Anticonvulsant activity of α-terpineol isolated from myristica fragrans in gaers model of absence epilepsy

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Epilepsy is a neurological disorder characterized by recurrent seizures resulting from excessive abnormal electrical discharges in the brain. Medicinal plants may play an invaluable role to discover the new antiepileptic drugs. The aim of the present study was to investigate the anticonvulsant activity of a-terpineol isolated from Myristica fragrans Hountt. The a-terpineol showed a significant inhibition of the seizure episodes and spikes in absence seizures model of Genetic Absence Epilepsy Rats from Strasbourg (GAERS) rats by using electroencephalography records. It showed dose-dependent anticonvulsant activity that was comparable to the known antiepileptic drug of diazepam. It showed a rapid onset and relatively short duration of anticonvulsant effects. The present findings suggest that a-terpineol might possess antiepileptic activities against the partial seizures of human because it prevented seizures in well-established genetic absence seizure animal model of GAERS rats.

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... It is revealed that inhaled FA is unlikely to be distributed systemically, due to a strong interaction and/or biotransformation occurring at the site of contact. So that exposure of animals (rats, nonhuman primates) to labelled exogenous FA resulted in the formation of labelled DNA and protein adducts at the site of contact [26,27,28]. That's why the localization of FA toxicity in the upper respiratory tract of rats and the absence of distant site toxicity are consistent with the high reactivity and rapid metabolism of inhaled FA. ...
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Formaldehyde (FA) is toxic over a range of doses. Even though at a lower concentration, FA can react with lipids, proteins, and nucleic acids which are cellular components. FA induces cellular toxic effects in the liver, lungs, kidney, and brain by damaging parenchyma and impairment functions. This study was carried out to evaluate the serum biochemical changes and cytotoxic effects on the liver, lungs, kidney, and brain in Swiss albino mice caused by FA toxicity. For this purpose, mice were divided into four equal groups i.e. Control, inhalation, oral, and intraperitoneal. The exposure groups were further divided into three subgroups which were subjected to exposure daily for 30 days in case of inhalation and oral groups and 10 days in the intraperitoneal group for acute toxic effects. After exposure, blood and tissue samples were collected and analyzed for biochemical and morphological studies. The serum biochemical parameters like Aspartate Transaminase (AST) and Alanine Transaminase (ALT) were increased significantly (P‹0.05) in mice after FA exposure. The anatomical results revealed gross morphological changes i.e. congestion and petechial hemorrhages on the liver. The study showed gross abnormalities i.e. congestion on the lungs. But no gross abnormal features observed on the kidney and brain. Histologically, the liver showed scattered lymphocytic infiltration, dilatation of sinusoids, necrosis, and degeneration of parenchymatous cells in orally exposed mice (10 mg/kg), and diffuse lymphocytic infiltration, necrosis was seen in intraperitoneally FA injected mice at the rate of 7 and 10 mg/kg body weight. In a 5 ppm treated inhaled group, lung tissue revealed hemorrhages. Kidney showed decreased Bowman's space in 10 mg/kg treated oral group and congestion, tubular necrosis, increased Bowman's space in all intraperitoneal exposure groups. In the inhaled groups, brain tissue showed degenerating neurons with either pyknotic or karyorrhectic nuclei are gradually increased in the highest concentration group. All these findings revealed that FA has irritant toxic effects on mice in a dose related manner.
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Myristica fragrans (Houtt.) is an evergreen tree native to the Maluku Islands, Indonesia. M. fragrans kernel is extensively used in Indian traditional medicines to treat various diseases. Several studies attempt to compile and interpret the pharmacological potential of Myristica fragrans (Houtt.) aqueous and various chemical extracts. Thus, the pharmacological potential of nutmeg essential oil has not been reviewed phytochemically and pharmacologically. Therefore, the present study aimed to share appropriate literature evidence regarding the plant essential oil chemical composition and therapeutic potential of Myristica fragrans essential oil (MFEO). MFEO of leaf, mace, kernel, and seed were used worldwide as potential Ayurvedic medicine and fragrance. MFEO extracted by various methods and oil yield was 0.7-3.2, 8.1-10.3, 0.3-12.5, and 6.2-7.6% in leaf, mace, seed, and kernel. The primary chemical constituents of MFEO were sabinene, eugenol, myristicin, caryophyllene, β-myrcene, and α-pinene. Clinical and experimental investigations have confirmed the antioxidant, antimicrobial, antiinflammatory, anticancer, antimalarial, anticonvul-sant, hepatoprotective, antiparasitic, insecticidal, and nematocidal activities of MFEO. It is the first attempt to compile oil yield, composition, and the biological activities of MFEO. In future, several scientific investigations are required to understand the mechanism of action of MFEO and their bioactive constituents.
