Apoptosis in the Dentate Nucleus Following Kindling-induced Seizures in Rats.

BACKGROUND: Epilepsy is a common neurological disorder characterized by abnormal and recurrent neuronal discharges that result in epileptic seizures. The dentate nuclei of the cerebellum receive excitatory input from different brain regions. Purkinje cell loss due to chronic seizures could lead to decreased inhibition of these excitatory neurons, resulting in the activation of apoptotic cascades in the dentate nucleus. OBJECTIVE: The present study was designed to determine whether there is a presence of apoptosis (either intrinsic or extrinsic) in the dentate nucleus, the final relay of the cerebellar circuit, following kindling-induced seizures. METHODS: In order to determine this, seizures were triggered via the amygdaloid kindling model. Following 0, 15, or 45 stimuli, rats were sacrificed, and the cerebellum was extracted. It was posteriorly prepared for the immunohistochemical analysis with cell death biomarkers: TUNEL, Bcl-2, truncated Bid (tBid), Bax, cytochrome C, and cleaved caspase 3 (active form). Our findings reproduce results obtained in other parts of the cerebellum. RESULTS: We found a decrease of Bcl-2 expression, an anti-apoptotic protein, in the dentate nucleus of kindled rats. We also determined the presence of TUNEL-positive neurons, which confirms the presence of apoptosis in the dentate nucleus. We observed the expression of tBid, Bax, as well as cytochrome C and cleaved caspase-3, the main executor caspase of apoptosis. CONCLUSION: There is a clear activation of both the intrinsic and extrinsic apoptotic pathways in the cells of the dentate nucleus of the cerebellum of rats subjected to amygdaloid kindling.

A Comprehensive Review of Neuronal Changes in Diabetics.

There has been an exponential rise in diabetes mellitus (DM) cases on a global scale. Diabetes affects almost every system of the body, and the nervous system is no exception. Although the brain is dependent on glucose, providing it with the energy required for optimal functionality, glucose also plays a key role in the regulation of oxidative stress, cell death, among others, which furthermore contribute to the pathophysiology of neurological disorders. The variety of biochemical processes engaged in this process is only matched by the multitude of clinical consequences resulting from it. The wide-ranging effects on the central and peripheral nervous system include, but are not limited to axonopathies, neurodegenerative diseases, neurovascular diseases, and general cognitive impairment. All language search was conducted on MEDLINE, COCHRANE, EMBASE, and GOOGLE SCHOLAR till September 2021. The following search strings and Medical Subject Headings (MeSH terms) were used: "Diabetes Mellitus," "CNS," "Diabetic Neuropathy," and "Insulin." We explored the literature on diabetic neuropathy, covering its epidemiology, pathophysiology with the respective molecular pathways, clinical consequences with a special focus on the central nervous system and finally, measures to prevent and treat neuronal changes. Diabetes is slowly becoming an epidemic, rapidly increasing the clinical burden on account of its wide-ranging complications. This review focuses on the neuronal changes occurring in diabetes such as the impact of hyperglycemia on brain function and structure, its association with various neurological disorders, and a few diabetes-induced peripheral neuropathic changes. It is an attempt to summarize the relevant literature about neuronal consequences of DM as treatment options available today are mostly focused on achieving better glycemic control; further research on novel treatment options to prevent or delay the progression of neuronal changes is still needed.

Epilepsy: A bibliometric analysis (1968-2020) of the Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suarez" in Mexico.

The Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez" (INNN) is one of the main institutions in Latin America treating epilepsy; and bibliometric analysis has an increasing role in analyzing the literature, acting as a Google Maps of medical research. We tracked the scientific output in Scopus and the impact of the institution from its foundation to July 2020 in the field of epilepsy. We roughly separated this group by clinical and experimental approach, identifying core journals, type of article, increase with time, and number of citations. A total of 228 papers, from a total of 3,034 produced by the INNN in that period, were found. Additionally, we identified that neurocysticercosis, pharmacology, genetics, and proteins involved in epilepsy were the most investigated topics. Also, there is a sustained growth in the number of papers per year since 1985. The number of authors per paper ranges from one to 15, and neuroscience journals are the preferred target of researchers, with a predilection for "Epilepsy and Behavior".

Caloric Restriction and Ketogenic Diet Therapy for Epilepsy: A Molecular Approach Involving Wnt Pathway and KATP Channels.

Epilepsy is a neurological disorder in which, in many cases, there is poor pharmacological control of seizures. Nevertheless, it may respond beneficially to alternative treatments such as dietary therapy, like the ketogenic diet or caloric restriction. One of the mechanisms of these diets is to produce a hyperpolarization mediated by the adenosine triphosphate (ATP)-sensitive potassium (KATP) channels (KATP channels). An extracellular increase of K+ prevents the release of Ca2+ by inhibiting the signaling of the Wnt pathway and the translocation of ß-catenin to the cell nucleus. Wnt ligands hyperpolarize the cells by activating K+ current by Ca2+. Each of the diets described in this paper has in common a lower use of carbohydrates, which leads to biochemical, genetic processes presumed to be involved in the reduction of epileptic seizures. Currently, there is not much information about the genetic processes implicated as well as the possible beneficial effects of diet therapy on epilepsy. In this review, we aim to describe some of the possible genes involved in Wnt pathways, their regulation through the KATP channels which are implicated in each one of the diets, and how they can reduce epileptic seizures at the molecular level.