Introduction: Temporal Lobe Epilepsy (TLE) is a disorder caused by neuronal electrical imbalance, clinically manifested by spontaneous and recurrent seizures1,2. Its pathogenesis involves channelopathies of calcium channels, which contributes to hyperexcitability and hypersynchrony in TLE3 . About 30% of patients do not respond to drug treatment4 , making it necessary to develop new therapeutic alternatives, such as cell therapy. This work aimed to evaluate the modulation of mesenchymal stem cells (MSCs) in the calcium channel CACNA1G (Cav3.1) gene expression. Methods: MSCs were extracted from Wistar rats bone marrow and then cultured and transplanted intravenously and intranasally in the control and epileptic groups. The brain was collected 1 and 7 days after transplantation to analyze gene expression. Results: The analysis showed that treated animals had greater gene expression, compared to animals not treated in the epileptic and control group, in both days and administration routes. Furthermore, epileptic animals that were not treated had a low or negative expression of the gene. The epileptic rats that were treated, on the other hand, had a marked increase in gene expression e in the prefrontal cortex. Conclusion: This up-regulation noted on the treated groups raises the hypothesis that MSCs would be using these channels to modify the microenvironment5 , intensifying Cav.3.1 transcription and contributing to tissue regeneration by neurodifferentiation6,7. This is supported by the increase in the calcium influx present in the early stages of neuronal maturation8,9. Thus, MSCs can modulate gene expression in the pilocarpine-induced animal’s brain, making Cav3.1 a target to be explored in epilepsy.

Background: Temporal Lobe Epilepsy (TLE), by firing of neuronal populations, leads to spontaneous and recurrent seizures1 . As 30% of TLE patients do not respond to pharmacotherapy2,3, it is necessary to search for alternatives. Mesenchymal stem cells (MSCs) are an attractive approach in this context, due to their less invasive character and its ability to modulate diseased niches. Objective: Analyze the gene expression related to the cation-chloride cotransporter KCC2 in TLE induced by pilocarpine model in rats. Design and Setting: Experimental study, Brain Institute of Rio Grande do Sul. Methods: MSCs were extracted from the bone marrow of Wistar rats, cultured and transplanted intravenously and intranasally into healthy and epileptic Wistar rats. Results: It was observed a decrease in the expression of KCC2 in the brain of the animals at 1-day post-transplant, which refers to a down-regulation, and an increase at 7 days post-transplant, representing an up-regulation. The loss of function of KCC2 decreases the release of chloride with difficulty in inhibiting GABAergic inhibition, resulting in hyperexcitability of neuronal circuits. In this case, MSCs can promote rearrangement in gamma-aminobutyric acid-mediated inhibition, reducing hyperexcitability and hypersynchronicity. Hence, KCC2 down-regulation is associated with epileptiform activity, while up-regulation can be related to the MSCs effects. Also, KCC2 expression showed a kind of pattern at 1-day post- transplant in both routes of administration, providing the possibility that KCC2 can be explored as a biomarker for epilepsy. Conclusion: KCC2 is an important target for epilepsy, as well MSCs have a modulatory function on the levels of the expression of this gene in animals induced to status epilepticus by pilocarpine.

Background: Infection by Zika virus (ZIKV) is associated with damage to the Central Nervous System, such as Congenital Zika Syndrome1 . Due to its transplacental transmission, ZIKV induces neuroinflammation and microglial activation, resulting in lesions that can compromise neurodevelopment2-4. The fetus protection can be provided by maternal antibodies. However, this protection is still controversial5 . In this context, it is necessary to elucidate the effects of ZIKV and the mechanisms involved. Objectives: The present work aim to evaluate the role of the ZIKV+IgG+ complex in murine microglia cells (BV2). Design and setting: BV2 were exposed for 24 or 72 hours, to ZIKV, ZIKA-IgG+ or ZIKV+IgG+ complex. Methods: Effects of exposure to treatments were evaluated by MTT, oxidation of DCFHDA (ROS production)6 and mitochondrial membrane potential (Δ∴ϑ), measured by JC-17 assay. Results: It was observed that ZIKV-IgG+ and the ZIKV+IgG+ complex are cytotoxic to microglia, impairing the viability of these cells, altering Δ∴ϑ and inducing the production of ROS, especially in long-term exposure8,9. Negative action mediated by these antibodies may be a result of oxidative stress and a intervention in the Δ∴ϑ. Conclusion: ZIKV-IgG+ antibodies are harmful to microglia and these mechanisms may be related to the potential for ZIKV neuroinflammation.

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Objective The transsphenoidal surgery is a safe and effective technique to manage different skull base pathologies, such as pituitary adenomas. The purpose of the present study is to describe the initial experience with endoscopic transsphenoidal surgery in the treatment of pituitary adenoma patients at a tertiary hospital that is a reference in neurosurgery in Southern Brazil. Materials and Methods We retrospectively analyzed data from 60 patients with pituitary adenoma who underwent endoscopic transsphenoidal surgery between 2012 and 2019. Demographic characteristics, type of tumor, baseline hormonal changes, and clinical presentation were reported, as well as postoperative outcomes, tumor resection rate, and complications. Results The male/female ratio was of 0.53:1, and the mean age of the sample was of 54 (range: 26 to 79) years. In total, 34 patients (57%) presented the non-functioning adenoma subtype, and 26 (43%), the functioning adenoma subtype. In the non-functioning and functioning subtype groups, the average tumor diameter was of 32 mm and 18 mm, and the mean follow-up was of 27 months and 32 months respectively. Regarding visual symptoms, 79% of the patients showed improvement after surgery. Hormonal remission was achieved in 71% of the patients with prolactinoma, 85% of those with cushing, and 57% of patients with acromegaly. Overall, gross total resection (GTR) was achieved in 50% of patients but with a significantly lower rate among patients with tumors with parasellar growth (high grade on the Knosp classification). The most prevalent surgical complications observed were postoperative cerebrospinal fluid (CSF) leak and meningitis in 11% and 6% of the cases respectively. Conclusion We have shown that transsphenoidal endoscopic surgery can produce good results in the management of pituitary adenomas, with acceptable peri- and postoperative morbidity and mortality. Regardless of the technique used, the presence of large and giant pituitary adenomas with a high Knosp grade represents an enormous challenge for contemporary neurosurgery.