Detection of glioblastoma multiforme using quantitative molecular magnetic resonance imaging based on 5-aminolevulinic acid: in vitro and in vivo studies.

OBJECTIVES: We demonstrated a novel metabolic method based on sequential administration of 5-aminolevulinic acid (ALA) and iron supplement, and ferric ammonium citrate (FAC), for glioblastoma multiforme (GBM) detection using R2' and quantitative susceptibility mapping (QSM). MATERIALS AND METHODS: Intra-cellular iron accumulation in glioblastoma cells treated with ALA and/or FAC was measured. Cell phantoms containing glioblastoma cells and Wistar rats bearing C6 glioblastoma were imaged using a 3 T MRI scanner after sequential administration of ALA and FAC. The relaxivity and QSM analysis were performed on the images. RESULTS: The intra-cellular iron deposition was significantly higher in the glioma cells with sequential treatment of ALA and FAC for 6 h compared to those treated with the controls. The relaxivity and magnetic susceptibility values of the glioblastoma cells and rat brain tumors treated with ALA + FAC (115 ± 5 s-1 for R2', and 0.1 ± 0.02 ppm for magnetic susceptibility) were significantly higher than those treated with the controls (55 ± 18 (FAC), 45 ± 15 (ALA) s-1 for R2', p < 0.05, and 0.03 ± 0.03 (FAC), 0.02 ± 0.02 (ALA) ppm for magnetic susceptibility, p < 0.05). DISCUSSION: Sequential administration of ALA and iron supplements increases the iron deposition in glioblastoma cells, enabling clinical 3 T MRI to detect GBM using R2' or QSM.

Hydrogel-encapsulated extracellular vesicles for the regeneration of spinal cord injury.

Spinal cord injury (SCI) is a critical neurological condition that may impair motor, sensory, and autonomous functions. At the cellular level, inflammation, impairment of axonal regeneration, and neuronal death are responsible for SCI-related complications. Regarding the high mortality and morbidity rates associated with SCI, there is a need for effective treatment. Despite advances in SCI repair, an optimal treatment for complete recovery after SCI has not been found so far. Therefore, an effective strategy is needed to promote neuronal regeneration and repair after SCI. In recent years, regenerative treatments have become a potential option for achieving improved functional recovery after SCI by promoting the growth of new neurons, protecting surviving neurons, and preventing additional damage to the spinal cord. Transplantation of cells and cells-derived extracellular vesicles (EVs) can be effective for SCI recovery. However, there are some limitations and challenges related to cell-based strategies. Ethical concerns and limited efficacy due to the low survival rate, immune rejection, and tumor formation are limitations of cell-based therapies. Using EVs is a helpful strategy to overcome these limitations. It should be considered that short half-life, poor accumulation, rapid clearance, and difficulty in targeting specific tissues are limitations of EVs-based therapies. Hydrogel-encapsulated exosomes have overcome these limitations by enhancing the efficacy of exosomes through maintaining their bioactivity, protecting EVs from rapid clearance, and facilitating the sustained release of EVs at the target site. These hydrogel-encapsulated EVs can promote neuroregeneration through improving functional recovery, reducing inflammation, and enhancing neuronal regeneration after SCI. This review aims to provide an overview of the current research status, challenges, and future clinical opportunities of hydrogel-encapsulated EVs in the treatment of SCI.

ß2-Adrenergic Receptor Stimulation Upregulates Cx43 Expression on Glioblastoma Multiforme and Olfactory Ensheathing Cells.

