Search Results (8)

Background: Febrile seizures are a common form of convulsions in childhood, with poorly known cellular mechanisms. The objective of this pioneering study was to provide qualitative and quantitative ultrastructural research on the large neuronal perikarya in the cerebellar dentate nucleus (DN), using an experimental model of hyperthermia-induced seizures (HSs), comparable to febrile seizures in children. Methods: The study used young male Wistar rats, divided into experimental and control groups. The HSs were evoked by a hyperthermic water bath at 45 °C for 4 min for four consecutive days. Specimens (1 mm³) collected from the DN were routinely processed for transmission electron microscopy studies. Results: The ultrastructure of the large neurons in the DN affected by hyperthermic stress showed variously pronounced lesions in the perikarya, including total cell disintegration. The most pronounced neuronal lesions exhibited specific morphological signs of aponecrosis, i.e., dark cell degeneration (‘dark neurons’). In close vicinity to the ‘dark neurons’, the aponecrotic bodies were found. The findings of this qualitative ultrastructural study correspond with the results of the morphometric analysis of the neuronal perikarya. Conclusions: Our results may constitute interesting comparative material for similar submicroscopic observations on large DN neurons in HS morphogenesis and, in the future, may help to find potential treatment targets to prevent febrile seizures or reduce recurrent seizures in children. Full article

Caffeine is a psychoactive substance that is widely consumed by individuals of various demographics, including pregnant women. It can readily cross the blood–brain and placental barriers, easily reaching the fetal brain. In addition, caffeine has also shown antioxidant properties, as its consumption reduces oxidative stress in various pathologies, including epilepsy. Febrile seizures (FS) are among the most common convulsive disorders in infants and young children. Here, we used an animal model of FS to learn whether maternal caffeine (1 g/L) intake consumption during gestation and lactation could exert beneficial effects on the rat cortex. Neonatal development was analyzed by measuring pinna opening, eye opening, righting reflex on the surface, and geotaxis reflex. Five and twenty days after HIS, the rats were euthanized, and plasma membranes and cytosolic fractions were isolated from their cortex brain. The enzymatic activities of glutathione reductase, glutathione S-transferase, Na⁺/K⁺-ATPase, and Mg²⁺-ATPase, as well as the levels of thiobarbituric acid reacting substances, were quantified. Results showed that maternal caffeine intake eliminates oxidative stress and normalizes Na⁺/K⁺-ATPase activity disrupted by HIS and also affects some parameters relating to the neurodevelopment of neonates. As FS in infants has been related to epilepsy in adults, the antioxidant properties of caffeine could prevent potential damage from hyperthermia. Full article

Febrile seizures (FSs) are a relatively common early-life condition that can cause CNS developmental disorders, but the specific mechanisms of action of FS are poorly understood. In this work, we used hyperthermia-induced FS in 10-day-old rats. We demonstrated that the efficiency of glutamatergic synaptic transmission decreased rapidly after FS by recording local field potentials. This effect was transient, and after two days there were no differences between control and post-FS groups. During early ontogeny, the proportion of calcium-permeable (CP)-AMPA receptors in the synapses of the principal cortical and hippocampal neurons is high. Therefore, rapid internalization of CP-AMPA receptors may be one of the mechanisms underlying this phenomenon. Using the whole-cell patch-clamp method and the selective CP-AMPA receptor blocker IEM-1460, we tested whether the proportion of CP-AMPA receptors changed. We have demonstrated that FS rapidly reduces synaptic CP-AMPA receptors in both the hippocampus and the entorhinal cortex. This process was accompanied by a sharp decrease in the calcium permeability of the membrane of principal neurons, which we revealed in experiments with kainate-induced cobalt uptake. Our experiments show that FSs cause rapid changes in the function of the glutamatergic system, which may have compensatory effects that prevent excessive excitotoxicity and neuronal death. Full article

Febrile seizures (FS) are one of the most common seizure disorders in childhood which are classified into short and prolonged, depending on their duration. Short FS are usually considered as benign. However, epidemiological studies have shown an association between prolonged FS and temporal lobe epilepsy. The development of animal models of FS has been very useful to investigate the mechanisms and the consequences of FS. One of the most used, the “hair dryer model”, has revealed that prolonged FS may lead to temporal lobe epilepsy by altering neuronal function. Several pieces of evidence suggest that Na⁺/ K⁺-ATPase and Mg²⁺-ATPase may play a role in this epileptogenic process. In this work, we found that hyperthermia-induced seizures (HIS) significantly increased the activity of Na⁺/ K⁺-ATPase and Mg²⁺-ATPase five and twenty days after hyperthermic insult, respectively. These effects were diminished in response to AMPA, D₂ dopamine A₁ and A_2A receptors activation, respectively. Furthermore, HIS also significantly increased the protein level of the AMPA subunit GluR1. Altogether, the increased Na⁺/ K⁺-ATPase and Mg²⁺-ATPase agree well with the presence of protective mechanisms. However, the reduction in ATPase activities in the presence of NMDA and AMPA suggest an increased propensity for epileptic events in adults. Full article

