RESUMO
Epilepsy, characterized by recurrent seizures and abnormal brain discharges, is the third most common chronic disorder of the Central Nervous System (CNS). Although significant progress has been made in the research on antiepileptic drugs (AEDs), approximately one-third of patients with epilepsy are refractory to these drugs. Thus, research on the pathogenesis of epilepsy is ongoing to find more effective treatments. Many pathological mechanisms are involved in epilepsy, including neuronal apoptosis, mossy fiber sprouting, neuroinflammation, and dysfunction of neuronal ion channels, leading to abnormal neuronal excitatory networks in the brain. CK2 (Casein kinase 2), which plays a critical role in modulating neuronal excitability and synaptic transmission, has been shown to be associated with epilepsy. However, there is limited research on the mechanisms involved. Recent studies have suggested that CK2 is involved in regulating the function of neuronal ion channels by directly phosphorylating them or their binding partners. Therefore, in this review, we will summarize recent research advances regarding the potential role of CK2 regulating ion channels in epilepsy, aiming to provide more evidence for future studies.
RESUMO
SLIT and NTRK-like protein-5 (SLITRK5) is one of the six members of SLITRK protein family, which is widely expressed in central nervous system (CNS). In brain, SLITRK5 plays important roles in neurite outgrowth, dendritic branching, neuron differentiation, synaptogenesis, and signal transmission of neurons. Epilepsy is a common, chronic neurological disorder characterized by recurrent spontaneous seizures. The pathophysiological mechanism of epilepsy remains unclear. Neuronal apoptosis, abnormal nerve excitatory transmission, and synaptic remodeling are thought to be involved in the development of epilepsy. To explore whether there is a potential relationship between SLITRK5 and epilepsy, we investigated the expression and distribution of SLITRK5 in patients with temporal lobe epilepsy (TLE) and a rat model of epilepsy. We collected cerebral cortex samples from patients with drug-refractory temporal lobe epilepsy, and a rat model of epilepsy induced by lithium chloride/pilocarpine was established. The ways of immunohistochemistry, double-immunofluorescence labeling and western blot have been used in our study to research the expression and distribution of SLITRK5 in the temporal lobe epilepsy patients and epilepsy animal model. All of the results have shown that SLITRK5 is mainly localized in the cell cytoplasm of neurons both in patients with TLE and in epilepsy model. In addition, compared with nonepileptic controls, the expression of SLITRK5 was upregulated in the temporal neocortex of TLE patients. And both in the temporal neocortex and hippocampus of pilocarpine-induced epilepsy rats, the expression of SLITRK5 was increased at 24 h after status epilepticus (SE), with a relatively high level within 30 days, and reached the peak on the 7th day after SE. Our preliminary results revealed that SLITRK5 may have a potential relationship with epilepsy, which may be a foundation for the further study of the underlying mechanism between SLITRK5 and epilepsy and the therapeutic targets of antiepileptic drugs.
Assuntos
Epilepsia do Lobo Temporal , Epilepsia , Neocórtex , Animais , Ratos , Modelos Animais de Doenças , Epilepsia/induzido quimicamente , Epilepsia/metabolismo , Epilepsia do Lobo Temporal/induzido quimicamente , Hipocampo/metabolismo , Neocórtex/metabolismo , Pilocarpina/toxicidade , Pilocarpina/metabolismo , Ratos Sprague-Dawley , Convulsões/metabolismo , Regulação para CimaRESUMO
Adamantinomatous craniopharyngioma (ACP) presents a significant challenge to neurosurgeons despite its benign histology due to its aggressive behavior and unique growth patterns. This narrative review explores the evolving landscape of ACP treatments and their efficacy, highlighting the continuous development in therapeutic approaches in recent years. Traditionally, complete resection was the primary treatment for ACP, but surgical -related morbidity have led to a shift. The invasive nature of the finger-like protrusions in the histological structure results in a higher recurrence rate for ACP compared to papillary craniopharyngioma (PCP), even after complete macroscopic resection. Given this, combining subtotal resection with adjuvant radiotherapy has shown potential for achieving similar tumor control rates and potentially positive endocrine effects. Simultaneously, adjuvant treatments (such as radiotherapy, intracystic treatment, and catheter implantation) following limited surgery offer alternative approaches for sustained disease control while minimizing morbidity and alleviating clinical symptoms. Additionally, advances in understanding the molecular pathways of ACP have paved the way for targeted drugs, showing promise for therapy. There is a diversity of treatment models for ACP, and determining the optimal approach remains a subject of ongoing debate in the present context. In order to achieve a good-term quality of life (QOL), the main goal of the cyst disappearance or reduction of surgical treatment is still the main. Additionally, there should be a greater emphasis on personalized treatment at this particular stage and the consideration of ACP as a potentially chronic neurosurgical condition. This review navigates the evolving landscape of ACP therapies, fostering ongoing discussions in this complex field.
