Anticonvulsant Effects of Topiramate and Lacosamide on Pilocarpine-Induced Status Epilepticus in Rats: A Role of Reactive Oxygen Species and Inflammation

Background: Status epilepticus (SE) is a neurological disorder characterized by a prolonged epileptic activity followed by subsequent epileptogenic processes. The aim of the present study was to evaluate the early effects of topiramate (TPM) and lacosamide (LCM) treatment on oxidative stress and inflammatory damage in a model of pilocarpine-induced SE. Methods: Male Wistar rats were randomly divided into six groups and the two antiepileptic drugs (AEDs), TPM (40 and 80 mg/kg, i.p.) and LCM (10 and 30 mg/kg, i.p.), were injected three times repeatedly after pilocarpine administration. Rats were sacrificed 24 h post-SE and several parameters of oxidative stress and inflammatory response have been explored in the hippocampus. Results: The two drugs TPM and LCM, in both doses used, succeeded in attenuating the number of motor seizures compared to the SE-veh group 30 min after administration. Pilocarpine-induced SE decreased the superoxide dismutase (SOD) activity and reduced glutathione (GSH) levels while increasing the catalase (CAT) activity, malondialdehyde (MDA), and IL-1β levels compared to the control group. Groups with SE did not affect the TNF-α levels. The treatment with a higher dose of 30 mg/kg LCM restored to control level the SOD activity in the SE group. The two AEDs, in both doses applied, also normalized the CAT activity and MDA levels to control values. In conclusion, we suggest that the antioxidant effect of TPM and LCM might contribute to their anticonvulsant effect against pilocarpine-induced SE, whereas their weak anti-inflammatory effect in the hippocampus is a consequence of reduced SE severity.     

A low external temperature method for synthesis of active electrode materials for Li batteries – Part B: Synthesis of lithium iron oxides Li x Fe y O z

Anode materials for lithium-ion batteries based on iron oxides were synthesized using two different methods: a Low External Temperature Method (LETM) and a conventional Solid State Reaction Method (SSRM). Both methods lead to the formation of final products representing a mixture of two phases: approximately 75% LiFeO₂ and 25% Li_−x Fe₅O₈ (0  <  x ≤ 0.1). When compared with the ordinary solid state synthesis, LETM creates conditions for carrying out the synthesis at a lower external calcination temperature (200 °C) over a shorter period. The properties of the Li _x Fe _y O _z obtained by the LETM were compared with those of the same compound obtained by SSR at 700 °C. Higher initial discharge capacity was displayed by the sample synthesized by the SSR method, while a superior cycling stability was shown by the sample synthesized by the LETM. The latter shows approximately double capacity at the 30th cycle as compared with the sample synthesized by SSRM.     

Iron-based composite oxides as alternative negative electrodes for lithium-ion batteries

Nanosized lithiated iron oxides with 10 and 50 wt.% SiO₂ were prepared by a sol–gel method using 1 M Fe(NO₃)₃ · 9H₂O and 1 M LiNO₃ aqueous solutions in a stoichiometric ratio of 1:1 and colloidal silica. Dried xerogel was calcinated at 700 °C for 4 h in air. The X-ray data of samples synthesized using 10% and 50% SiO₂ showed the presence of a mixture of two phases: α-LiFeO₂ and Li_1−x Fe₅O₈ (0 < x ≤ 0.1) for a sample containing 10% SiO₂ and LiFe(SiO₃)₂ and Fe₂O₃ (h) for a sample with 50% SiO₂. The electrochemical behaviour of the compounds was investigated galvanostatically within the 0.01–3.0 V range at a current density of 0.80 mA cm⁻². The Li/Li _x Fe _y O _z (10%) · SiO₂ cell showed a high initial reversible capacity of 1,080 mA h g⁻¹ and a capacity of 600 mA h g⁻¹ at the 30th cycle. Accounting these results is the presence of a SiO₂ phase which stabilizes the structure of the active mass on cycling. The mean charge voltage (1.8 V) and the discharge voltage of 1.0 V versus Li⁺ reference electrode as well as the high reversible capacity indicate that this material is suitable for use as anode in lithium-ion batteries.     

