Antiseizure Effects of Peganum harmala L. and Lavandula angustifolia.

Peganum harmala L. and Lavandula angustifolia are two traditional herbs with probable antiseizure effects. This study evaluated the effects of these two herbal extracts on pentylenetetrazol- (PTZ-) induced seizures in mice. We prepared hydroalcoholic extracts using P. harmala seeds and the aerial parts of L. angustifolia and then randomly divided 190 mice into 19 groups. Normal saline (10 mg/kg), diazepam (2 mg/kg), P. harmala (2.5, 5, 10, 15, 30, 45, and 60 mg/kg), and L. angustifolia (200, 400, 600, and 800 mg/kg) were intraperitoneally (IP) administrated 30 min before an IP administration of PTZ (90 mg/kg). Animals were observed for behavioral changes for one hour. In addition, the effects of flumazenil and naloxone on the antiseizure activity of P. harmala and L. angustifolia were assessed. P. harmala showed antiseizure activity at the dose of 10 mg/kg; it prolonged the seizure latency and decreased the seizure duration. The mortality protection rate was 90% for this herbal extract. L. angustifolia (600 mg/kg) prolonged the seizure latency and decreased both seizure duration and mortality. Neither flumazenil nor naloxone significantly reversed the antiseizure activities of P. harmala and L. angustifolia. In mice, the hydroalcoholic extracts of P. harmala and L. angustifolia showed antiseizure activity against PTZ-induced seizures. We could not delineate the exact antiseizure mechanisms of these extracts in the current study.

The Effect of Different Concentrations of Methylprednisolone on Survival, Proliferation, and Migration of Neural Stem/Progenitor Cells.

Introduction: The present study addressed whether methylprednisolone (MP) as an anti-inflammatory drug used in neurodegenerative diseases and neural stem/progenitor cells (NS/PCs) is safe. Methods: First, embryonic rat NS/PCs were exposed to different concentrations of MP, and then we evaluated their survival by MTT assay, proliferation by analyzing the number and diameter of neurospheres, and the migration of the cells by neurosphere assay. Results: The viability of NS/PCs was reduced following exposure to 10, 15, and 20 µg/mL of MP. In addition, although the number of neurospheres did not change, exposure to different concentrations of MP resulted in the formation of smaller neurospheres. Despite these undesirable effects, the highest concentration of MP (20 µg/mL) increased the migration capacity of the NS/PCs. Conclusion: The combination of MP and NS/PCs is not recommended due to the adverse effects of MP on the survival and proliferation of NS/PCs. Highlights: Methylprednisolone reduced survival of neural stem/progenitor cells.Methylprednisolone decreased proliferation of neural stem/progenitor cells.The highest concentration of MP (20 µg/mL) increased the migration capacity of the neural stem/progenitor cells. Plain Language Summary: In this study, we evaluate the effect of the exposure of neural stem/progenitor cells to methylprednisolone. Based on the results, combination of neural stem/progenitor cells and methylprednisolone not recommended due to reduction of survival and proliferation of the cells.

Driving restrictions in patients with seizures; a review of the regulations from the English-speaking nations.

PURPOSE: We investigated the existing regulations about driving eligibility and restrictions for persons with seizures in all English-speaking countries in the world. We aimed to identify: 1) Is there a distinction between epilepsy and functional seizures (FS) in the regulations? 2) What is the required seizure-free period before a person with seizure regains their driving eligibility? METHODS: First, we identified all the English-speaking countries in the world. Then, we referred to the website of the Department of Motor Vehicles or its equivalent in each nation or we searched the Google engine with the name of each specific nation and "driving" and "epilepsy". RESULTS: There are 59 English-speaking countries in the world. For 37 nations, the data on regulations about driving eligibility for persons with seizures were lacking. Only the UK has made distinctions between epilepsy and FS. The required seizure-free period before a person with seizure regains their driving eligibility varied significantly between nations. Not all nations have made distinctions between private driving and commercial driving. Finally, only some nations have specific rules and regulations for different scenarios (e.g., provoked seizures vs epilepsy, or nocturnal seizures only, etc.) CONCLUSION: Many English-speaking nations in the world do not have explicit rules and regulations about driving eligibility and restrictions for persons with seizures. International scientific organizations should do more to provide appropriate and personalized guidelines for different scenarios of seizures, so the governments can adopt appropriate regulations.