The inhibitory effects of nutmeg essential oil and three components of this oil at different concentrations were tested by GABA-induced chloride current (I GABA) stimulation through gamma-aminobutyric acid type A (GABAA) receptors comprising of α1β2γ2s subtype using the two-microelectrode voltage clamp technique on Xenopus laevis oocytes. The essential oil of the kernels of Myristica fragrans was extracted by steam distillation and was analysed by gas chromatography-mass spectrometer (GC-MS) technique. A total of 16 compounds were isolated from the essential oil. The essential oil showed promising activity by enhanced I GABA up to 100% of stimulation when tested at 100 nL/mL. For dose dependent activity, α-terpineol and myristicin showed statistical significant potentiation of I GABA. α-Terpineol was found to induce an enhancement of I GABA modulation (EC5-10) by 229.6±23.8% and 326.3±43.8%, at 100 μM and 500 μM, respectively. Myristicin induced an enhancement up to 237.6±35.1% at 500 μM. In contrast, limonene exhibited weak modulation compared to GABA controls at the same concentration. The essential oil and its two components exhibited promising inhibitory activity by enhancement of I GABA that provides scientific evidence for its traditional use in the treatment of epilepsy.
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There have been numerous non-scientific reports on the behavioural effects of Asian plants in humans who consumed these plants wholly or part thereof. Knowledge passed from generation to generation informs us of plants that increase effort and stamina, such as during paddy planting after the ingestion of Mitragyna speciosa Korth (ketum) as a tea supplement. Centella asiatica and Myristica fragrans are used as herbs to improve memory and to treat epilepsy, respectively. Zizyphus mauritiana is used to treat headache and burn pain, acts as an antitussive, and reduces rigor mortis immediately after death. These plants, which have been identified to exhibit analgaesic, muscle-relaxing, and nootropic effects, may contain important bio-compounds for medicinal chemistry and pharmaceutical research in Malaysia. The electrophysiology properties of these plants and their effects on epilepsy, behaviour, and pain will lead Malaysia to future new drug discoveries.
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Retigabine [RTG (international nonproprietary name); ezogabine (EZG; U.S. adopted name)] is a first-in-class antiepileptic drug (AED) that reduces neuronal excitability by enhancing the activity of KCNQ (K(v)7) potassium (K(+)) channels. RTG/EZG has recently been approved by the European Medicines Agency and the U.S. Food and Drug Administration as adjunctive therapy in adults with partial-onset seizures. In this review we discuss the activity that RTG/EZG has demonstrated across a broad spectrum of in vitro/in vivo animal models of seizures, including generalized tonic-clonic, primary generalized (absence), and partial seizures, in addition to the compound's ability to resist and block the occurrence of seizures induced by a range of stimuli across different regions of the brain. The potency of RTG/EZG in models refractory to several conventional AEDs and the work done to assess antiepileptogenesis and neuroprotection are discussed. Studies that have evaluated the central nervous system side effects of RTG/EZG in animals are reviewed in order to compare these effects with adverse events observed in patients with epilepsy. Based on its demonstrated effect in a number of animal epilepsy models, the synergistic and additive activity of RTG/EZG with other AEDs supports its potential use in therapeutic combinations for different seizure types. The distinct mechanism of action of RTG/EZG from those of currently available AEDs, along with its broad preclinical activity, underscores the key role of KCNQ (K(v)7) K(+) channels in neuronal excitability, and further supports the potential efficacy of this unique molecule in the treatment of epilepsy.
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Terpineol, a volatile terpenoid alcohol of low toxicity, is widely used in the perfumery industry. It is an important chemical constituent of the essential oil of many plants with widespread applications in folk medicine and in aromatherapy. The effects of terpineol on the compound action potential (CAP) of rat sciatic nerve were studied. Terpineol induced a dose-dependent blockade of the CAP. At 100 microM, terpineol had no demonstrable effect. At 300 microM terpineol, peak-to-peak amplitude and conduction velocity of CAP were significantly reduced at the end of 180-min exposure of the nerve to the drug, from 3.28 +/- 0.22 mV and 33.5 +/- 7.05 m/s, respectively, to 1.91 +/- 0.51 mV and 26.2 +/- 4.55 m/s. At 600 microM, terpineol significantly reduced peak-to-peak amplitude and conduction velocity from 2.97 +/- 0.55 mV and 32.8 +/- 3.91 m/s to 0.24 +/- 0.23 mV and 2.72 +/- 2.72 m/s, respectively (N = 5). All these effects developed slowly and were reversible upon 180-min washout.