Prolonged neonatal febrile seizures (FSs) often lead to cognitive decline and increased risk of psychopathology in adulthood. However, the neurobiological mechanisms underlying the long-term adverse effects of FSs remain unclear. In this study, we exposed rat pups to hyperthermia and induced FSs lasting at least 15 min. We investigated the short-term (one day) and delayed (11–13 and 41–45 days) effects of FSs on some parameters of morphological and functional maturation in the hippocampus. We noticed that FSs altered the developmental pattern of glial fibrillary acidic protein (GFAP) immunoreactivity. In rats aged 21–23 days, GFAP-positive astrocytes covered a smaller area, and their morphological characteristics resembled those of rats at 11 days of age. In post-FS rats, the magnitude of long-term synaptic potentiation was reduced compared to control animals of the same age. Applying the gliotransmitter D-serine, an agonist of the glycine site of NMDA receptors, restored LTP to control values. A decrease in LTP amplitude was correlated with impaired spatial learning and memory in the Barnes maze task in post-FS rats. Our data suggest that impaired neuron–glia interactions may be an essential mechanism of the adverse effects of FS on the developing brain. Full article

The objective of this pioneering study was to assess potentially neuroprotective properties of topiramate (TPM), a broad spectrum and newer-generation antiepileptic used against damage to synaptic endings of the temporal lobe neocortex in experimental hyperthermia-induced seizures (HS). TPM (80 mg/kg b.m.) was administered in young male Wistar rats with an intragastric tube before and immediately after HS. Specimens (1 mm³) collected from the neocortex, fixed via transcardial perfusion with paraformaldehyde and glutaraldehyde solution, were routinely processed for transmission-electron microscopic study, i.e., for descriptive and morphometric analysis. The ultrastructure of neocortical neuropil components affected by hyperthermic stress showed distinct swelling of pre and post-synaptic axodendritic and axospinal endings, including total disintegration. Mitochondria were markedly damaged in synaptic structures. Axoplasm of presynaptic boutons contained a decreased number of synaptic vesicles. Synaptic junctions showed active zone-shortening. Preventive administration of TPM before HS induction demonstrated neuroprotective effects against synaptic damage in approximately 1/4 of these structures. Interestingly, beneficial effects on synapsis morphology were more common in perivascular zones close to well-preserved capillaries. They were demonstrated by smaller swelling of both presynaptic and postsynaptic parts, well-preserved mitochondria, an increased number and regular distribution of synaptic vesicles within axoplasm, and a significantly increased synaptic active zones. However, topiramate used directly after HS was ineffective in the prevention of hyperthermia-evoked synaptic injury. Our findings support the hypothesis that topiramate applied before HS can protect some neocortical synapses via the vascular factor by enhancing blood–brain barrier components and improving the blood supply of gray matter in the temporal lobe, which may be significant in febrile seizure-prevention in children. Full article

Febrile seizures (FSs) in early life are significant risk factors of neurological disorders and cognitive impairment in later life. However, existing data about the impact of FSs on the developing brain are conflicting. We aimed to investigate morphological and functional changes in the hippocampus of young rats exposed to hyperthermia-induced seizures at postnatal day 10. We found that FSs led to a slight morphological disturbance. The cell numbers decreased by 10% in the CA1 and hilus but did not reduce in the CA3 or dentate gyrus areas. In contrast, functional impairments were robust. Long-term potentiation (LTP) in CA3-CA1 synapses was strongly reduced, which we attribute to the insufficient activity of N-methyl-D-aspartate receptors (NMDARs). Using whole-cell recordings, we found higher desensitization of NMDAR currents in the FS group. Since the desensitization of NMDARs depends on subunit composition, we analyzed NMDAR current decays and gene expression of subunits, which revealed no differences between control and FS rats. We suggest that an increased desensitization is due to insufficient activation of the glycine site of NMDARs, as the application of D-serine, the glycine site agonist, allows the restoration of LTP to a control value. Our results reveal a new molecular mechanism of FS impact on the developing brain. Full article

Aim: The aim of the paper is to study the prevalence of Dravet Syndrome (DS) in the Polish population and indicate different factors other than seizures reducing the quality of life in such patients. Method: A survey was conducted among caregivers of patients with DS by the members of the Polish support group of the Association for People with Severe Refractory Epilepsy DRAVET.PL. It included their experience of the diagnosis, seizures, and treatment-related adverse effects. The caregivers also completed the PedsQL survey, which showed the most important problems. The survey received 55 responses from caregivers of patients with DS (aged 2–25 years). Results: Prior to the diagnosis of DS, 85% of patients presented with status epilepticus lasting more than 30 min, and the frequency of seizures (mostly tonic-clonic or hemiconvulsions) ranged from 2 per week to hundreds per day. After the diagnosis of DS, patients remained on polytherapy (drugs recommended in DS). Before diagnosis, some of them had been on sodium channel blockers. Most patients experienced many adverse effects, including aggression and loss of appetite. The frequency of adverse effects was related to the number of drugs used in this therapy, which had an impact on the results of the PedsQL form, particularly in terms of the physical and social spheres. Intensive care unit stays due to severe status epilepticus also had an influence on the results of the PedsQL form. Conclusions: Families must be counseled on non-pharmacologic strategies to reduce seizure risk, including avoidance of triggers that commonly induce seizures (including hyperthermia, flashing lights and patterns, sleep abnormalities). In addition to addressing seizures, holistic care for a patient with Dravet syndrome must involve a multidisciplinary team that includes specialists in physical, occupational and speech therapy, neuropsychology, social work. Full article