Effects of FTY720 on Neural Cell Behavior in Two and Three-Dimensional Culture and in Compression Spinal Cord Injury.

Introduction: The present study aimed to evaluate the effects of FTY720 as a neuromodulatory drug on the behaviors of neural stem/progenitor cells (NS/PCs) in two-dimensional (2-D) and three-dimensional (3-D) cultures and in spinal cord injury (SCI). Methods: The NS/PCs isolated from the ganglionic eminence of the 13.5-day old embryos were cultured as free-floating spheres. The single cells obtained from the second passage were cultured in 96-well plates without any scaffold (2-D) or containing PuraMatrix (PM, 3-D) or were used for transplantation in a mouse model of compression SCI. After exposure to 0, 10, 50, and 100 nanomolar of FTY720, the survival, proliferation, and migration of the NS/PCs were evaluated in vitro using MTT assay, neurosphere assay, and migration assay, respectively. Moreover, the functional recovery, survival and migration capacity of transplanted cells exposure to 100 nanomolar FTY720 were investigated in SCI. Results: Cell survival and migration capacity increased after exposure to 50 and 100 nanomolar FTY720. In addition, higher doses of FTY720 led to the formation of more extensive and more neurospheres. Although this phenomenon was similar in both 2-D and 3-D cultures, PM induced better distribution of the cells in a 3-D environment. Furthermore, co-administration of FTY720 and NS/PCs 7 days after SCI enhanced functional recovery and both survival and migration of transplanted cells in the lesion site. Conclusions: Due to the positive effects of FTY720 on the behavior of NS/PCs, using them in combination therapies can be an appealing approach for stem cell therapy in CNS injury.

MCM2 mutation causes autosomal dominant nonsyndromic hearing loss (DFNA70): novel variant in the second family.

Pathogenic variants in MCM2 could result in mild to severe sensorineural hearing loss in the affected individuals (deafness, autosomal dominant 70; DFNA70; OMIM: 616968), an extremely rare autosomal dominant progressive disorder. Here, we report a novel missense variant (NM_004526:c.388C>T, p.R130C; Clinvar: SCV002072508) in MCM2 in an Iranian family identified by whole-exome sequencing and confirmed by Sanger sequencing. The heterozygous variant (NM_004526:c.388C>T, p.R130C) in MCM2 was identified in the proband and his mother. The proband is a nine-year-old male born to nonconsanguineous parents. The proband was characterized by nonsyndromic hearing loss, while his mother showed a mild form of the disorder. This study reports the second disease-causing variant in MCM2 in the world and confirms that hearing loss arising from variants in MCM2 is nonsyndromic. Nevertheless, as was reported in the previous family, phenotype could vary among the patients with the same variant.

Caffeinated drinks, fruit juices, and epilepsy: A systematic review.

The aim of this systematic review was to provide the required information regarding different aspects of the relationship between epilepsy/antiseizure medications and non-alcoholic drinks. The recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement were followed. MEDLINE and Scopus from the inception until 7 August 2021 were systematically searched. These key words were used: "epilepsy" OR "seizure" OR "antiepileptic" OR "antiseizure" OR "anticonvulsant" AND "coffee" OR "tea" OR "soda" OR "juice" OR "drink" OR "cola" OR "diet" (35 key word combinations). The primary search yielded 21 458 publications (PubMed, n = 4778; Scopus, n = 16 680). Only 50 studies met all the inclusion criteria and were included in the current systematic review. In total, 17 articles investigated various non-alcoholic drinks in human studies, 11 studies were case reports/series, and 22 articles were animal/in vitro studies. None of the studies provided a class 1 of evidence. There is limited evidence suggesting that certain drinks (eg, caffeinated energy drinks) might trigger seizures. Patients with epilepsy should avoid excessive consumption of certain fruit juices (eg, grapefruit, lime, pomegranate, kinnow, and star fruit) and caffeinated drinks. However, daily coffee and tea intake can be part of a healthy balanced diet, and their consumption does not need to be stopped in patients with epilepsy. Coffee/tea consumption is not harmful if consumed at levels of 200 mg (caffeine) in one sitting (about 2½ cups of coffee) or 400 mg daily (about five cups of coffee).

Long COVID syndrome-associated brain fog.

