Veterinary Students in Research

This winning submission to our Cases and Abstracts category comes from Tierra Rose from Purdue University. The abstract is from her summer research project at Stanford University School of Medicine that focused on temporal lobe epilepsy in sea lions along the Monterey Bay region of California due to domoic acid toxicity. Great job Tierra!

Loss of parvalbumin-immunoreactive interneurons in epileptic California sea lions

Tierra Rose¹, Starr Cameron², Raisa Glabman3, Emily Abrams², Shawn Johnson4, Frances Gulland4, Paul Buckmaster²

¹Purdue University, College of Veterinary Medicine, West Lafayette, IN
²Stanford University, School of Medicine, Department of Comparative Medicine, Stanford, CA
³University of Pennsylvania, School of Veterinary Medicine, Philadelphia, PA
4Marine Mammal Center, Sausalito, CA

Temporal lobe epilepsy is common in humans. Seizures typically originate in the hippocampus, but the cause is unknown. The hippocampal dentate gyrus of human patients displays neuropathological abnormalities, including the loss of parvalbumin-immunoreactive interneurons. Normally, parvalbumin interneurons strongly inhibit excitatory neurons. Loss of parvalbumin interneurons in temporal lobe epilepsy might cause seizures. Rodent models of temporal lobe epilepsy fail to replicate the parvalbumin interneuron loss found in human patients, so better animal models are needed. California sea lions (Zalophus californianus) develop temporal lobe epilepsy after exposure to the excitatory neurotoxin domoic acid, which enters the marine food chain during harmful algal blooms. We hypothesized that epileptic sea lions would display significant loss of parvalbumin interneurons in the dentate gyrus. To test this hypothesis, sea lions were intracardially perfused with formaldehyde immediately upon euthanasia because of failed response to treatment and poor prognosis. Brains were sectioned (40 μm) coronally. Hippocampi were isolated and processed for parvalbumin-immunocytochemistry. Stereology and a Neurolucida system are being used to estimate the number of parvalbumin-positive interneurons per dentate gyrus. Preliminary data suggest that epileptic sea lions display severe loss of parvalbumin interneurons, similar to human patients with temporal lobe epilepsy. If confirmed, these findings would suggest that epileptic sea lions can be used as a large animal model of human temporal lobe epilepsy. Sea lions could serve as candidates to test novel anti-epileptogenic treatments before human clinical trials.

Student: Supported by NIH Office of the Director, Division of Comparative Medicine
Research: Supported by NSF and NIH (NINDS & OD)