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In Genetic Absence Epilepsy Rats from Strasbourg (GAERS), age-related absence seizures start to appear from postnatal day (PN) 30 concomitant with 'spike and wave discharges' (SWDs) appearing on cortical EEG recordings. The aim of this study was to investigate the effect of early chronic levetiracetam (LEV) treatment on the development of SWDs in young and adult GAERS. From PN 23 until PN 60, LEV (54 mg/kg, i.p.) was administered once daily to GAERS (n=8), while control GAERS (n=7) received saline (0.9% NaCl, i.p.). All animals were implanted with four epidural EEG electrodes at PN 51. EEG was recorded for 3h daily, during the last 4 days of the treatment (PN 57-PN 60) and during 4 additional days after treatment had been terminated (PN 61-PN 64). The animals were monitored again at the age of 4 months (PN 120-PN 124), about 2 months after the last administration of LEV. During treatment, epileptiform events in the LEV group were significantly reduced (62%, P<0.05) in comparison with the control group. During the following 4 days, epileptiform events were reduced in the LEV group, with an average difference of 53% (P=0.064). Once the animals had reached adult age, there was no difference in epileptiform events between the LEV group and controls. In this study, chronic LEV administration induced a reduction in epileptiform events in young GAERS. This effect persisted to some extent after treatment cessation (PN 61-PN 64), which might indicate a slowing down of epileptogenic processes. However, at the age of 4 months all animals revealed a similar expression of epileptiform discharges.
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Long-term EEG monitoring in chronically epileptic animals produces very large EEG data files which require efficient algorithms to differentiate interictal spikes and seizures from normal brain activity, noise, and, artifact. We compared four methods for seizure detection based on (1) EEG power as computed using amplitude squared (the power method), (2) the sum of the distances between consecutive data points (the coastline method), (3) automated spike frequency and duration detection (the spike frequency method), and (4) data range autocorrelation combined with spike frequency (the autocorrelation method). These methods were used to analyze a randomly selected test set of 13 days of continuous EEG data in which 75 seizures were imbedded. The EEG recordings were from eight different rats representing two different models of chronic epilepsy (five kainate-treated and three hypoxic-ischemic). The EEG power method had a positive predictive value (PPV, or true positives divided by the sum of true positives and false positives) of 18% and a sensitivity (true positives divided by the sum of true positives and false negatives) of 95%, the coastline method had a PPV of 78% and sensitivity of 99.59, the spike frequency method had a PPV of 78% and a sensitivity of 95%, and the autocorrelation method yielded a PPV of 96% and a sensitivity of 100%. It is possible to detect seizures automatically in a prolonged EEG recording using computationally efficient unsupervised algorithms. Both the quality of the EEG and the analysis method employed affect PPV and sensitivity.
Objective: To investigate anticonvulsant, cataleptic and sedative properties of n-hexane fraction of acetone insoluble part of petroleum ether extract of Myristica fragrans (MF) seeds. Methods: The anticonvulsant activity of MF (10, 30, 100 mg/kg i.p.) was studied against seizures induced by maximum electroshock (MES), pentylenetetrazol (PTZ), picrotoxin, and lithium sulphate-pilocarpine nitrate (Li-Pilo). The effect on gross behaviour, motor coordination, haloperidol-induced catalepsy (using Bar test) and pentobarbitone-induced sleep was studied. Results: MF inhibited seizures induced by MES, PTZ, and Li-Pilo. However, picrotoxin-induced seizures were not inhibited. The haloperidol-induced catalepsy was potentiated but motor coordination and pentobarbitone-induced sleep were not affected significantly. Conclusion: MF has complex actions on the central nervous system. Although it exhibited anticonvulsant activity against MES, PTZ and lithium-pilocarpine, it failed to inhibited picrotoxin-induced seizures. MF reduced central dopaminergic activity but was without any effect on pentobarbitone-induced sleep.
Aberrant transients in the cortical electroencephalogram of rats of the epileptic WAG/Rij strain were studied by means of spectial analysis. The EEG of rats of this strain contains, besides normal sleep spindles, high-voltage spiky phenomena, epileptic spike-wave discharges, and deviant intermediate stage. Spectral analysis of these transient phenomena shows that some features, like their peak frequency, are alike, but that they differ in other spectral characteristics, as in the first harmonic of the peak frequency and in the domain of the high frequencies. The results provide arguments for the view that spike-wave discharges might be considered as unique aberrant phenomena, presumably related but dissimilar to the high-voltage spiky phenomena and intermediate stage. Next to this, spectral analysis was used to study the intraphenomenal dynamics of spike-wave discharges. The peak frequency was found to decrease monotonously from about 10 Hz at the beginning of the spike-wave discharge to about 8 Hz at the end. Other spike-wave discharge frequency bands showed an intraphenomenal increase followed by a decrease. These time-variant EEG dynamics in spike-wave discharges might correlate with the cognitive disturbances during absence seizures in man.
This review summarizes the literature on anticonvulsant activities of 334 medicinal plants used for the treatment of epilepsy and convulsive disorders in the indigenous system of medicine. Data on plants which have not yet been investigated for pharmacological activity are also presented. The details are presented in a tabular form. The data includes the plant part involved, the nature of the extract or fraction used and the names of active compounds and their structures wherever available. The terms used in ancient texts for various types of convulsive disorders are retained. The results of anticonvulsant activities of extracts, fractions and pure compounds isolated from the plants on various bioassays are also presented.
