RESUMO
Low frequency stimulation (LFS) has an inhibitory effect on rapid perforant path kindling acquisition. In the present study the role of adenosine A(1) and A(2A) receptors in mediating this inhibitory effect was investigated. Rats were kindled by perforant path stimulation using rapid kindling procedures (12 stimulations per day). LFS (0.1 ms pulse duration at 1 Hz, 200 pulses, and 50-150 muA) was applied to the perforant path immediately after termination of each rapid kindling stimulation. 1,3-Dimethyl-8-cyclopenthylxanthine (CPT; 50 muM), a selective A(1) antagonist and ZM241385 (ZM, 200 muM), a selective A(2A) antagonist were daily microinjected into the lateral ventricle 5 min before kindling stimulations. LFS had an inhibitory effect on kindling development. Pretreatment of animals with CPT reduced the inhibitory effect of LFS on kindling rate and suppressed the effects of LFS on potentiation of population EPSP during kindling acquisition. In addition, CPT was able to antagonize the effects of LFS on kindling-induced increase in early (10-50 ms intervals) and late (300-1000 ms intervals) paired pulse depression. ZM pretreatment had no effect on antiepileptogenic effects of LFS in kindling acquisition. In addition, LFS prevented the kindling-induced elevation of cyclic AMP (cAMP) levels in kindled animals. Based on these results, we suggest that the antiepileptogenic effects of LFS on perforant path kindling might be mediated through activation of adenosine A(1), but not A(2A) receptors. Moreover, modulation of cAMP levels by LFS may potentially be an important mechanism which explains the anticonvulsant effects of LFS in kindled seizures.
Assuntos
Excitação Neurológica/fisiologia , Inibição Neural/fisiologia , Via Perfurante/metabolismo , Receptor A1 de Adenosina/fisiologia , Antagonistas do Receptor A1 de Adenosina , Antagonistas do Receptor A2 de Adenosina , Análise de Variância , Animais , Biofísica , AMP Cíclico/metabolismo , Estimulação Elétrica/métodos , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Excitação Neurológica/efeitos dos fármacos , Masculino , Inibição Neural/efeitos dos fármacos , Via Perfurante/efeitos dos fármacos , Ratos , Ratos Wistar , Convulsões/metabolismo , Convulsões/fisiopatologia , Fatores de Tempo , Triazinas , Triazóis , Xantinas/farmacologiaRESUMO
Low-frequency stimulation (LFS) has antiepileptogenic effects on kindled seizures. In the present study, the role of galanin receptors in the inhibitory effect of LFS on perforant path kindling acquisition was investigated in rats. Animals were kindled by perforant path stimulation in a rapid kindling manner (six stimulations per day). LFS (0.1 ms pulses at 1 Hz, 600 pulses, and 80-150 microA) was applied immediately after termination of each kindling stimulation. M35 (0.5 and 1.0 nM per site), a nonselective galanin receptor antagonist and M871 (1.0 microM per site), a selective galanin receptor type 2 (GalR2) antagonist, were daily microinjected into the dentate gyrus before starting the stimulation protocol. The expression of GalR2 in the dentate gyrus was also investigated using semi-quantitative RT-PCR. Application of LFS significantly retarded the kindling acquisition and delayed the expression of different kindled seizure stages. In addition, LFS significantly reduced the increment of daily afterdischarge duration during kindling development. Intra-dentate gyrus microinjection of both M35 and M871 significantly prevented the inhibitory effects of LFS on kindling parameters. During the focal kindled seizure stages (1-3) M871 had no significant effect. However, during generalized seizure stages (4 and 5), M871 had the same effect as M35. Semi-quantitative RT-PCR also showed that after kindling acquisition, the GalR2 mRNA level decreased in the dentate gyrus but application of LFS prevented this decrease. Obtained results show that activation of galanin receptors by endogenous galanin has a role in mediating the inhibitory effect of LFS on perforant path-kindled seizures. This role is exerted through GalR1 during focal- and through GalR2 during generalized-kindled seizures.
Assuntos
Epilepsia/metabolismo , Hipocampo/metabolismo , Excitação Neurológica/metabolismo , Via Perfurante/metabolismo , Receptores de Galanina/metabolismo , Convulsões/metabolismo , Animais , Modelos Animais de Doenças , Terapia por Estimulação Elétrica , Epilepsia/fisiopatologia , Epilepsia/terapia , Galanina/metabolismo , Hipocampo/fisiopatologia , Excitação Neurológica/efeitos dos fármacos , Masculino , Microinjeções , Via Perfurante/fisiopatologia , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptor Tipo 1 de Galanina/antagonistas & inibidores , Receptor Tipo 1 de Galanina/genética , Receptor Tipo 1 de Galanina/metabolismo , Receptor Tipo 2 de Galanina/antagonistas & inibidores , Receptor Tipo 2 de Galanina/genética , Receptor Tipo 2 de Galanina/metabolismo , Receptores de Galanina/antagonistas & inibidores , Receptores de Galanina/genética , Convulsões/fisiopatologia , Convulsões/terapia , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologiaRESUMO
Key challenges for design of intravascular loop probes are minimization of the cross sectional and length while increasing signal-to-noise ratio (SNR). Although NPO grade captors under 1mm dimensions are now available, the impedance matching network components still constrain tunability. In this study, a new loop probe is proposed for intravascular magnetic resonance imaging (MRI) at 1.5 Tesla. The new design is based on a two-turn loop, separated by a gap, which can be placed over a perfused inflatable balloon structure. The length and impedance of the probe are 1.1 cm and 23.5OHM (bare case), respectively. The SNR of the new probe is greater than the conventional loop probe. To evaluate the performance of the probe, a series of SNR, length, and impedance comparisons with the conventional loop probes are carried out.