Advanced understanding in mechanisms of epilepsy and potential new treatment strategies

Over the last 25 years, neurobiologists have begun to unravel the cellular mechanisms that underlie epileptiform activity. Such investigations have two main objectives: [1] to develop new methods for treating, [curing], or preventing epilepsy; and [2] to learn more about the normal functioning of the human brain, at the cellular/molecular and neurological/psychological levels by analyzing abnormal brain functioning. The electroencephalogram [EF.G] spike is a marker for the hyperexcitable cortex and arises in or near an area with a high epileptogenic potential. The depolarizing shift [DS] that underlies the interictal discharge [ID] appears to be generated by a combination of excitatory synaptic currents and intrinsic voltage-dependent membrane currents. The hyperpolarization that follows the DS [post-DS-1 IT] hunts ID duration, determines ID frequency, and prevents ID deterioration into seizures. The disappearance of the post-DS I IP in some models is related to the onset of seizures and the spread of epileptiform activity. During the transition to seizures, the usually self-limited ID spreads in time and anatomical space. Several processes may intervene in the pathophysiolpgical dysfunction. These include enhancing GABA-mediated inhibition, dampening NMDA-mediated excitability, interfering with specific Ca[2+] currents in central neurons, and perhaps stimulating [gating] pathways

Analgesic and anticonvulsant effects of extracts from the leaves of strychnos nux vomica Linn.

Strychnos nux vomica belongs to family Loganiaceae, is a fleshy herbaceous plant used in the Indian traditional medicine as remedy against nervine disorders with stomachic tonic, aphrodisiac, spinal stimulant, respiratory and cardiac stimulant activities. In excessive doses, it is a virulent poison producing tetanic convulsions. In the present work, the analgesic effects of methylene chloride/methanol [1:1] [CH2CI2/CH3OH] extract and its hexane, methylene chloride [CH2CI2], ethyl acetate, n-butanol fractions and aqueous residue have been evaluated using acetic acid, formalin and pressure test. The anticonvulsant effects of CH2CI2/CH3OH extract were also investigated on seizures induced by pentylene tetrazol [PTZ 70 mg/kg], strychnine sulphate [STN 2.5 mg/kg] and thiosemicarbazide [TSC 50 mg/kg]. CH2CI2/CH3OH extract and its fractions, administered orally at the doses of 150 and 300 mg/kg, exhibited protective effect of at least 30% on the pain induced by acetic acid. The CH2CI2 fraction at 300 mg/kg showed a maximal effect of 78.49%. The CH2CI2/CH3OH extract and its CH2CI2 fraction at the doses of 150 and 300 mg/kg significantly reduced the first phase of pain induced by formalin while the second phase was completely inhibited. The CH2CI2 fraction produced more than 45% reduction in the sensitivity to pain induced by pressure. The CH2CI2/CH3OH extract of Strychnos nux vomica significantly increased the latency period in seizures induced by PTZ and significantly reduced the duration of seizures induced by the three convulsant agents. The extract protected 20% of animals death in seizures induced by TSC and STN. These results suggest peripheral and central analgesic activities as well as an anticonvulsant effect of the leaves of Strychnos nux vomica

Anticonvulsant activity of Alangium salvifolium stem bark

The anticonvulsant activity of methanolic extract of Alangium salvifolium stem barks in doses 100, 200, 400, 500 mg/kg in mice was assessed using maximum electroshock seizure [MES] test and pentylenetetrazol [PTZ]-induced convulsion in albino mice. The lithium pilocarpine model of status epilepticus was also used to assess the anti-convulsant activity in rats. The methanolic extract of Alangium salvifolium stem bark did not reduce the duration of tonic hindleg extention in the MES test even in the dose of 500 mg/kg. However, this extract significantly and dose dependently delayed the onset of clonis convulsions induced by pentyletetrazol. The dose of 100 mg/kg afforded protection to all animals. The methanolic extract of Alangium salvifolium stem bark inhibited the PTZ and lithium pilocarpine-induced convulsions but MES induced convulsions condition remained unchanged