The ACLAM Analgesia Task Force was appointed by ACLAM President Diane Gaertner in 2003. The charge to the Task Force was to develop guidelines that could be used by veterinarians, scientists and IACUCs in helping to provide appropriate assessment and management of pain in rodents, with the understanding that ultimately the clinical veterinarian on site at the institution must make decisions relevant to a specific animal or animals and/or protocol. The guidelines were not to be developed as, and should not be used as, requirements. To complete its charge the Task Force reviewed and cited, in a comprehensive manner, available data-based literature in writing the paper. In the course of completion of the document, ACLAM Board of Directors (BOD) reviewed an early draft and at that time also appointed 3 ACLAM diplomates with particular expertise in assessment and management of pain in rodents to act as reviewers of the draft. The Task Force members responded to the critiques and comments submitted by both the BOD and the 3 reviewers. This revised draft was then placed on the ACLAM website for comments from the entire College. The draft was well received by responding diplomates. Comments from the membership were reviewed and discussed by the Task Force, and most were incorporated into the final draft manuscript. The draft then received final review and editing by the ACLAM Publications Committee Chairman, and was accepted in the format presented here. Despite this extensive vetting process through ACLAM, readers should nonetheless be aware that because this document represents the approved statement of an AALAS affiliate organization, it has not undergone the usual JAALAS peer review process. I would like to acknowledge the efforts of the Task Force and the leadership of ACLAM for supporting this comprehensive and informative synthesis. The document should serve as a resource to the research community for years to come.
Since the early 1990s, many new antiepileptic drugs (AEDs) that offer appreciable advantages in terms of their favourable pharmacokinetics, improved tolerability and lower potential for drug-drug interactions have entered the market. However, despite the therapeutic arsenal of old and new AEDs, approximately 30% of patients with epilepsy still suffer from seizures. Thus, there remains a substantial need for the development of more efficacious AEDs for patients with refractory seizures. Here, we briefly review the emerging knowledge on the pathological basis of epilepsy and how it might best be used in the design of new therapeutics. We also discuss the current approach to AED discovery and highlight some of the unique features of newer models of pharmacoresistance and epileptogenesis that have emerged in recent years.
The purpose of this study was to investigate the anticonvulsant activity of the volatile oil of nutmeg, the dried seed kernel of Myristica fragrans Houtt, using well-established animal seizure models and to evaluate its potential for acute toxicity and acute neurotoxicity. The volatile oil of nutmeg (nutmeg oil) was tested for its effects in maximal electroshock, subcutaneous pentylenetetrazole, strychnine and bicuculline seizure tests. All the experiments were performed at the time of peak effect of nutmeg oil. Nutmeg oil showed a rapid onset of action and short duration of anticonvulsant effect. It was found to possess significant anticonvulsant activity against electroshock-induced hind limb tonic extension. It exhibited dose dependent anticonvulsant activity against pentylenetetrazole-induced tonic seizures. It delayed the onset of hind limb tonic extensor jerks induced by strychnine. It was anticonvulsant at lower doses, whereas weak proconvulsant at a higher dose against pentylenetetrazole and bicuculline induced clonic seizures. Nutmeg oil was found to possess wide therapeutic margin, as it did not induce motor impairment when tested up to 600 microL/kg in the inverted screen acute neurotoxicity test. Furthermore, the LD(50) (2150 microL/kg) value was much higher than its anticonvulsant doses (50-300 microL/kg). The results indicate that nutmeg oil may be effective against grand mal and partial seizures, as it prevents seizure spread in a set of established animal models. Slight potentiation of clonic seizure activity limits its use for the treatment of myoclonic and absence seizures.
There are two current approaches to the clinical conceptualization of the generalized epilepsies. The syndromic approach attempts to subdivide the patient population into relatively homogeneous groups, largely on the basis of clinical and EEG criteria. In contrast, the neurobiological approach aims to formulate a unique profile for each patient by incorporating particulars of the patient onto the background of knowledge regarding the etiologic factors important in generalized epilepsy. The value of these two approaches is discussed with regard to the dual aims of, first, improving the understanding of generalized epilepsy, and second, providing a precise diagnosis, an accurate prognosis, and optimal treatment for the patient.
gamma-Hydroxybutyrate (GHB) produces a constellation of EEG and behavioral events that respond selectively to antiabsence antiepileptic drugs. The GHB-induced seizure was quantitated in the presence of three other absence seizure models: pentylenetetrazole, systemic penicillin, and the flash evoked afterdischarge (FEAD). Penicillin and pentylenetetrazole produced a significant prolongation of GHB-induced seizure in a dose-dependent fashion. This potentiation of GHB seizure was observed when these compounds were given either before administration of gamma-butyrolactone (GBL), the prodrug of GHB, or at the onset of GHB-induced seizure. Photic stimulation given in a manner to produce FEAD also resulted in a significant prolongation of GHB-induced seizure. All of these maneuvers lowered the threshold to GHB seizure, but none interfered with the brain kinetics of GHB in the animals treated with GBL. Ethosuximide pretreatment significantly shortened the GHB seizure and overcame the potentiating effect of penicillin and pentylenetetrazole in this model. These data confirm the GHB-treated animal as a model of generalized absence seizure. The GHB model meets appropriate criteria for an absence seizure model and compares favorably with other models of absence currently in use.
