Possible Mechanisms Of Cognitive Impairment Secondary To Epileptic Seizures

Epilepsy is a group of chronic diseases characterized by recurrent episodic central nervous system dysfunctions caused by abnormal discharges of neurons. The onset of epilepsy is most frequent in the first decade of life. Epidemiological investigations and clinical researches have confirmed that epilepsy, especially frequent recurrent seizures and status epilepsy, may result in cognitive impairment such as learning, memory and language deficits. For children whose brains are under development, frequent epileptic seizures may disturb the normal endo-environment for the development of brain functions, and consequently deteriorate the cognitive impairment indirectly. Seizure-related socio-psychological negative impacts may exacerbate the developmental situation and aggravate the cognitive impairment as well. Some symptoms of cognitive impairment may attenuate or disappear after seizure controlment; while others may last life long even after seizure freedom has been acquired and, inevitably, debase quality of life. Accordingly, cognitive impairment secondary to epilepsy became one of primary concerns of bothphysicians and patients.Clinical researches have garnered much of the interests in this area. Systematic researches aiming at uncovering the mechanisms of cognitive impairment secondary to epilepsy were just initiated recently. It has been freshly reported that seizures may result in synapse reorganization, mossy fiber sprouting, gliogenesis and neo-neurogenesis, which were frequently observed in epilepsy patients and animal models of different types. Abnormal changes in the level of neurotransmitters and their receptors in brain were proposed to be a cause of state-dependent cognitive impairment secondary to epilepsy. On the other hand, cognition is related to synapse reorganization, which is functioned by neurotransmitters. The long-term effects of recurrent seizures during developmental stage of life on cognitive functions and related neurochemical mechanisms have rarely, if any, been investigated.In the present study, rat model of epilepsy induce by pentylenetetrazol injection intraperitoneally were utilized to study effects of different ages of onset on subsequent cognitive impairment. Cognitive functions were evaluated with radiate arm maze and Morris water maze respectively. Functions and roles of NO-NOS in limbic system were assessed by immunohistochernical methods and using of an NO precursor, sodium nitroprusside. The activity of ChAT in rat brain after epileptic seizures was evaluated by Engel method and AChE by Ellman method, and the relationship between the activities of the two enzymes and cognitive functions was assessed. The interrelationship of cognitive impairment and re-distribution of muscarinic acetylcholine receptors in developing brain following repetitive epileptic seizures was investigated. For the purposes of prevention and early treatment, the remedial effects of perinatal choline supplement in diet on the cognitive impairment secondary to epilepsy was also evaluated and the possible mechanisms proposed.Results of present studies showed that epileptic seizures induced in both adult and immature rats could cause learning and memory deficit. Cognitive dysfunctions were more severe in immature rats than in adult rats. The degree of impairment was age dependent. Compared with seizures onset at ages of 14, 21 and 28 days, seizures onset at age of 7 days resulted in more prominent cognitive impairment. The degree of impairment was correlated with the decrease of muscarinic acetylcholine receptors in hippocampus. It was observed that NOS immuno-positive neurons in hippocampus and cortex were increased shortly after epileptic seizure, and simultaneously, visual spatial learning and memory evaluated by radiate maze was declined. Pre-seizure supplement of sodium nitroprusside, an NO donor, could attenuate the cognitive impairment after seizure without changing the distribution of NOS immuno-positive neurons in hippocampus and cortex.Following points can be conclud...