Holmes tremor, secondary to head trauma, became agitated during DBS performed under local anesthesia. Remifentanil 0.03 µg/kg/min provided effective sedation and DBS was safety and successful performed. J Curr Surg. 2015;5(4):207-208 doi: http://dx.doi.org/10.14740/jcs288e