The term “spike and wave” conveys the impression that the well known EEG pattern is composed of only two potentials and that it begins with the spike. This conception overlooks the fact that even in apparently simple complexes there are usually two negative spikes, a positive transient and a negative wave. The positive transient may be as significant as the other components since it is more closely related to the wave and since it is the only component which always seems to be present. Whatever is the actual mechanism for the generation of the spike-wave complex, its analysis is patients with petit mal epilepsy would suggest that it has morphological features in common with certain experimental evoked potentials.
The object of this study was to obtain information about the genetics of absence epilepsies from the family histories of patients and EEG examination of their siblings. There were 239 patients with absence epilepsy, and EEGs were recorded from 242 siblings of 109 patients, and 685 control children. In 30% of the families, at least one relative had a history of seizures. The highest incidence, 7% and 6%, was in siblings and parents. The incidence of seizures was higher in the families of female than of male probands. The EEGs of 242 siblings showed theta rhythms, spike wave patterns or photosensitivity in 28%. Of the siblings 1 to 8 yr old, 19% had theta rhythms, with a maximum incidence of 27% in children 3 to 4 yr old. This was significantly more frequent than in control children. Spike waves were elicited by photic stimulation in 12% of the siblings, with a maximum in children 11 to 12 yr old of 27%. Spike waves at rest and during hyperventilation were found in up to 20% of the siblings, depending on age. The maximum incidence in controls did not exceed 3%. Occipital delta rhythms showed a different age distribution in siblings and controls with a maximum at 9 to 10 yr in siblings and at 3 to 4 yr in controls. The overall incidence of occipital delta rhythms was about the same in siblings and controls. The relations of the various EEG traits with each other were analyzed. Theta rhythms, spike waves evoked by photic stimulation, and spike waves at rest and during hyperventilation occurred independently of each other in the siblings. Occipital delta activity and photosensitivity were inversely related, in that siblings of patients with delta rhythms were less often photosensitive than siblings of patients without delta activity. In accordance with former studies, occipital delta rhythms are interpreted as a symptom of a partially genetically determined inhibitory cerebral function. The relations between EEG findings in siblings and clinical data in the probands were examined. The only positive relation was that the siblings of patients with myoclonic astatic seizures had a significantly higher incidence of photosensitivity. Taken as a whole, the results suggest that epilepsies with spike wave absences are not inherited by an autosomal dominant gene, but that several genetic factors are responsible, some mutually independent and some either reinforcing or inhibiting the others.
In audiogenic seizure (AGS) susceptible rats, the acute (intraperitoneal and intravenous) dose-response effects of (--)-cannabidiol (CBD) for preventing AGS and for causing rototod neurotoxicity (ROT) were determined. Also, the anti-AGS and ROT effects of 10 CBD analogs, given in intravenous doses equivalent to the AGS-ED50 (15 mg/kg) and ROT-ID50 (31 mg/kg) of CBD, were ascertained. Compared to CBD, (--)-CBD diacetate and (--)-4-(2'-olivetyl)-alpha-pinene were equally effective whereas (--)-CBD monomethyl ether, (--)-CBD dimethyl ether, (--)-3'-acetyl-CBD monoacetate, (+)-4-(2'-olivetyl)-alpha-pinene, (--)-and (+)-4-(6'-olivetyl)-alpha-pinene, (+/-)-AF-11, and olivetol were less effective anticonvulsants. Except for (--)- and (+)-4-(2'-olivetyl)-alpha-pinene and olivetol, all analogs showed less ROT than CBD. Also, CBD and all analogs were not active in tetrahydrocannabinol seizure-susceptible rabbits, the latter a putative model of cannabinoid psychoactivity in humans. These data suggest anticonvulsant requirements of 2 free phenolic hydroxyl groups, exact positioning of the terpinoid moiety in the resorcinol system and correct stereochemistry. Moreover, findings of separation of anticonvulsant from neurotoxic and psychoactive activities, notably with CBD diacetate, suggest that additional structural modifications of CBD may yield novel antiepileptic drugs.
