Title Page
Table of Content
List of Abbreviations

1.1 Statement of Research Problem
1.2 Justification
1.3 Theoretical Framework
1.4 Aims and Objectives
1.5       Statement of Research Hypothesis

2.0       Literature Review
2.1       Epilepsy
2.2       Etiology of Epilepsy
2.3       Types of Epilepsy
2.4       Classification of Seizures
2.4.1    Partial Seizures
2.4.2    Generalized Seizures (convulsive or non convulsive)
2.4.3    Unclassified Seizures
2.5 Ion Channels and Roles in Epilepsy
2.6 Action Potential and Seizure Development
2.7 Mechanisms of Epileptogenesis
2.7.1    Epileptogenesis and Ictogenesis
2.8       Neurotransmitter and Epilepsy
2.8.1Serotonin and Epilepsy
2.8.2Histamine and Epilepsy
2.9Basic Mechanism of Seizure Initiation and Propagation
2.9.1 Non-synaptic Mechanism of Seizure Initiation and Propagation
2.9.2 Synaptic Mechanism
2.10Diagnosis of Epilepsy
2.10.1 Neurological History
2.10.2 Physical Examination
2.10.3 Electroencephalography
2.10.4 Neuroimaging
2.11Treatment of Epilepsy
2.12Classifications of Antiepileptic Drugs
2.12.1Voltage Gated Sodium Channels Blockade
2.12.2 Voltage Gated Calcium Channels [VGCCS] Blockade
2.12.3 Reduction of Excitatory Glutaminergic Neurotransmission
2.12.4 Enhancement of GABA Mediated Inhibition
2.13The Plant (Laggera aurita)
2.13.1 Taxonomic classification
2.13.2 Local Names
2.13.3 Ethnomedicinal uses
2.13.4 Reported Phytochemical Constituents of the Plant
2.13.5  Medicinal Plants with Anticonvulsant properties

3.0Materials and Methods
3.1Plant Material, Collection and Authentication
3.2 Materials and Equipments
3.3Chemicals and Drugs
3.4       Experimental Animals
3.5       Plant Extraction
3.6       Preliminary phytochemical studies
3.6.3Test for Saponins
3.6.4 Test for Flavonoids
3.6.5 Test for Tannins
3.6.6 Test for Steroids and Terpenoids
3.6.7 Test for Cardiac Glycosides
3.7Acute Toxicity Studies(LD50Determination)
3.8       Anticonvulsant Studies
3.8.1    Maximal electroshock-Induced Seizures Test (MEST) in Chicks
3.8.2Pentylenetetrazole-Induced [Sc-PTZ] Seizure Test in Mice
3.8.3Strychnine-Induced-Seizure Test in Mice
3.8.4    Picrotoxin-Induced Seizure Test in Mice
3.8.5    Pentylenetetrazole-Induced Kindling Model in Rats
3.9       Interaction Studies using Maximal Electroshock Test
3.9.1    Effect of Co-administration of Methanol Leaf Extract of Laggera aurita and Fluphenamic Acid onMaximal Electroshock-Induced Seizures in Chicks
3.9.2    Effect of Co-administration of Methanol Leaf Extract of Laggera aurita and Cyproheptadine on Maximal Electroshock-Induced Seizure in Chicks
3.10     Statistical Analysis

4.1 Percentage Yield of the Plant Extract of Laggera aurita
4.2Phytochemical Constituents of Methanol Leaf Extract of Laggera aurita
4.3 Median Lethal Dose (LD50) Values of Methanol Leaf Extracts of Laggera aurita in Mice and Rats
4.4Effect of Methanol Leaf Extract of Laggera aurita on Maximal Electroshock-Induced Seizure in Chicks
4.5       Effect  of  Methanol  Leaf  Extract  of  Laggera  aurita  on  Pentylentetrazole Induced Seizures in Mice
4.6       Effect  of  Methanol  Leaf  Extract  of  Laggera  aurita  on  Strychnine-Induced Seizures in Mice
4.7       Effect of Methanol Leaf Extract of Laggera aurita on Picrotoxin –Induced Seizures in Mice
4.8       Effect of Concurrent Administration of Methanol Leaf extract of Laggera aurita and Fluphenamic Acid on Maximal Electroshock-Induced Seizures in Chicks
4.9       Effect of Concurrent Administration of Methanol Leaf Extract of Laggera aurita and Cyproheptadine on Maximal Electroshock-Induced Seizure in Chicks
4.10     Effect of Methanol Leaf Extract of Laggera aurita on Pentylenetetrazole-Induced Kindling in Rats