Pre- and Post-Endurance Training Mitigates the Rat Pilocarpine-Induced Status Epilepticus and Epileptogenesis-Associated Deleterious Consequences

Epilepsy is a brain disorder characterized by recurrent epileptic seizures and neurobiological, physiological, mood, and cognitive consequences. In the last decade, the beneficial effects of regular physical exercise have been investigated in patients with neurodegenerative diseases such as epilepsy. However, data on its beneficial effects and underlying mechanisms are still insufficient. The objective of the current study was to investigate the effects of endurance training, applied before and after pilocarpine (Pilo) administration, on status epilepticus (SE) severity, and its relation to epileptogenesis deleterious consequences during the chronic epileptic phase. Long-term aerobic training, applied four weeks before SE and eight weeks after SE, elevated the threshold to induce SE and reduced spontaneous motor seizures. The protective effect of this alternative approach on seizure susceptibility resulted in improved memory responses, and alleviated comorbid depression in epileptic rats. The exercised epileptic rats had improved markers of oxidative stress by decreasing lipid peroxidation and increasing the levels of glutathione and activity of superoxide dismutase in the rat hippocampus. Aerobic training managed to ameliorate the neuroinflammation by decreasing the levels of TNF-α and IL-1β in the hippocampus. Our results suggest that regular physical training predisposes the subjects to crucial plastic changes, leading to increased resistance to SE and the development of epileptogenesis.     

Effects of Lacosamide Treatment on Epileptogenesis,Neuronal Damage and Behavioral Comorbidities in a Rat Model of Temporal Lobe Epilepsy

Clinically, temporal lobe epilepsy (TLE) is the most prevalent type of partial epilepsy and often accompanied by various comorbidities. The present study aimed to evaluate the effects of chronic treatment with the antiepileptic drug (AED) lacosamide (LCM) on spontaneous motor seizures (SMS), behavioral comorbidities, oxidative stress, neuroinflammation, and neuronal damage in a model of TLE. Vehicle/LCM treatment (30 mg/kg, p.o.) was administered 3 h after the pilocarpine-induced status epilepticus (SE) and continued for up to 12 weeks in Wistar rats. Our study showed that LCM attenuated the number of SMS and corrected comorbid to epilepsy impaired motor activity, anxiety, memory, and alleviated depressive-like responses measured in the elevated plus maze, object recognition test, radial arm maze test, and sucrose preference test, respectively. This AED suppressed oxidative stress through increased superoxide dismutase activity and glutathione levels, and alleviated catalase activity and lipid peroxidation in the hippocampus. Lacosamide treatment after SE mitigated the increased levels of IL-1β and TNF-α in the hippocampus and exerted strong neuroprotection both in the dorsal and ventral hippocampus, basolateral amygdala, and partially in the piriform cortex. Our results suggest that the antioxidant, anti-inflammatory, and neuroprotective activity of LCM is an important prerequisite for its anticonvulsant and beneficial effects on SE-induced behavioral comorbidities.     

The Role of Melatonin on Behavioral Changes and Concomitant Oxidative Stress in icvAβ1-42 Rat Model with Pinealectomy

