title: Hippocampal neuropathology of domoic acid-induced epilepsy in California sea lions (Zalophus californianus).
abstract: California sea lions (Zalophus californianus) are abundant human-sized carnivores with large gyrencephalic brains. They develop epilepsy after experiencing status epilepticus when naturally exposed to domoic acid. We tested whether sea lions previously exposed to DA (chronic DA sea lions) display hippocampal neuropathology similar to that of human patients with temporal lobe epilepsy. Hippocampi were obtained from control and chronic DA sea lions. Stereology was used to estimate numbers of Nissl-stained neurons per hippocampus in the granule cell layer, hilus, and pyramidal cell layer of CA3, CA2, and CA1 subfields. Adjacent sections were processed for somatostatin immunoreactivity or Timm-stained, and the extent of mossy fiber sprouting was measured stereologically. Chronic DA sea lions displayed hippocampal neuron loss in patterns and extents similar but not identical to those reported previously for human patients with temporal lobe epilepsy. Similar to human patients, hippocampal sclerosis in sea lions was unilateral in 79% of cases, mossy fiber sprouting was a common neuropathological abnormality, and somatostatin-immunoreactive axons were exuberant in the dentate gyrus despite loss of immunopositive hilar neurons. Thus, hippocampal neuropathology of chronic DA sea lions is similar to that of human patients with temporal lobe epilepsy.
authors.affiliation: Department of Comparative Medicine, Stanford University, Stanford, California, 94305; Department of Neurology & Neurological Sciences, Stanford University, Stanford, California, 94305.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Buckmaster
authors.forename: Xiling
authors.initials: X
authors.lastname: Wen
authors.forename: Izumi
authors.initials: I
authors.lastname: Toyoda
authors.forename: Frances M D
authors.initials: FM
authors.lastname: Gulland
authors.forename: William
authors.initials: W
authors.lastname: Van Bonn
mesh_terms: D000367:Age Factors; D000818:Animals; D002452:Cell Count; D002908:Chronic Disease; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology* / Q000662:veterinary*; D004833:Epilepsy, Temporal Lobe / Q000473:pathology; D005260:Female; D007839:Functional Laterality; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D008297:Male; D008387:Marine Toxins / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D012598:Sclerosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000662:veterinary; D046070:Sea Lions / Q000378:metabolism; D012737:Sex Factors; D013004:Somatostatin / Q000378:metabolism; D013045:Species Specificity
chemical_list: D008387:Marine Toxins; D013004:Somatostatin; C012301:domoic acid; D007608:Kainic Acid
keywords: dentate gyrus; hippocampal sclerosis; mossy fiber sprouting; somatostatin; stereology