Regulating synaptic protein expression by in vivo antibody treatment to reduce epileptogenesis phase in rats
Abstract: Epilepsy is a neurological disorder characterized by its debilitating epileptic seizures. There are generalized seizures, which affect the whole brain at once, and focal seizures, which start from one part of the brain. The most common focal epilepsy, is temporal lobe epilepsy representing almost 70% of all focal epilepsies. Around 30% of all patients are therapy refractory, therefore there is a huge demand to find new drugs and ways to help all patients with epilepsy. It has been previously found that synaptic proteins play a crucial role in epilepsy, and in previous studies the protein N-cadherin has been found to be decreased 4 weeks after induced epilepsy in rats that did develop spontaneous seizures. In this study we set out to modulate n-cadherin protein expression with antibodies in order to evaluate if this could potentially be a novel method to reduce seizure frequency and seizure-induced cognitive deficits. For a more clinically realistic scenario some animals were given a combinatorial treatment of the antibody and an anti-epileptic drug named Keppra to see if any synergistic effect can be achieved. In the first pilot study we infused N-cadherin antibody for 1 and 2 weeks to study the antibody distribution and suitable antibody concentration that would not induce overt morphological changes. In addition, we evaluated the behaviour of the rats. The preliminary results show that rats induced with 1000µg/ml antibody over the course of two weeks show no signs of bad health, although they had a tendency to be more anxious than the untreated rats. Future studies will reveal if N-cadherin antibody treatment has any effects on seizure frequency.
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