One of the pathological hallmarks of Alzheimer’s disease (AD) associated with its progression that contributes to β-amyloid (Aβ) generation is oxidative stress (OS). Clinical data suggest that melatonin is a potent antioxidant that might be effective in the adjunctive therapy of this neurodegenerative disease. The present study aimed to explore the role of melatonin on behavioral changes and markers of OS in three rat models, namely, pinealectomy (pin) model of melatonin deficit, intracerebroventricular (icv)Aβ_1-42 model of AD, and combination of both pin and Aβ_1-42 model (pin+icvAβ_1-42). The chronic injection with vehicle/melatonin (50 mg/kg, i.p. for 40 days) started on the same day of sham/pin and icv vehicle/Aβ_1-42 infusion procedures. Anxiety in the open field and the elevated plus-maze test and cognitive responses in the object recognition test were tested between the 30th–35th day after the surgical procedures. Markers of OS in the frontal cortex (FC) and hippocampus were detected by the ELISA method. Melatonin treatment corrected the exacerbated anxiety response only in the pin+icvAβ_1-42 model while it alleviated the cognitive impairment in the three models. Pinealectomy disturbed the antioxidant system via enhanced SOD activity and decreased GSH levels both in the FC and hippocampus. The Aβ_1-42 model decreased the SOD activity in the FC and elevated the MDA level in the two brain structures. The pin+icvAβ_1-42 model impaired the antioxidant system and elevated lipid peroxidation. Melatonin supplementation restored only the elevated MDA level of icvAβ_1-42 and pin+icvAβ_1-42 model in the hippocampus. In conclusion, our study reveals that the pin+icvAβ_1-42 rat model triggers more pronounced anxiety and alterations in markers of OS that may be associated with melatonin deficit concomitant to icvAβ_1-42-induced AD pathology.     

Impact of Melatonin Deficit on Emotional Status and Oxidative Stress-Induced Changes in Sphingomyelin and Cholesterol Level in Young Adult,Mature, and Aged Rats

The pineal gland regulates the aging process via the hormone melatonin. The present report aims to evaluate the effect of pinealectomy (pin) on behavioral and oxidative stress-induced alterations in cholesterol and sphingomyelin (SM) levels in young adult, mature and aging rats. Sham and pin rats aged 3, 14 and 18 months were tested in behavioral tests for motor activity, anxiety, and depression. The ELISA test explored oxidative stress parameters and SM in the hippocampus, while total cholesterol was measured in serum via a commercial autoanalyzer. Mature and aged sham rats showed low motor activity and increased anxiety compared to the youngest rats. Pinealectomy affected emotional responses, induced depressive-like behavior, and elevated cholesterol levels in the youngest rats. However, removal of the pineal gland enhanced oxidative stress by diminishing antioxidant capacity and increasing the MDA level, and decreased SM level in the hippocampus of 14-month-old rats. Our findings suggest that young adult rats are vulnerable to emotional disturbance and changes in cholesterol levels resulting from melatonin deficiency. In contrast, mature rats with pinealectomy are exposed to an oxidative stress-induced decrease in SM levels in the hippocampus.     

Synthesis and features of binary cobaltite spinels

The main developments in the synthesis of cobaltites are surveyed. Solid state reactions between oxides, thermal decomposition of mechanical mixtures of transition metal salts, the use of complex compounds as precursors, mechanochemical synthesis, deposition of cobaltites on supports and cobaltite synthesis by thermal treatment of coprecipitated compounds are discussed and the specific advantages and disadvantages of each method pointed out. The binary spinel cobaltites find applications as materials in many fields, their main importance being as catalysts. In order to achieve high specific surface area, cobaltite synthesis by thermal treatment of coprecipitated precursors proves to be the most promising method. Different kinds of precursors are regarded. Transition metal basic salts are promising for the synthesis of binary mixed oxides and, in particular, of cobaltites. The conditions suited by the coprecipitated precursors for the synthesis of cobaltites with preset properties, such as high-dispersity, homogeneity, a definite stoichiometry and a low impurity content, are indicated. Special attention is paid to hydroxidecarbonates. Their use as precursors ensures these demands for the final product and also evolution of toxic gases during the thermal decomposition is avoided.     

Arachidonate-induced thrombosis in mice: effects of gender or testosterone and estradiol administration

Sodium arachidonate (i.v.) has previously been shown to induce pulmonary emboli formation and a dose dependent cyanosis and respiratory depression in mice. Subsequently, we found that male mice are significantly more sensitive to arachidonate than females. Aspirin given orally 2 hours prior to arachidonate administration inhibits the responses of both males and females. Pretreatment with depo-testosterone markedly increases the effect of arachidonate in both males and females and depo-estradiol pretreatment reduces the responses in all mice. This exacerbation by testosterone of the arachidonate response and the attenuating effects of estradiol is consistent with data reported using other thrombogenic techniques.