RESUMO
INTRODUCTION: Total resection of cystic craniopharyngiomas is challenging, especially for some large cystic tumors, because it is often associated with high recurrence and morbidity rates. Minimally invasive cyst decompression and continuous drainage are appropriate to manage clinical symptoms. We reviewed our experience of the past 11 years to determine the long-term effects of neuroendoscopic surgery (NES) combined with Ommaya reservoir (OR) for the treatment of cystic craniopharyngiomas. METHODS: We retrospectively analyzed the data of 15 adult patients with cystic craniopharyngiomas at a single institution with the primary goal to evaluate the treatment mode with initial adequate decompression of the cyst under visualization and continuous drainage. The study endpoints were functional outcome, cyst volume changes, and tumor progression. RESULTS: The median follow up was 77 (20-136) months. Clinical symptoms, e.g. increased intracranial pressure and visual impairment, could be rapidly improved after NES. The postoperative reduction in cyst volume (p < 0.001) and improvement in Karnofsky performance status (p < 0.001) were significant, and long-term tumor control was achieved in 10 patients (67%). Aspiration from the OR after progression of the tumor's cystic portion remains a major option, with only few patients requiring repeat NES procedures. No patient developed acute or severe clinical symptoms during follow up. CONCLUSIONS: NES could decompress the craniopharyngioma cyst under visualization and enable faster clinical-symptom improvement. The minimally invasive NES combined with OR allowed long-term symptom control in most patients without surgery-related injury. This palliative treatment strategy could be an alternative modality for cystic craniopharyngioma treatment.
RESUMO
SLIT and NTRK-like protein-5 (SliTrk5) is one of the six members of SliTrk protein family, which is widely expressed in the central nervous system (CNS), regulating and participating in many essential steps of central nervous system development, including axon and dendritic growth, neuron differentiation, and synaptogenesis. SliTrk5, as a neuron transmembrane protein, contains two important conservative domains consisting of leucine repeats (LRRs) located at the amino terminal in the extracellular region and tyrosine residues (Tyr) located at the carboxyl terminal in the intracellular domains. These special structures make SliTrk5 play an important role in the pathological process of the CNS. A large number of studies have shown that SliTrk5 may be involved in the pathogenesis of CNS diseases, such as obsessive-compulsive-disorder (OCD), attention deficit/hyperactivity disorder (ADHD), glioma, autism spectrum disorders (ASDs), and Parkinson's disease (PD). Targeting SliTrk5 is expected to become a new target for the treatment of CNS diseases, promoting the functional recovery of CNS. The purpose of this article is to review the current research progression of the role of SliTrk5 in CNS and its potential mechanisms in CNS diseases.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Sistema Nervoso Central , Proteínas de Membrana , Proteínas do Tecido Nervoso , Transtorno Obsessivo-Compulsivo , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Sistema Nervoso Central/metabolismo , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Transtorno Obsessivo-Compulsivo/metabolismoRESUMO
Background: The dementia and affective disorders are common non-motor features in patients with essential tremor (ET). However, the relationship of ET with cognitive impairments and affective disorders remains controversial. This meta-analysis aimed to analyze the association of ET with dementia and affective disorders. Methods: Original studies published from January 1999 to October 2019 were systematically searched from the database of Medline (OvidSP), EMBASE (OvidSP), and the Cochrane Central Register of Controlled Trials. Pooled standard mean difference (SMD, random effect model), odds ratios (ORs), relative risk (RR), and 95% CI were calculated. Results: Compared with the Non-ET group, patients with ET had significantly lower Mini-Mental State Examination (MMSE) score (SMD, -1.16; 95% CI, -1.75 to -0.58; p = 0.0001) and had significantly higher depressive and anxiety symptoms scale score (SMD, 0.55; 95% CI, 0.22-0.87; p = 0.0009). The OR for dementia and affective disorders in individuals with ET compared with individuals without ET was 2.49 (95% CI, 2.17-2.85, p < 0.00001). While there was no significant difference in Montreal Cognitive Assessment (MoCA) score between ET and Non-ET groups (SMD, -0.52; 95% CI, -0.16 to 0.13; p = 0.23), there was a significant difference in the risk of mortality between ET and Non-ET groups (RR = 4.69, 95% CI, 2.18-10.07). Conclusion: The non-motor symptoms should not be neglected among patients with ET. However, the causal relationship between ET and dementia, depression, and anxiety is unclear.
RESUMO
Pediatric craniopharyngioma is typically characterized by cystic changes and calcifications. It can grow from the suprasellar area to the posterior fossa (4%). This work reports that it is very rare for craniopharyngioma to grow from the suprasellar area to or beyond the level of the foramen magnum. Twelve patients with this disease have undergone one or several microsurgeries, and the microsurgical approaches are different. Among them, two cases died, and most of the remaining patients had certain complications such as endocrine dysfunction, nerve palsy, and subdural effusion. We treated two patients whose tumors had grown to the level of the foramen magnum, one of which reached C2 levels. Both cases were treated with a neuroendoscopy. There were no deaths and no complications. Our cases are the longest follow-up of this type of craniopharyngioma.