Repetitive transcranial magnetic stimulation in murine models of epilepsy: A systematic review of methodological aspects and outcomes.

OBJECTIVES: Clinical studies of repetitive transcranial magnetic stimulation (rTMS) do not provide consistent efficacy results, possibly due to variability in methodological parameters. Our aim is to systematically review preclinical rTMS protocols in murine models of epilepsy, offering insights from might facilitate the optimization of clinical trials. METHODS: We searched MEDLINE, SCOPUS and Web of Science from inception until December 2023, including English-written and peer-reviewed studies with clinical or electroencephalographic (EEG) outcomes. RESULTS: Among 480 search results, in the 23 eligible studies both mice and rats were used. Epilepsy induction methods included injections of pentylenetetrazole, kainic acid, picrotoxin and lithium-pilocarpine, electrical kindling (amygdala/ventral hippocampus), electroconvulsive shock and genetic models of absence and temporal lobe epilepsy. For motor threshold (MT) definition electromyography with motor evoked potentials and single-pulse TMS were used. Stimulation intensity ranged between 40 % and 200 % of MT or 0.125-2.5 T. High-frequency rTMS (≥5 Hz) demonstrated either no effect on seizure suppression or a rather facilitatory effect, promoting ictogenesis, with the exception of 20-Hz-rTMS coupling with lorazepam for status epilepticus cessation. Low-frequency rTMS (<5 Hz), primarily at 0.5 and 1 Hz, exerted an inhibitory effect on both clinical and EEG parameters on various epilepsy models in most studies and also significantly ameliorated performance in behavioral tests. CONCLUSIONS: rTMS holds potential for effective neuromodulation, that is critically dependent on stimulation frequency and epilepsy type. Translational knowledge gained from preclinical protocols may inform and optimize rTMS application for epilepsy management in future clinical trials.

Role of Memantine in Limiting Cochleotoxicity in Rats.

Οur aim was to test whether amikacin's well-known cochleotoxic effects could be suppressed, depending on whether an NMDA-antagonist (memantine) was administered simultaneously with or after amikacin treatment. Forty Wistar rats were used in this experiment. Ten rats acted as controls and received no medication (group A). Amikacin (200 mg/kg) was administered intraperitoneally (i.p.) once daily for 14 days to 10 animals in group B; amikacin (200 mg/kg) was administered concurrently with memantine (10 mg/kg, i.p., once daily) to the same 10 animals in group C. Group D was given intraperitoneal memantine (10 mg/kg, once daily) for 14 days following a 2-week amikacin treatment. The cochlear activity of the right ear was tested using DPOAE in conscious animals. All animals were sacrificed at the conclusion of the experiment and both cochleae were collected for histological and immunohistochemical analysis. All groups treated with amikacin showed decreased cochlear activity, as testified by decreased DPOAE-amplitudes compared to the pre-treatment state. In the rats of group B, the DPOAE reduction was more pronounced. On histologic exam, the cochlear structures of group C rats and, although to a lesser extent, group D rats showed less severe cochlea damage. Memantine plays a protective role, resulting in restoring partially cochlear structures when administered either simultaneously with or after completion of amikacin i.p. treatment in rats.

Predictors of influenza vaccination among elderly: a cross-sectional survey in Greece.

BACKGROUND: Senior individuals are particularly vulnerable to influenza. Research suggests that protection against the virus and its transmission in this high-risk group of the population can be achieved by active immunization against the pathogen. AIMS: To explore and analyze the attitudes, knowledge and behavior of people over the age of 60 on influenza vaccination. POPULATION AND METHODS: This cross-sectional survey included people over the age of 60 who were eligible candidates for the influenza vaccine from 3 regions from Northern and 1 region from Southern Greece. A self-completed questionnaire based upon the Theory of Planned Behaviour, the Motivation for Vaccination (MoVac-flu) and the Vaccination Advocacy Scale (MovAd) was administered to the participants. Demographic characteristics and information about health status were also obtained. RESULTS: The final sample included 318 participants with mean age of 70.7 years. More than half of the participants (56.6%) had received a flu vaccine in 2018 while 50.8% received it annually in previous years. Behavioral (p < 0.001), normative (p < 0.001), and control beliefs (p < 0.001), promoted the uptake of the vaccine and the increased intention score (p < 0.001) was associated with increased probability of vaccination. Greater age (p = 0.001) and frequent visits to the doctors (p = 0.003) had a positive influence upon the uptake of the vaccine. CONCLUSIONS: Only a small proportion of those over the age of 60 had received the influenza vaccine. This finding is worrying, as it indicates the impact that a future outbreak of seasonal influenza could exert upon vulnerable groups. There is an urgent need for further, better and more evidence-based information from healthcare professionals to achieve greater vaccination coverage in the community.

Dexmedetomidine effects in different experimental sepsis in vivo models.

Sepsis is a major cause of death and the most common cause of death among critically ill, non-ICU patients. Dexmedetomidine (DEX), an 2 adrenergic receptor agonist, presents sympatholytic action in certain parts of the brain with anxiolytic, sedative, and pain killing effects. Additionally, through the activation of 7 nicotinic acetylcholine receptor receptors, DEX reduces cytokine transcription and inhibits inflammation, rendering it beneficial during septic conditions. Moreover, there is a lot of interest in designing experimental sepsis models, where the administration of DEX is evaluated for its impact on multiple systems. This review focuses on experimental studies published between 1999 to March 2019 that were using DEX administration in sepsis in vivo models. From these, 36 articles were selected and summarized. Overall results show evidence that DEX may decrease mortality and inhibit inflammation, as it enhances the activity of the immune system while reducing its systemic reaction and lowering cytokine concentrations. Moreover DEX succeeds to alleviate heart injury during sepsis, acting beneficially for microcirculation and shows a neuroprotective role by inhibiting apoptotic pathways. In addition, DEX appears to have a protective role for liver and spleen as well as a beneficial role for the function of lungs and kidneys as it reduces sepsis-induced injuries and apoptosis in intra-abdominal experimental sepsis models.

Fentanyl and naloxone effects on glutamate and GABA release rates from anterior hypothalamus in freely moving rats.

Fentanyl, a µ-opioid receptor agonist, has been studied for its neuro/psycho-pharmacological effects since its first clinical use; however, its effect on the release rate of the Central Nervous System (CNS) neurotransmitters has not been yet elucidated. In the present study the influence of fentanyl on the release rates of glutamate and GABA is investigated. Specifically, we examined the effects of intravenous (10 µg/kg) as well as intrahypothalamic (0.1nmol/min) fentanyl administration on the release rates of GABA and glutamate in the superfusate of anterior hypothalamus, under tail pinch manipulation. The release rate of the neurotransmitters was monitored by the push-pull superfusion technique. To investigate the role of fentanyl the opioid antagonist, naloxone 0.1 mg/kg was administered intravenously, or 50nmol/min intrahypothalamicaly. The amino acids were determined by High Performance Liquid Chromatography (HPLC) and fluorimetric detection after NBD-Cl derivatisation. After intravenous fentanyl administration a significant decrease of glutamate and increase of GABA release rates were observed. However during the pain manipulations, the release rate of glutamate was increased. Intravenous naloxone did not affect significantly the release rates of both amino acids, while intrahypothalamic antagonist administration reversed the alterations in both neurotransmitters release rates. Our results demonstrate that there is an opioid-glutamatergic transmission pathway, located in hypothalamus and that opioids can activate NMDA receptors, thus reducing the nociceptive threshold and the opioid analgesic effect.