ABSTRACT
Epilepsy clinically has an inhibitory impact on cognitive function, but whether it is associated with epileptogenesis is unclear. Since the epileptic spike characterizes temporal lobe epilepsy (TLE), the present study was aimed to analyze the transient effects of sporadic spikes (SSs) on theta rhythm during epileptogenesis. The local field potentials (LFPs) were recorded in CA1 area in four rats with the pilocarpine injections during exploration, and theta phase stability and power were globally estimated around SSs, also during prolonged period without SS (both as experiments) as well as pre-injections (control). Finally, the LFPs were simulated by changing the average excitatory and inhibitory synaptic gain values (including slow and fast inhibition loops) with the help of simplified dynamical model of CA1 networks, and then theta phase stability was evaluated in several cases. It was found that the SSs could have negative impacts on theta rhythm both transiently and persistently, which may be dependent on the temporal courses leading to epilepsy, being acuter in early stage than later stage, but even in latent stage, theta power was strong. The simulations partly demonstrated that the synaptic imbalance concomitant with the occurrence of SSs might be related to the dynamics of theta phase stability. The results indicate that the SSs might have persistent negative impacts on the cognition rhythm, and the effects might alter during epileptogenesis, leading to the cognitive dysfunction.
Subject(s)
Animals , Rats , CA1 Region, Hippocampal , Epilepsy, Temporal Lobe , Pilocarpine , Theta RhythmABSTRACT
<p><b>OBJECTIVE</b>To study the cardiovascular effect of selective orexin-1 receptor (OX1R) antagonist SB408124 in anesthetized rats and explore the underlying mechanism by using intracerebroventricular (ICV) microinjection combined with immunohistochemical assay.</p><p><b>METHODS</b>The changes of mean arterial blood pressure (MAP) and heart rate (HR) of male Sprague-Dawley rats were recorded during ICV microinjection of SB408124 with or without pretreatment of atropine methyl nitrate or hexamethonium bromide. Furthermore, tyrosine hydroxylase (TH) immunopositive neurons in the rostral ventrolateral medulla (RVLM) of the rat were detected with immunohistochemical assay after ICV microinjection of SB408124.</p><p><b>RESULTS</b>ICV administration of SB408124 resulted in a significant decrease in MAP in anesthetized rats, which was accompanied with a mild decrease in HR. The cardiovascular responses elicited by SB408124 were not abolished by pretreatment of atropine methyl nitrate whereas fully abolished by pretreatment of hexamethonium bromide. The number of TH-immunopositive neurons in rat RVLM were significantly decreased following ICV administration of SB408124.</p><p><b>CONCLUSION</b>ICV microinjection of selective OX1R antagonist SB408124 can cause decreases of MAP and HR mediated by inhibiting sympathetic activity in anesthetized rats.</p>