Primary Generalized Epilepsy (PGE) has been more hotly debated over the past decades than other forms of epileptic seizure disorder. The sudden synchronous appearance of bilateral spikes and spike-waves (mainly with myoclonus resp. absence) used to perplex the earliest generation of electroencephalographers, and the enigmatic genesis of these discharges (and seizures) has not ceased to fascinate the investigators of this phenomenon. A "centrencephalic" concept with paroxysmal discharges arising from thalamic structures and "projecting" to the cortex was championed for many years and eventually laid aside. More recently, the role of the thalamic level has been re-emphasized, mainly on the basis of experimental work. In this article, the bulk of experimental work is critically reviewed: the simian model (Papio papio), the feline, and the rodent models (Wistar rat, tottering mouse). Stress is being laid on fundamental differences between all of these models and human PGE. EEG evidence indicates a superior frontal origin of bilateral-synchronous spikes and spike-waves; depth EEG recordings in patients have failed to demonstrate primary thalamic spike generation. The heart of the matter in PGE appears to be the mechanism underlying paroxysmal discharges; above all the role of arousal. It is not awakening from sleep but the ensuing period that is critical in its epileptogenic thrust caused by alternating periods of return to drowsiness and arousing stimuli. This biphasic process gradually escalates EEG bursts to myoclonus (or absences) and possibly to a generalized tonic-clonic convulsion. Most conducive to this crescendo is the state of tiredness following a night of poor sleep. Bilateral synchrony is not precise and small time differences exist. The line between primary and secondary bilateral synchrony (with a primary cortical focus) can become blurred. Genetic predisposition to generalized paroxysms must always be considered, even in the face of a primary focus with secondary bilateral synchrony. Photosensitivity is a second paroxysm-inducing mechanism in PGE; it is much less common than the abnormal arousal ("dyshormia"); both mechanisms can be present in the same patient. Therapy and prevention of seizures in PGE are finally discussed. The concept of abnormal arousal mechanisms can be put into practice in order to prevent seizures: avoidance of sleepless nights, not always an easy task in adolescents and young adults.
In Wistar rats with spontaneous non-convulsive absence epilepsy, absence seizures were dose dependently suppressed by intraperitoneal administration of the GABAB receptor antagonists CGP 36742, 50-400 mg/kg, and CGP 56999, 0.25-0.75 mg/kg, and by bilateral microinjections of the same compounds into the lateral nuclei of the thalamus. In rats susceptible to audiogenic seizures, intraperitoneal administration of both GABAB receptor antagonists, at doses which suppressed absence seizures, facilitated the elicitation of sound-induced tonic seizures. In non-epileptic control rats, intraperitoneal injections of higher doses of CGP 36742 (800-2400 mg/kg) and CGP 56999 (3-6 mg/kg) induced delayed clonic convulsions, which were suppressed by pretreatment with baclofen. c-Fos protein was expressed after GABAB receptor antagonist-induced seizures in the cortex, hippocampus, amygdala, perirhinal and piriform cortex. Intra-cortical and hippocampal microinfusion of both GABAB receptor antagonists produced focal seizures. In conclusion, GABAB receptor antagonists suppress non-convulsive absence seizures by blocking thalamic GABAB receptors, while they induce convulsions in cortical and limbic structures.
The objectives of this study were to provide a comprehensive survey of satisfaction with care, care preferences and information provision for patients with epilepsy, and to formulate recommendations for the development of epilepsy services based on the findings. A questionnaire was distributed to 4620 patients who were currently receiving antiepileptic drugs for epilepsy, regardless of aetiology, duration or severity. Two different samples of patients with epilepsy were questioned: the first an unselected sample drawn from primary care, and the second consisting of consecutive patients drawn from hospital clinics. There were 2394 responses to the questionnaire. Satisfaction with primary and hospital care was high, both overall and for specific aspects. However, two major shortcomings were identified. First, few respondents felt that their care was shared between hospital and GP. Secondly, provision of information about epilepsy was perceived to be poor, particularly by the elderly. Younger patients and patients with severe epilepsy had a higher satisfaction with and preference for hospital care, whereas older age groups were more satisfied with and preferred primary care. Patients' main reasons for preferring primary care were that it was more personal and the GP was more familiar with them, and secondary care was preferred because the hospital doctor knew more about epilepsy. In conclusion, we have conducted the largest representative UK survey of patients' perceptions and views of the care available for epilepsy. Although patient satisfaction was high, information provision is poor and the shared care model is not operating effectively. We recommend that an emphasis be placed on methods for improving the interface between primary and secondary care. The setting up of hospital epilepsy centres, as recommended by the recently published Clinical Standards Advisory Group report on epilepsy, would provide a focus for these efforts and for information provision.