We investigated the frequency of brain fog in a large cohort of patients with documented coronavirus disease-2019 (COVID-19) who have survived the illness. We also scrutinized the potential risk factors associated with the development of brain fog. Adult patients (18-55 years of age), who were referred to the healthcare facilities anywhere in Fars province from February 19, 2020 to November 20, 2020 were included. All patients had a confirmed COVID-19 diagnosis. In a phone call, at least 3 months after their discharge from the hospital, we obtained their current information. A questionnaire was specifically designed for data collection. In total, 2696 patients had the inclusion criteria; 1680 (62.3%) people reported long COVID syndrome (LCS). LCS-associated brain fog was reported by 194 (7.2%) patients. Female sex (odds ratio [OR]: 1.4), respiratory problems at the onset (OR: 1.9), and intensive care unit (ICU) admission (OR: 1.7) were significantly associated with reporting chronic post-COVID "brain fog" by the patients. In this large population-based study, we report that chronic post-COVID "brain fog" has significant associations with sex (female), respiratory symptoms at the onset, and the severity of the illness (ICU admission).

A New and Simple Method for Spinal Cord Injury Induction in Mice.

Introduction: Spinal Cord Injury (SCI) is a devastating disease with poor clinical outcomes. Animal models provide great opportunities to expand our horizons in identifying SCI pathophysiological mechanisms and introducing effective treatment strategies. The present study introduces a new murine contusion model. Methods: A simple, cheap, and reproducible novel instrument was designed, which consisted of a body part, an immobilization piece, and a bar-shaped weight. The injury was inflicted to the spinal cord using an 8-g weight for 5, 10, or 15 minutes after laminectomy at the T9 level in male C57BL/6 mice. Motor function, cavity formation, cell injury, and macrophage infiltration were evaluated 28 days after injury. Results: The newly designed instrument minimized adverse spinal movement during injury induction. Moreover, no additional devices, such as a stereotaxic apparatus, were required to stabilize the animals during the surgical procedure. Locomotor activity was deteriorated after injury. Furthermore, tissue damage and cell injury were exacerbated by increasing the duration of weight exertion. In addition, macrophage infiltration around the injured tissue was observed 28 days after injury. Conclusion: This novel apparatus could induce a controllable SCI with a clear cavity formation in mice. No accessory elements are needed, which can be used in future SCI studies. Highlights: A simple and precise method has been introduced for creating Spinal Cord Injury (SCI) in mice by a novel device.The device consists of a body part, an immobilization piece, and a bar-shaped weight.Assessment of locomotor activity, tissue damage, and macrophage infiltration confirmed the capability of the new SCI method.Reduction of adverse spinal movements and working without any accessory elements are the key points of this new animal model of SCI. Plain Language Summary: Spinal Cord Injury (SCI) is a medical problem that can cause the permanent motor and sensory dysfunction. Traffic accidents, falls, and violence are the most frequent causes of SCI, often affecting young people. Patients and even their families may encounter other problems, including reducing life quality, psychological burden, and enormous medical costs. Despite scientific and technological advances, no effective treatment has been found for SCI. Therefore, animal models help study damage mechanisms and evaluate novel treatment strategies. All SCI research centers require an economical and reproducible device without using complex surgical procedures by experienced surgeons to minimize variations in damage to the spinal cord. In this study, a simple, cheap, and reproducible novel instrument for SCI induction is introduced. The instrument consists of various parts, including a body part, an immobilization piece, and a bar-shaped weight. An 8-g weight was used for 5, 10, or 15 minutes to inflict injury to the spinal cord. Behavioral and tissue studies indicated that SCI could be induced in rodents in different severity without other elements. This instrument can be used in future investigations for SCI studies, including tissue engineering, stem cell therapy, and drugs delivery to access effective treatment.

Risk Factors Associated with Long COVID Syndrome: A Retrospective Study.