Glioblastoma multiforme (GBM) is described as an invasive astrocytic tumor in adults. Despite current standard treatment approaches, the outcome of GBM remains unfavorable. The downregulation of connexin 43 (Cx43) expression is one of the molecular transformations in GBM cells. The Cx43 levels and subsequently gap junctional intercellular communication (GJIC) have an important role in the efficient transfer of cytotoxic drugs to whole tumor cells. As shown in our previous study, the stimulation of the ß2-adrenergic receptor (ß2-AR) leads to the modulation of Cx43 expression level in the GBM cell line. Here we further examine the effect of clenbuterol hydrochloride as a selective ß2-AR agonist on the Cx43 expression in human GBM-derived astrocyte cells and human olfactory ensheathing cells (OECs) as a potent vector for future gene therapy. In this experiment, first we established a primary culture of astrocytes from GBM samples and verified the purity using immunocytofluorescent staining. Western blot analysis was performed to evaluate the Cx43 protein level. Our western blot findings reveal that clenbuterol hydrochloride upregulates the Cx43 protein level in both primary human astrocyte cells and human OECs. Conversely, ICI 118551 as a ß2-AR antagonist inhibits these effects. Moreover, clenbuterol hydrochloride increases the Cx43 expression in primary human astrocyte cells and OECs co-culture systems, and ICI 118551 reverses these effects. To confirm the western blot results, immunocytofluorescent staining was performed to evaluate the ß2-AR agonist effect on Cx43 expression. Our immunocytofluorescent results supported western blot analysis in primary human astrocyte cells and the OECs co-culture system. The results of this study suggest that the activation of ß2-AR with regard to Cx43 protein levels enhancement in GBM cells and OECs might be a promising approach for GBM treatment in the future.

The Optimal Surgical Approach for Treatment of Chronic Subdural Hematoma: Questionnaire Assessment of Practice in Iran and Review of Literature.

Chronic subdural hematoma (CSDH) is a curable entity frequently encountered by neurosurgeons. The present study was conducted to explore expert opinion and common practice in Iran. Besides, a Review of randomized clinical trials in literature was performed. A questionnaire including six questions discussing major aspects of practice on CSDH, with multiple choices was designed. A pilot study was performed for reliability analysis of the questionnaire. A total of 100 neurosurgeons were selected randomly from the members of Iranian Association of Neurological Surgeons. Frequency of answers to each item, differences in response rates and correlation of various categories were analyzed using Chi-square statistics. The mean duration of experience was 15.4 ± 5 years, with a range of 10 to 37 years. The most common initial procedure of choice was burr-hole drainage (64%). At recurrent cases, surgical approach was changed to craniotomy at one-third of those treated initially with burr-hole drainage. The participants believed that surgical technique was predictive of outcome and recurrence. Burr-hole without drainage was used by less expert neurosurgeons (mean 12.5 ± 6), however, burr-hole drainage was the dominant technique at more than 15 years of experience and craniectomy was used only by participants with more than 30 years of experience (10%). Irrigation was used by most of the neurosurgeons (87.5%) in combination with drainage and burr-hole. The majority of participants used flat position at the postoperative period. At the current study, the pattern of management for CSDH was similar to other reports at literature suggesting the burr-hole drainage and irrigation as optimal treatment. Individualized decision-making could be made at challenging cases.

The use of low- dose intrathecal fluorescein in endoscopic repair of cerebrospinal fluid rhinorrhea.

BACKGROUND: Intrathecal injection of fluorescein is a useful adjuvant method for localization of fistulas in endoscopic endonasal repair of cerebrospinal fluid (CSF) leakage. Although being neurotoxic in commercial doses, a low dose of diluted fluorescein seems to be safe on the basis the existing data in the literature. OBJECTIVES: The purpose of this study was to investigate the role of a low- dose intrathecal fluorescein injection in detection of CSF fistula and potential adverse effects of this technique. MATERIALS AND METHODS: CSF rhinorrhea was repaired in 20 patients with an endoscopic endonasal technique. Intraoperative intrathecal fluorescein injection was used for localization of the site of the CSF leak. The accuracy rate of leakage site identification and the incidence of complications and recurrences were recorded. RESULTS: Intrathecal administration of fluorescein demonstrated CSF leakage in 18 of the 20 patients (90%). There were no intraoperative complications. Definitive closure of the CSF leakage site was achieved in 16 patients (80%) after the initial reconstruction. Recurrence occurred in four cases and all patients were free of CSF leakage after the second surgical attempt. CONCLUSIONS: The present study suggested that a low dose of intraoperative intrathecal fluorescein administration is a safe and sensitive method for localization of CSF leakage sites.