In humans with absence epilepsy, spike-and-wave discharges develop in the thalamocortical system during quiet immobile wakefulness or drowsiness. The present study examined the initial stage of the spontaneous development of spike-and-wave discharges in Genetic Absence Epilepsy Rats from Strasbourg. Bilateral electrocorticograms were recorded in epileptic and non-epileptic rats under freely moving and undrugged conditions and under neuroleptanalgesia. Short-lasting episodes of medium-voltage 5–9-Hz (mean=6-Hz) oscillations usually emerged spontaneously from a desynchronized electrocorticogram and in bilateral synchrony in both rat strains. These oscillations were distinguishable from sleep spindles regarding their internal frequency, duration, morphology, and moment of occurrence. Spontaneous spike-and-wave discharges developed from such synchronized medium-voltage oscillations, the spike-and-wave complex occurring at the same frequency as the 5–9-Hz wave.
We examined the difference between Escherichia coli O157 and non-pathogenic E. coli in their tolerance to spices. Various spices (5 g each) were homogenized at 25 degrees C for 10 min with 5 ml of 70% ethyl alcohol, and the supernatant solutions obtained by centrifugation were used as spice extracts. When the E. coli strains were incubated with each spice extract at concentrations of 0.01% and 0.1%, a noteworthy difference was observed between the O157 and non-pathogenic strains in their tolerance to nutmeg. The populations of the non-pathogenic strains could not be reduced, but those of the O157 strains were remarkably reduced. Antibacterial activity by the nutmeg extract was also found against the enteropathogenic E. coli O111, but not against enterotoxigenic (O6 and O148) and enteroinvasive (O29 and O124) E. coli. When we examined the antibacterial effect of volatile oils in nutmeg on the O157 and non-pathogenic E. coli strains, all O157 strains tested were found to be more sensitive to beta-pinene than non-pathogenic E. coli strains.
The present study was undertaken to investigate the effect of an n-hexane extract of Myristica fragrans seeds on depression in mice by using the forced swim test (FST) and the tail suspension test (TST). M. fragrans extract (5, 10, and 20 mg/kg) was administered orally for 3 successive days to different groups of Swiss male young albino mice. M. fragrans extract significantly decreased immobility periods of mice in both the FST and the TST. The 10 mg/kg dose was found to be most potent, as indicated by the greatest decrease in the immobility period compared with the control. Furthermore, this dose of the extract was found to have comparable potency to imipramine (15 mg/kg i.p.) and fluoxetine (20 mg/kg i.p.). The extract did not have a significant effect on locomotor activity of mice. Prazosin (62.5 microg/kg i.p.; an alpha (1)-adrenoceptor antagonist), sulpiride (50 mg/kg i.p.; a selective D(2) receptor antagonist), and p-chlorophenylalanine (100 mg/kg i.p.; an inhibitor of serotonin synthesis) significantly attenuated the M. fragrans extract-induced antidepressant-like effect in the TST. Thus, extract of M. fragrans elicited a significant antidepressant-like effect in mice, when assessed in both the TST and the FST. The antidepressant-like effect of the extract seems to be mediated by interaction with the adrenergic, dopaminergic, and serotonergic systems.
Paroxysmal 7- to 12-Hz high-voltage rhythmic spike (HVRS) or spike-wave discharges often appear in several particular strains of rats. However, functional hypotheses of these 7-12 Hz high-voltage cortical oscillations (absence seizure vs. idling mu rhythm) are inconclusive. The mu rhythm can be provoked by flicker stimulation (FS) in most people, but FS is less effective at eliciting absence epileptic activity. Therefore FS and antiepileptic drugs were used to verify the role of HVRS activity in Long-Evans rats with spontaneous HVRS discharges and Wistar rats without spontaneous HVRS discharges. The occurrence of HVRS discharges was significantly reduced by antiabsence drugs (ethosuximide, valproic acid, and diazepam) in dose-dependent manners, but high-dose carbamazepine displayed little effect. On the other hand, oscillation frequencies and durations of spontaneous HVRS discharges were not altered by FS. Under asynchronous brain activity, many FSs (>60%) elicited small-amplitude mu-rhythm-like activity in the barrel cortex concomitant with FS-related rhythms in the occipital cortex and resulted in significant augmentation of 7-12 Hz power in the parietal region. Furthermore, a large portion of FSs (>60%) revealed increase of 7-12 Hz power of the parietal cortex after ethosuximide administration (100 mg/kg ip) in Long-Evans rats. Similar FS-elicited phenomena also appeared in Wistar rats. Characteristics of FS-elicited mu-rhythm-like activities were consistent with those observed in humans, and they remarkably differed from those of spontaneous HVRS discharges. These results support the hypothesis that HVRS activity in Long-Evans rats may be an absence-like seizure activity rather than the mu rhythm.
