Abstract

A 7-year-old, stranded, male California sea lion with epilepsy due to left hippocampal atrophy likely caused by domoic acid toxicosis was deemed non-releasable. Over the previous 2 years, he became refractory to antiepileptic drugs (phenobarbital 1.6 mg/kg SID and diazepam 0.05 mg/kg BID) and developed life-threatening periods of anorexia. Eight convulsive seizures were observed in the 2 weeks prior to surgery. A novel interneuron-based cell transplantation using GABA progenitor cells from porcine embryonic medial ganglionic eminence (MGE) was performed with the goal to eliminate seizures and improve “quality of life” measures.^1,2 Porcine MGE progenitor cells (50,000 cells/site) were surgically transplanted into four locations in the damaged hippocampus and entorhinal cortex. Sea lion MRI and CT imaging data were used to guide the stereotaxic surgical procedure. Immunosuppressive doses of cyclosporine (3 mg/kg BID) and dexamethasone (0.17 mg/kg SID) were given pre- and post-transplantation. At 60 days post-transplant, no seizures nor neurological deficits have been observed, and the sea lion’s appetite and weight are stable. Over the next 4 months, the immunosuppressive drug regimen will be tapered down. In addition, based on observed seizure activity and behaviors, antiepileptic drugs will be slowly withdrawn. This novel surgical procedure case study demonstrates the potential to successfully xenotransplant porcine MGE interneurons into sea lions for potential resolution of refractory epilepsy.

Acknowledgements

The authors wish to thank the sea lion training staff at Six Flags Discovery Kingdom for the care and training of the sea lion and the staff at SAGE Veterinary Centers for providing imaging and surgical support.

*Presenting author

Literature Cited

1.  Casalia ML, Li T, Ramsay H, Ross PJ, Paredes MF, Baraban SC. 2020. Pallial interneuron origins in the embryonic porcine medial ganglionic eminence. J Neurosci. Provisionally accepted.

2.  Hunt RF, Girskis KM, Rubenstein JL, Alvarez-Buylla A, Baraban SC. 2013. GABA progenitors grafted into the adult epileptic brain control seizures and abnormal behavior. Nat Neurosci. 16:692–697.