What is the role of Neurokinin-B in seizures and epilepsy in C57Bl/6J mice?

Abstract

Every year 180,000 Americans are diagnosed with epilepsy, a chronic neurological disorder that is characterized by spontaneous seizures. It is known that neuropeptides such as Substance P are involved in seizure initiation and maintenance, however limited studies have explored the role of Neurokinin-B (NKB). To better understand the role of this neuropeptide in seizures, we are developing NKB-over expressing transgenic mice in a C57Bl/6J background. In this study, we investigate various seizure models that can be used in our transgenic lines, focusing on long-lasting seizures known as status epilepticus (SE). Additionally, we look at NKB expression in both rats and mice after SE. In rats, lithium-pilocarpine showed complete success with 100% entering SE, however only 20% mice entered status. Ongoing studies include the addition of the physostigmine and electrical stimulation of the hippocampus. In animals reaching SE, brain tissue was examined using hemotoxylin and eosin staining to image actively dying cells and immunohistochemistry to reveal NKB expression. Cell death, evidenced by eosin, showed fluorescence in the thalamic nuclei and hippocampus, suggesting that these regions are most susceptible to damage resulting from seizures. Results from the immunohistochemistry showed an upregulation of NKB in the striatum, thalamic nuclei, substantia nigra and hippocampus. Discovering a role for NKB in seizure initiation and maintenance in these animal models could lead to better therapeutic strategies for humans with epilepsy.