Abstract
Kindling, one of the most used models of experimental epilepsy is based on daily electrical stimulation in several brain structures. Unlike the classic or slow kindling protocols (SK), the rapid kindling types (RK) described until now require continuous stimulation at suprathreshold intensities applied directly to the same brain structure used for subsequent electrophysiological and immunohistochemical studies, usually the hippocampus. However, the cellular changes observed in these rapid protocols, such as astrogliosis and neuronal loss, could be due to experimental manipulation more than to epileptogenesis-related alterations. Here, we developed a new RK protocol in order to generate an improved model of temporal lobe epilepsy (TLE) which allows gradual progression of the epilepsy as well as obtaining an epileptic hippocampus, thus avoiding direct surgical manipulation and electric stimulation over this structure. This new protocol consists of basolateral amygdala (BLA) stimulation with 10 trains of biphasic pulses (10 s; 50 Hz) per day with 20 min-intervals, during 3 consecutive days, using a subconvulsive and subthreshold intensity, which guarantees tissue integrity. The progression of epileptic activity was evaluated in freely moving rats through electroencephalographic (EEG) recordings from cortex and amygdala, accompanied with synchronized video recordings. Moreover, we assessed the effectiveness of RK protocol and the establishment of epilepsy by evaluating cellular alterations of hippocampal slices from kindled rats. RK protocol induced convulsive states similar to SK protocols but in 3 days, with persistently lowered threshold to seizure induction and epileptogenic-dependent cellular changes in amygdala projection areas. We concluded that this novel RK protocol introduces a new variant of the chronic epileptogenesis models in freely moving rats, which is faster, highly reproducible and causes minimum cell damage with respect to that observed in other experimental models of epilepsy.
Highlights
Epilepsy encloses a set of neurological disorders of diverse etiology, characterized by the development of gradual and progressive spontaneous seizures, which increase in recurrence and severity with time
CHANGES IN EEG RECORDINGS FROM basolateral amygdala (BLA) AND M1 INDUCED BY slow kindling protocols (SK) AND rapid kindling types (RK) PROTOCOLS In order to compare the progression of epileptiform activity induced by our RK variant with regards to traditional SK protocols, we assessed the electrical activity evoked in the BLA
Our RK protocol provides a reproducible method for fast induction of experimental epileptogenesis in adult rats while keeping the subthreshold stimulation and gradual progression of epileptic activity of SK protocols
Summary
Epilepsy encloses a set of neurological disorders of diverse etiology, characterized by the development of gradual and progressive spontaneous seizures, which increase in recurrence and severity with time. Most of the in vivo experimental epilepsy models have been based on pharmacological manipulations (i.e., chemical-kindling) (Dhir, 2012) or electrical stimulation (Morimoto et al, 2004; McNamara et al, 2006). Kindling remains one of the few chronic models available to study epilepsy development (i.e., epileptogenesis) (Goddard, 1967, 1983; Goddard et al, 1969; Racine, 1972b; Lothman et al, 1985). The conventional kindling protocol consists of repetitive subconvulsive electrical stimulation that elicits gradual and progressive enhancement of electroencephalographic (EEG) activity and behavioral responses, culminating in generalized seizures (Goddard et al, 1969; Racine, 1972b). The protocol progression is assessed through a behavioral scale known as “Racine Stages” (Racine, 1972b), which can be directly correlated with the AD duration and EEG
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