Pharmacologically induced absence seizures versus kindling in Wistar rats.

OBJECTIVE: This study aimed to investigate the effects of γ-butyrolactone (GBL), a prodrug of gamma-Hydroxybutyric acid -induced absence seizures on the development of kindling in Wistar rats. METHODS: Three groups of adult male Wistar rats under anesthesia were implanted with bilateral cortical recording electrodes for the GBL group (GBL) and/or bipolar stimulation electrodes into the right basolateral amygdala for the Kindling group (KI) alone and Kindling plus GBL group (GBL+KI). Rats in the KI and GBL+KI groups were stimulated twice daily at the afterdischarge threshold until they reached Racine's stage 5 seizure state. The animals in the GBL + group had an i.p injection of GBL 20 minutes before each electrical stimulation, and the effects of GBL-induced seizures on the development of kindling were investigated. The animals in the GBL group were injected GBL twice daily i.p. for 15 days without receiving any electrical stimulation. RESULTS: The KI animals reached stage 5 seizure stage at 12th stimulations, whereas the GBL+KI rats reached at 27th stimulations. The mean numbers of stimulations needed for the development of the first stage 3, 4, or 5 generalized seizures were significantly higher in the GBL+KI group than the KI group. CONCLUSION: The resistance to amygdala kindling in the GBL model can be modulated by the absence seizure mechanism alone, without the intervention of an abnormal genetic background.

[THE NASCENCY OF DRUG AND FIRST STEPS OF ITS DEVELOPMENT].

In this historical review article, the first examples of human attempts to use drugs for the solution of their health problems and the development of the concept of natural toxic (poisonous) substances in the history and prehistoric times, are discussed. It is regarded that, outside of the quelling of the hunger or quenching the thirst, some of our early an- cestors have coincidentally began to distinguish the different effects in some of the natural products in their environment, probably during their nutritional behavior. It is thought that in this way, the awareness for drugs and toxic substances have been raised. In our available sources related to this topic, the first instance in different societies that can be considered as drug seems to belong to different dates, and strikingly the earliest drug samples were found particularly in ancient Mesopotamia, Egypt, China and Indian civilizations. It was determined that primarily herbal resources were utilized for the first instance that can be considered as the first drug application in discussed societies. On the other hand, these first natural origin drug samples have been remained in the use of humankind in later centuries and some of them seems to be applied in a certain manner even today.

Resistance to propagation of amygdaloid kindling seizures in rats with genetic absence epilepsy.

PURPOSE: The existence of absence epilepsy and temporal partial seizure pattern in the same patient is an uncommon state. In the present study, we aimed to evaluate whether the process of kindling as a model of complex partial seizures with secondary generalization is altered in rats with genetic absence epilepsy. METHODS: Six- to 12-month-old nonepileptic control Wistar rats and genetic absence epileptic rats from Strasbourg (GAERS) were used in the experiments. One week before the experiments, bilateral stimulation and recording electrodes were implanted stereotaxically into the basolateral amygdala and cortex, respectively. Animals were stimulated at their afterdischarge threshold current twice daily for the process of kindling and accepted as fully kindled after the occurrence of five grade 5 seizures. Bilateral EEGs from amygdala and cortex were recorded continuously during 20 min before and 40 min after each stimulus. RESULTS: All control Wistar rats were fully kindled after stimulus 12 to 15. Although the maximal number of stimulations had been applied, GAERS remained at stage 2, and no motor seizures were observed. The afterdischarge duration in bilateral amygdala and the cortex after the kindling stimulus was shorter in GAERS when compared with control rats. CONCLUSIONS: Occurrence of only grade 2 seizures and no observation of grade 3-5 seizures in GAERS with the maximal number of stimulations would suggest that the generalized absence seizures may be the reason of the resistance in the secondary generalization of limbic seizures during amygdala kindling.

An association between mesial temporal lobe epilepsy with hippocampal sclerosis and human leukocyte antigens.

PURPOSE: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is one of the medically intractable epilepsies that may be remediable with surgery. Although the pathogenesis of HS still remains obscure, genetics may play a role as a predisposing factor, with the genetically controlled immune system as one of its aspects. Our aim in this study was to investigate whether there is any association between human leukocyte antigens (HLAs) that are related to chromosome 6 and this specific type of epilepsy. METHODS: HLA class I and II typing were performed with the microlymphocytotoxicity method on 65 Turkish patients with MTLE-HS and on 184 healthy controls. RESULTS: Our study revealed a significantly high frequency of class II antigens HLA-DQ2, -DR4, and -DR7 alleles and the combination of HLA-DR4-DQ2, and DR7-DQ2 alleles. CONCLUSIONS: The HLA alleles that occur with increased frequency in many HLA- associated conditions appear to serve as risk factors that increase susceptibility but are not essential for disease expression. Our data support the role of genetic factors in the development of HS, possibly related to early childhood events that may act as a trigger factor to initiate the cascade in genetically prone patients with specific HLA types to give rise to MTLE eventually.