ABSTRACT
Brain damage and neuronal loss caused by traumatic brain injury, ischemic stroke, and symptomatic status epilepticus can lead to severe long-term consequences, such as impairment in learning and memory and cognitive functions, and development of chronic epilepsy. This can be the result of morphologic and functional changes underlying temporal lobe epilepsy. Epilepsy patients have increased risk of status epilepticus. It is a life-threatening condition when seizures last for more than 30 min and trigger processes leading to neuronal apoptosis and necrosis in various parts of brain. Administration of neuroprotective drugs preventing these pathologic processes could improve the prognosis for such patients. However despite of active research of neuroprotective drugs, the effective ways to prevent brain damage resulting from prolonged seizures are yet to be found. Studies of neuroprotective properties of classic and novel anticonvulsant drugs showed that most of them do not have the sufficient neuroprotective effect and are not able to prevent epileptogenesis. Thus the studies of other potential neuroprotective drugs seem to be promising.
Subject(s)
Brain Injuries/complications , Cell Death/physiology , Epilepsy, Post-Traumatic/physiopathology , Epilepsy, Temporal Lobe/drug therapy , Neurons/pathology , Neuroprotective Agents/therapeutic use , Animals , Anticonvulsants/therapeutic use , Brain/diagnostic imaging , Brain/physiopathology , Drugs, Chinese Herbal/therapeutic use , Epilepsy, Post-Traumatic/drug therapy , Epilepsy, Post-Traumatic/etiology , Epilepsy, Temporal Lobe/etiology , Epilepsy, Temporal Lobe/physiopathology , Humans , Neurons/physiology , Neuropeptides/therapeutic use , Panax/chemistry , Radiography , RatsABSTRACT
The origin of generalized absence epilepsy is still not known. In the last century, four theories have dominated the debate about the origin of the bilateral synchronous generalized spike-wave discharges associated with absence seizures: the "centrencephalic" theory [Penfield and Jasper], the "cortical" [Bancaud, Niedermeyer, Luders], the "cortico-reticular" theory [Gloor, Kostop[oulos, Avoli] and the "thalamic clock" theory [Buzsaki]. There is now some evidence that absence epilepsy, as studied in the WAG/Rij model, is a corticothalamic type of epilepsy. A new hypothesis is proposed which suggests that a cortical focus in the somatosensory cortex is driving the widespread corticothalamic networks during spontaneous absence seizures. This modern theory was given the name "hot spot' theory" [Meeren et al., 2002]. According to the present view three brain structures are critically involved and their integrity seems a minimal and sufficient condition for the occurrence of spike-wave discharges. Firstly, the reticular thalamic nucleus is involved and most likely its rostral pole. Secondly, the thalamocortical relay cells in the ventrobasal complex play a role and, thirdly and most importantly, the cerebral cortex with its epileptic zone. The zone in which the epileptic focus seems to be localised is located on the somato-sensory cortex, and more precisely in the area on which the peri-oral region including the upper lip, projects.
Subject(s)
Cerebral Cortex/physiopathology , Epilepsy, Absence/physiopathology , Thalamus/physiopathology , Animals , Brain/physiopathology , Disease Models, Animal , Humans , Intralaminar Thalamic Nuclei/physiopathology , RatsABSTRACT
Frontoparietal cortex and the thalamocortical circuit comprising reticular thalamic nucleus (RTN) and relay nuclei of the ventrolateral thalamus (VLT) are critical structures in the generation of spike-wave discharges (SWD) during absence seizures. The activity of these nuclei is under the control of the ascending cholinergic projections of nucleus basalis of Meynert. The aim of our study is to make an attempt to change the pattern of SWD in WAG/Rij rats by injecting of cholinotoxine AF64A to the area of RTN. Spontaneous SWD were registered in cortex of WAG/Rij rats with genetically determined absences. The spectral content of SWD was analyzed by means of the Fast Fourier Transformation (FFT) procedure. Unilateral injections of AF64A (1 nmol) to RTN led the decrease in duration and number of SWD comparing to the basal EEG recordings 2 days after the lesion. The FFT analysis showed the disappearance of 17-18 Hz spike on the side of the lesion compared with the intact side. The immunohistochemical study for acetylcholinetransferase (ChaT)-containing neurons showed the loss of ChaT-positive cells in the nucleus basalis area on the side of the lesion. The removal of cholinergic afferentation of RTN and cortex from nucleus basalis inhibits the SWD developing most likely due to the decrease of cortical excitability. Moreover, possibly cholinergic transmission is involved in the transforation of the synchronized phenomena (SWD) to another with close mechanism of generation.
Subject(s)
Choline/analogs & derivatives , Epilepsy, Absence/physiopathology , Receptors, Cholinergic/physiology , Animals , Aziridines/toxicity , Brain/physiopathology , Choline/toxicity , Epilepsy, Absence/genetics , Galanin/physiology , Humans , Rats , Receptors, Cholinergic/drug effects , Thalamus/physiopathologySubject(s)
Avoidance Learning/drug effects , Escape Reaction/drug effects , Memory/drug effects , Panax/chemistry , Plants, Medicinal , Polysaccharides/pharmacology , Animals , Conditioning, Classical/drug effects , Conditioning, Classical/physiology , Escape Reaction/physiology , Male , Memory/physiology , Plant Extracts/pharmacology , Rats , Rats, Wistar , Reaction Time/drug effectsSubject(s)
Aversive Therapy , Maze Learning/physiology , Panax , Plants, Medicinal , Reinforcement, Psychology , Saponins/pharmacology , Smell , Animals , Dizocilpine Maleate/pharmacology , Drinking , GABA Antagonists/pharmacology , Ginsenosides , Maze Learning/drug effects , Mice , Mice, Inbred ICR , Reaction Time/drug effectsSubject(s)
Avoidance Learning/drug effects , Memory/drug effects , Panax , Plants, Medicinal , Polysaccharides/pharmacology , Animals , Avoidance Learning/physiology , Conditioning, Classical/drug effects , Conditioning, Classical/physiology , Dose-Response Relationship, Drug , Korea , Male , Memory/physiology , Plant Extracts/pharmacology , Rats , Reaction Time/drug effects , Reaction Time/physiology , Statistics, NonparametricABSTRACT
Effects of the ACTH4-7 pro-gly-pro, calcium valproate ("Germed", DDR) and nembutal on kindling preparation and audiogenic epilepsy were investigated. Development of after-discharges in response to repeated amygdaloid electrical stimulation was assessed in normal rats and in rats susceptible to audiogenic epilepsy (KM line of rats). ACTH4-7 pro-gly-pro had an anticonvulsant profile. ACTH4-7 pro-gly-pro decreased seizure threshold in the audiogenic epilepsy test, but did not prevent the motor convulsions.