5.0       DISCUSSION


LaggeraauritaLinn. belongs to the family of Asteraceae. It is an annual herb which is found growing as weeds in Nigeria and spread throughout the sub-Saharan Africa. In Nigeria, Laggeraaurita is used asa remedy for pediatric malaria and in the management of epilepsy in Niger state, Nigeria Safiya, M, (personal communication, October 10, 2014). The study was conducted to evaluate the anticonvulsant potential of the methanol leaf extract of Laggeraaurita(LAME) using pentylenetetrazole induced seizure in mice, maximal electroshock induced seizure in chicks, picrotoxin induced seizure in mice and strychnine induced seizure in mice. Model of epilepsy involvingpentylenetetrazole induced kindling in ratsas well as interaction studieswas also conducted using fluphenamic acid and cyproheptadine. Extraction of 500g of the powdered leaves afforded a 20.4% yield. The preliminary phytochemical screening of the methanol leaf extract of Laggeraaurita revealed the presence of alkaloids, flavonoids, saponins, tannins, steroids/terpenoids, glycosides, carbohydrates, and cardiac glycosides. The oral median lethal dose (LD50) values for both species (rats and mice) was found to be greater than 5000 mg/kg while the i.p median lethal dose values for both species also was found to be 2154.06 mg/kg. In the maximal electroshock induced seizure model, the extract did not protect the animals against tonic hind limb extension (THLE), however it decreases the mean recovery time of the convulsed chicks. In the pentylenetetrazole-induced seizure model, the extract protected the mice by delaying the mean onset of seizure at all doses tested with significant p<0 .05="" 600="" 70="" acid="" against="" all="" an="" and="" at="" both="" but="" by="" channel.="" co-administration="" convulsed="" delaying="" doses="" effect="" enhanced="" extract="" fluphenamic="" i="" in="" increase="" indicating="" induced="" interaction="" intraperitoneal="" kg.="" kg="" mean="" mg="" mice="" minimal="""" modulatory="" of="" onset="" percentage="" picrotoxin="" possible="" produced="" protection="" seen="" seizure="" showed="" single="" sodium="" strychnine="" studies="" the="" there="" via="" was="" with="">i.p)
dose administration of the extract (600 mg/kg), phenytoin (20 mg/kg) and cyproheptadine (4 mg/kg) offered 40%, 100% and 0% protection against tonic hind limb extension respectively, while co-administration of cyproheptadine (4 mg/kg) and the extract (600 mg/kg) as well as the co-administration of cyproheptadine (4 mg/kg) and phenytoin (20 mg/kg) offered a reduced protection of 20% and 50% protection against seizurerespectively, these also indicate theinvolvement of serotonergic and histerminergic pathways in the anticonvulsant effect of the extract. The extract at all doses tested reduced the severity of seizure episodes induced by kindling. The results suggest that the methanol leaf extract ofLaggeraaurita possessessignificant anticonvulsant effects and has antiepileptogenic property.

The use of plants as medicine is an ancient practice common to all societies especially the African society and this practice continues to exist in the developing nations. It is on this basis that researchers keep searching for medicinal plants in order to produce the best for physiological uses as medicines (Usman and Osuji, 2007). The medicinal value of plants lies in some chemical substances that produce a definite physiological action in the human body. The most important of these bioactive compounds of plants are alkaloids, flavonoids, tannins and phenolic compounds (Edeoga et al.,2005). The use of medicinal plants as traditional medicines is well known in rural areas of many developing countries (Sandhu and Heinrich, 2005) and traditional healers claim that their medicine is cheaper, more effective and impart least side effects as compared to synthetic medicines. In developing countries, low-income people such as peasant farmers, people of small isolate villages and native communities use folk medicine for the treatment of common infections (Rojas et al.,2006). World Health Organization (WHO) encourages the inclusion of herbal medicines of proven safety and efficacy in the healthcare programs of developing countries (Amos et al., 2001).The degree of sensitization and mobilization by the WHO has encouraged some African countries to commence serious development on Traditional African medicine (Elujoba et al., 2005).

Epilepsy is a chronic disorder affecting both sexes (Blume et al., 2001). It is the second most chronic neurological condition seen by neurologist worldwide (Sridharan, 2002). Ithas no age, racial, social, sexual or geographical boundaries. Common causes include infectious, traumatic, metabolic or tumoral conditions or it may be idiopathic that is.....

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