Background: Recently, people have recognized the post-acute phase symptoms of the COVID-19. We investigated the long-term symptoms associated with COVID-19, (Long COVID Syndrome), and the risk factors associated with it. Methods: This was a retrospective observational study. All the consecutive adult patients referred to the healthcare facilities anywhere in Fars province from 19 February 2020 until 20 November 2020 were included. All the patients had a confirmed COVID-19 diagnosis. In a phone call to the patients, at least three months after their discharge from the hospital, we obtained their current information. The IBM SPSS Statistics (version 25.0) was used. Pearson Chi square, Fisher's exact test, t test, and binary logistic regression analysis model were employed. A P value of less than 0.05 was considered to be significant. Results: In total, 4,681 patients were studied, 2915 of whom (62.3%) reported symptoms. The most common symptoms of long COVID syndrome were fatigue, exercise intolerance, walking intolerance, muscle pain, and shortness of breath. Women were more likely to experience long-term COVID syndrome than men (Odds Ratio: 1,268; 95% Confidence Interval: 1,122-1,432; P=0.0001), which was significant. Presentation with respiratory problems at the onset of illness was also significantly associated with long COVID syndrome (Odds Ratio: 1.425; 95% Confidence Interval: 1.177-1.724; P=0.0001). A shorter length of hospital stay was inversely associated with long COVID syndrome (Odds Ratio: 0.953; 95% Confidence Interval: 0.941-0.965; P=0.0001). Conclusion: Long COVID syndrome is a frequent and disabling condition and has significant associations with sex (female), respiratory symptoms at the onset, and the severity of the illness.

Long COVID in children and adolescents.

BACKGROUND: To identify the prevalence and also the full spectrum of symptoms/complaints of children and adolescents who are suffering from long COVID. Furthermore, we investigated the risk factors of long COVID in children and adolescents. METHODS: All consecutive children and adolescents who were referred to the hospitals anywhere in Fars province, Iran, from 19 February 2020 until 20 November 2020 were included. All patients had a confirmed diagnosis of COVID-19. In a phone call to patients/parents, at least 3 months after their discharge from the hospital, we obtained their current status and information if their parents agreed to participate. RESULTS: In total, 58 children and adolescents fulfilled the inclusion criteria. Twenty-six (44·8%) children/adolescents reported symptoms/complaints of long COVID. These symptoms included fatigue in 12 (21%), shortness of breath in 7 (12%), exercise intolerance in 7 (12%), weakness in 6 (10%), and walking intolerance in 5 (9%) individuals. Older age, muscle pain on admission, and intensive care unit admission were significantly associated with long COVID. CONCLUSIONS: Long COVID is a frequent condition in children and adolescents. The scientific community should investigate and explore the pathophysiology of long COVID to ensure that these patients receive appropriate treatments for their condition.

Local delivery of fingolimod through PLGA nanoparticles and PuraMatrix-embedded neural precursor cells promote motor function recovery and tissue repair in spinal cord injury.

Spinal cord injury (SCI) is a devastating clinical problem that can lead to permanent motor dysfunction. Fingolimod (FTY720) is a sphingosine structural analogue, and recently, its therapeutic benefits in SCI have been reported. The present study aimed to evaluate the therapeutic efficacy of fingolimod-incorporated poly lactic-co-glycolic acid (PLGA) nanoparticles (nanofingolimod) delivered locally together with neural stem/progenitor cells (NS/PCs) transplantation in a mouse model of contusive acute SCI. Fingolimod was encapsulated in PLGA nanoparticles by the emulsion-evaporation method. Mouse NS/PCs were harvested and cultured from embryonic Day 14 (E14) ganglionic eminences. Induction of SCI was followed by the intrathecal delivery of nanofingolimod with and without intralesional transplantation of PuraMatrix-encapsulated NS/PCs. Functional recovery, injury size and the fate of the transplanted cells were evaluated after 28 days. The nanofingolimod particles represented spherical morphology. The entrapment efficiency determined by UV-visible spectroscopy was approximately 90%, and the drug content of fingolimod loaded nanoparticles was 13%. About 68% of encapsulated fingolimod was slowly released within 10 days. Local delivery of nanofingolimod in combination with NS/PCs transplantation led to a stronger improvement in neurological functions and minimized tissue damage. Furthermore, co-administration of nanofingolimod and NS/PCs not only increased the survival of transplanted cells but also promoted their fate towards more oligodendrocytic phenotype. Our data suggest that local release of nanofingolimod in combination with three-dimensional (3D) transplantation of NS/PCs in the acute phase of SCI could be a promising approach to restore the damaged tissues and improve neurological functions.

Cosmetic adverse effects of antiseizure medications; A systematic review.