Time-frequency dynamics of spike-wave discharges (SWDs) were investigated in patients with absence seizures and in WAG/Rij rats, a genetic model of absence epilepsy using a specially developed wavelet transform. Two types of SWDs were analyzed in both species: the most frequently occurring discharges (of minimal 3.6-4.0 s or more) and shorter ones recorded from various cortical regions. The more prolonged discharges had two phases: during the initial part (from tenth of seconds to 1 s) of the seizure the frequency decreased quickly from 5 to 3.5 Hz in patients and from about 15 to 10 Hz in rats. A slower frequency decrease with periodical fluctuations was observed in both species during the second part of the discharge: the frequency decreased towards the end of the discharge to 3 Hz in patients and to 6-7 Hz in rats. The frequency of the short discharges decreased fast during the whole discharge: from 5 to 2-2.5 Hz and from about 15 to 5 Hz in patients and rats, respectively. Comparison of data obtained in patients with typical absence epilepsy and WAG/Rij rats with genetic absence epilepsy revealed that the time-frequency dynamics of SWDs had similar properties but in a different frequency range. The study of time-frequency dynamics using this specially developed wavelet transform revealed two different types of SWDs, which most likely represent different dynamics in the cortico-thalamo-cortical loop during shorter and more prolonged discharges.
Typical absence seizures and related epileptic syndromes: assessment of current state and directions for future research
  • C P Panayiotopoulos
Panayiotopoulos CP. Typical absence seizures and related epileptic syndromes: assessment of current state and directions for future research. Epilepsia. 2008;49(12):2131-2139. doi: 10.1111/j.1528-1167. 2008.01777.
Pathophysiological mechanisms of genetic absence epilepsy in the rat
  • L Danober
  • C Deransart
  • A Depaulis
  • M Vergnes
  • C Marescaux
Danober L, Deransart C, Depaulis A, Vergnes M, Marescaux C. Pathophysiological mechanisms of genetic absence epilepsy in the rat. Prog Neurobiol. 1998;55(1):27-57. doi: 10.1016/S0301-0082(97)00091-9.
Detection of SWD in the cortical EEG of GAERS
  • P Van Hese
  • J P Marten
  • S Dedeurwaerdere
  • P Boon
  • Lamahieu
Van Hese P, Marten JP, Dedeurwaerdere S, Boon P, Lamahieu et al. Detection of SWD in the cortical EEG of GAERS. Phys Med Biol. 2003;48(12):1685-1700. doi:10.1088/0031-9155/48/12/302.
The spectrum of anticovulsant efficacy of retibine (ezogabine) in animal models: Implications for clinical use
  • C H Large
  • D M Sokal
  • A Nehlig
  • M J Gunthorpe
  • R Sankar
  • C S Crean
Large CH, Sokal DM, Nehlig A, Gunthorpe MJ, Sankar R, Crean CS, et al. The spectrum of anticovulsant efficacy of retibine (ezogabine) in animal models: Implications for clinical use. Epilepsia. 2012;53(3):425-436. doi: 10.1111/j.15281167.2011.03364.x.
EEG spike activity precedes epilepsy after kainite-induced status epilepticus
  • A White
  • P A Williams
  • J L Hellier
  • S Clark
  • F E Dudek
  • K J Staley
White A, Williams PA, Hellier JL, Clark S, Dudek FE, Staley KJ. EEG spike activity precedes epilepsy after kainite-induced status epilepticus. Epilepsia. 2010;51(3):371-383. doi: 10.1111/j.1528-1167.2009.02339.
Electrophysiological and pharmacological characteristics of two types of spike-wave discharges in WAG/Rij rats
  • I S Midzianovskaia
  • G D Kuznetsova
  • A M Coenen
  • A M Spiridonov
  • E L Van Luijtelaar
Midzianovskaia IS, Kuznetsova GD, Coenen AM, Spiridonov AM, van Luijtelaar EL. Electrophysiological and pharmacological characteristics of two types of spike-wave discharges in WAG/Rij rats. Brain Res. 2001;911(1):62-70. doi: 10.1016/S0006-8993 (01)02705-6.
Electroencephalographic characterization of spike-wave discharges in cortex and thalamus in WAG/Rij rats
  • E Sitnikova
  • G Van Luijtelaar
Sitnikova E, van Luijtelaar G. Electroencephalographic characterization of spike-wave discharges in cortex and thalamus in WAG/Rij rats. Epilepsia. 2007;48(12):2296-2311. doi: 10.1111/j.1528-1167. 2007.01250.
In: Epilepsy and related disorders
  • W G Lennox
  • M A Lennox
Lennox WG, Lennox MA. In: Epilepsy and related disorders. Volume 1&2. Boston (MA): Little Brown & Co;1960.
Pathophysiological mechanisms of experimental generalized absence seizures in rats
  • O C Snead
  • A Malafosse
  • P Genton
  • E Hirsch
  • C Marescaux
  • D Broglin
  • R Bernasconi
Snead OC. Pathophysiological mechanisms of experimental generalized absence seizures in rats. In: Malafosse A, Genton P, Hirsch E, Marescaux C, Broglin D, Bernasconi R, editors. Idiopathic Generalized Epilepsies: Clinic Exp Genetic Aspects. London (LN): John Libbey; 1994. p. 133-150.