Epileptic seizures induce structural and functional alterations on brain tissue membranes.

Epilepsy is characterized by disruption of balance between cerebral excitation and inhibition, leading to recurrent and unprovoked convulsions. Studies are still underway to understand mechanisms lying epileptic seizures with the aim of improving treatment strategies. In this context, the research on brain tissue membranes gains importance for generation of epileptic activities. In order to provide additional information for this field, we have investigated the effects of pentylenetetrazol-induced and audiogenetically susceptible epileptic seizures on structure, content and function of rat brain membrane components using Fourier transform infrared (FT-IR) spectroscopy. The findings have shown that both two types of epileptic seizures stimulate the variations in the molecular organization of membrane lipids, which have potential to influence the structures in connection with functions of membrane proteins. Moreover, less fluid lipid structure and a decline in content of lipids obtained from the ratio of CH3 asym/lipid, CH2 asym/lipid, CO/lipid, and olefinicCH/lipid and the areas of the PO2 symmetric and asymmetric modes were observed. Moreover, based on IR data the changes in the conformation of proteins were predicted by neural network (NN) analysis, and displayed as an increase in random coil despite a decrease in beta sheet. Depending on spectral parameters, we have successfully differentiated treated samples from the control by principal component analysis (PCA) and cluster analysis. In summary, FT-IR spectroscopy may offer promising attempt to identify compositional, structural and functional alterations in brain tissue membranes resulting from epileptic activities.

Investigation of compositional, structural, and dynamical changes of pentylenetetrazol-induced seizures on a rat brain by FT-IR spectroscopy.

To accomplish the appropriate treatment strategies of epilepsy action mechanisms underlying epileptic seizures should be lightened. The identification of epileptic seizure-induced alterations on the brain related to their pathologies may provide information for its action mechanism. Therefore, the current study determined molecular consequences of seizures induced by pentylenetetrazol (PTZ), which is a widely used convulsant agent, on rat brain. The rats were administered subconvulsant (25 mg/kg) and convulsant (60 mg/kg) doses of PTZ during a week, and brain tissues were studied by Fourier transform infrared (FT-IR) spectroscopy. Results revealed a decrease in lipid fluidity and lipid and protein content and also the differences in membrane packing by changing the nature of hydrogen bonding as indicated by the C═O, the PO(-)2 symmetric, and asymmetric bands. Monitoring of the olefinic band elicited seizure-induced lipid peroxidation further confirmed by the thiobarbituric acid (TBAR) assay. Additionally, PTZ-induced convulsions led to alterations in protein structures obtained by neural network (NN) predictions like an increase in random coils. On the basis of the spectral changes, treated samples could be successfully differentiated from the controls by cluster analysis. Consequently, the convulsive dose of PTZ caused more significant molecular variations compared to the subconvulsive one. All findings might have an important role in understanding the molecular mechanisms underlying epileptic activities.

Convulsant agent pentylenetetrazol does not alter the structural and dynamical properties of dipalmitoylphosphatidylcholine model membranes.

Pentylenetetrazol (PTZ) is an epileptogenic agent, which is widely used in the determination of epilepsy-induced alterations and in the assessment of anticonvulsant agents in epileptic studies. Even though PTZ is suggested to induce repetitive firing of nerve fibers and shorten the refractory, its mechanism of action is only partially understood. In the literature there are discrepancies for its action mechanism. While some studies stated that primary sites of PTZ are membrane proteins, some reports indicated that PTZ acts on membrane lipids. In order to gain new insight for this we tested the possibility of interaction of PTZ with a simplified model system called dipalmitoylphosphatidylcholine (DPPC) multilamellar vesicles (MLVs) at agent concentrations (0-24 mol%) using differential scanning calorimetry (DSC), Fourier transform infrared (FTIR), electron spin resonance (ESR) and steady-state fluorescence spectroscopy. The results showed that PTZ at concentrations used (1-24 mol%), does not cause any significant change in lipid phase behavior, lipid dynamics (fluidity), lipid acyl chain flexibility (order), hydration state of the head group and/or the region near the head group of DPPC MLVs. These results clearly revealed that PTZ does not change the structural and dynamical parameters of neutral DPPC lipid vesicles and does not locate within the bilayer.