BACKGROUND: We systematically reviewed the existing literature on the cosmetic adverse effects of antiseizure medications (ASMs) in order to depict a clear picture of these unwanted side effects of ASMs with a particular attention to hair loss, hirsutism, acne, and gingival hyperplasia. METHODS: This systematic review was prepared according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Scopus, MEDLINE, and Google Scholar from the inception to 25 March, 2021 were systematically searched. These key words (title/abstract) were used: "hair loss" OR "hirsutism" OR "acne" OR "gingival hyperplasia" AND "seizure" OR "epilepsy" OR "anriseizure" OR "antiepileptic". The exclusion criteria included: non-original studies, articles not in English, and animal studies. RESULTS: The primary search yielded 3938 studies; 127 studies were related to the topic and were included in the current systematic review. The most robust evidence on cosmetic adverse effects of ASMs were related to phenytoin (causing gingival hyperplasia, hirsutism, and acne) and valproate (causing hair loss and hirsutism); however, many other ASMs were also implicated in causing these cosmetic adverse effects. CONCLUSION: Antiseizure medications may be associated with various cosmetic adverse effects. Phenytoin and valproate are the most notorious ASMs in this regard; but, other ASMs have also been implicated in causing hair loss, hirsutism, acne, and gingival hyperplasia. Physicians should pay more attention to these significant adverse effects that may affect a patient's facial attractiveness, quality of life, and emotional state.

Ibrutinib reduces neutrophil infiltration, preserves neural tissue and enhances locomotor recovery in mouse contusion model of spinal cord injury.

Following acute spinal cord injury (SCI), excessive recruitment of neutrophils can result in inflammation, neural tissue loss and exacerbation of neurological outcomes. Ibrutinib is a bruton's tyrosine kinase inhibitor in innate immune cells such as the neutrophils that diminishes their activation and influx to the site of injury. The present study evaluated the efficacy of ibrutinib administration in the acute phase of SCI on neural tissue preservation and locomotor recovery. Ibrutinib was delivered intravenously at 3.125 mg/kg either immediately, 12 hours after, or both immediately and 12 hours after SCI induction in adult male C57BL/6 mice. Neutrophil influx into the lesion area was evaluated 24 hours following SCI using light microscopy and immunohistochemistry methods. Animals' body weight changes were recorded, and their functional motor recovery was assessed based on the Basso mouse scale during 28 days after treatment. Finally, spinal cord lesion volume was estimated by an unbiased stereological method. While animals' weight in the control group started to increase one week after injury, it stayed unchanged in treatment groups. However, the double injection of ibrutinib led to a significantly lower body weight compared to the control group at 4 weeks post-injury. Mean neutrophil counts per visual field and the lesion volume were significantly decreased in all ibrutinib-treated groups. In addition, ibrutinib significantly improved locomotor functional recovery in all treated groups, especially in immediate and double-injection groups. Neural tissue protection and locomotor functional recovery suggest ibrutinib treatment as a potent immunotherapeutic intervention for traumatic SCI that warrants clinical testing.

Treatment of postictal headache: a systematic review and future directions.

BACKGROUND: Postictal headache (PIH) is a common complaint among patients with epilepsy. The prevalence of PIH is 43%. In the current endeavor, we systematically reviewed the existing treatment options for PIH in order to depict the state of the field and also to propose a research agenda to advance this topic. METHODS: MEDLINE, Scopus, and Embase from the inception to 4 February, 2021 were systematically searched for related published articles. In all electronic databases, the following search strategy was implemented and these key words (in all fields) were used: "post-ictal" AND "Headache" AND "Treatment". RESULTS: The primary search yielded 626 studies; only five studies were related to the topic and were included in the current systematic review. None of these studies provided a good class of evidence. These studies suggested that flunarizine and sumatriptan may help patients with PIH. CONCLUSION: While PIH is a common and disabling condition, its treatment is overlooked by the epilepsy society. Flunarizine and sumatriptan can be good candidates to be used in future clinical trials of the treatment of PIH. To obtain the desired evidence on the efficacy of either flunarizine or sumatriptan in treating PIH in patients with epilepsy, we need well-designed, randomized controlled trials.

Effects of neural stem cell-derived extracellular vesicles on neuronal protection and functional recovery in the rat model of middle cerebral artery occlusion.

Stroke imposes a long-term neurological disability with limited effective treatments available for neuronal recovery. Transplantation of neural stem cells (NSCs) is reported to improve functional outcomes in the animal models of brain ischemia. However, the use of cell therapy is accompanied by adverse effects, so research is growing to use cell-free extracts such as extracellular vesicles (EVs) for targeting brain diseases. In the current study, male Wistar albino rats (20 months old) were subjected to middle cerebral artery occlusion (MCAO). Then, EVs (30 µg) were injected at 2 hours after stroke onset via an intracerebroventricular (ICV) route. Measurements were done at day 7 post-MCAO. EVs administration reduced lesion volume and steadily improved spontaneous locomotor activity. EVs administration also reduced microgliosis (ionized calcium-binding adaptor molecule 1 (Iba1)+ cells) and apoptotic (terminal-deoxynucleotidyl transferase mediated nick end labelling [TUNEL]) positive cells and increased neuronal survival (neuronal nuclear (NeuN)+ cells) in the ischemic boundary zone (IBZ). However, it had no effect on neurogenesis within the sub-ventricular zone (SVZ) but decreased cellular migration toward the IBZ (doublecortin (DCX)+ cells). The results of this study showed neuroprotective and restorative mechanisms of NSC-EVs administration, which may offer new avenues for therapeutic intervention of brain ischemia. SIGNIFICANCE OF THE STUDY: Based on our results, EVs administration can effectively reduce microglial density and neuronal apoptosis, thereby steadily improves functional recovery after MCAO. These findings provide the beneficial effect of NSC-EVs as a new biological treatment for stroke.

The effects of minocycline on proliferation, differentiation and migration of neural stem/progenitor cells.

Purpose: There are several attempts to enhance the capacities of neural stem/progenitor cells (NS/PCs) as a probable source of stem cell therapy for neurodegerative diseases. The evidence shows that minocycline has several non-antibacterial effects in neurodegenerative diseases. We aimed to investigate the effect of minocycline on proliferation, differentiation and migration of embryonic NS/PCs.Materials and methods: NS/PCs extracted from ganglionic eminence of 13.5-day embryonic mice were cultured according to neurosphere protocol. After second passage they were exposed to different doses of minocycline for 7 days. The number and diameter of neurospheres were assessed to evaluate their proliferation. Migration was estimated based on the distances traveled by the cells. Because of the importance of NS/PCs behaviors in 3-dimentional environment, all assessments were done in 3-dimentional and 2-dimentional cultures. Moreover, the fate of NS/PCs to neuron or glial cells was studied.Results: NS/PCs exposed to 1 µg/ml and 10 µg/ml of minocycline and those in untreated group traveled significantly longer distances compared to those treated with 50 µg/ml and 100 µg/ml of minocycline. In addition, higher doses of minocycline reduced the NS/PCs proliferation remarkably compared to control condition just in 2-D culture. However, the differentiation capacity of cells was not significantly affected by 1 and 10 µg/ml of minocycline.Conclusion: The behavior of NS/PCs depends on minocycline dose as well as the characteristics of environment.

Eucalyptol induces hyperexcitability and epileptiform activity in snail neurons by inhibiting potassium channels.

The effects of eucalyptol (1,8-cineole) were studied on the activity of central neurons of land snail Caucasotachea atrolabiata. Eucalyptol (3 mM) depolarized the membrane potential and increased the frequency of spontaneous activity in a time dependent and reversible manner. These effects were associated with suppression of afterhyperpolarization and significant reduction of amplitude and slope of rising and falling phases of action potentials. While the eucalyptol-induced suppression of action potential amplitude and rising slope were essentially dependent on membrane depolarization, its actions on repolarization slope and afterhyperpolarization were not affected by resetting the membrane potential close to the control value. These findings suggest an inhibitory action on the potassium channels that underlie repolarization and afterhyperpolarization. Eucalyptol also increased the frequency of driven action potentials but suppressed the post stimulus inhibitory period, indicating an inhibitory action on calcium-activated potassium channels. A higher concentration of eucalyptol, 5mM, reversibly changed the pattern of activity to burst firing associated with paroxysmal depolarization shift (PDS). Low doses of eucalyptol and potassium channel blockers, tetraethylammonium and 4-aminopyridine, synergistically acted to induce burst firing. At high concentration (30 mM), tetraethylammonium was able to induce burst firing and PDS. The sodium currents and ion channel phosphorylation by protein kinases A and C were not required for the eucalyptol-induced epileptiform activity, but calcium currents were essential for this action. Our findings show the excitatory and epileptogenic action of eucalyptol, which is most likely mediated through direct inhibitory action on potassium channels.