Abstract

Domoic acid (DA), produced by marine algae such as Pseudo-nitzschia australis, is an excitatory neurotoxin that binds to glutamate receptors in the brain.¹ Exposure to DA has been shown to cause neurological disease in both humans and in animal species.^2,4 The first recognized marine mammal epizootic associated with DA producing plankton blooms occurred in 1998 along the California coast. During this event, approximately 400 California sea lions died or stranded with signs of neurological disease. Domoic acid was detected in the urine, serum, or feces of some of these animals.⁵ Since 1998, sea lions have stranded with signs of neurological disease at times when DA producing plankton blooms were not present along the Pacific coast and no DA was detected in body fluids. Clinical signs in sea lions with DA toxicosis include seizures, ataxia, disorientation, abnormal behavior, and abortion or in utero fetal death.² Some animals previously treated for DA toxicosis have re-stranded. Temporal lobe epilepsy and memory loss have been documented in humans after exposure to DA.^1,7 Therefore, sea lions exhibiting neurologic signs stranding outside of known DA producing plankton blooms may be exhibiting the effects of previous, sub-lethal exposure to the toxin. Current studies at The Marine Mammal Center and collaborating institutions are aimed at investigating the potential long-term effects of sub-lethal exposure to DA in California sea lions.

Pathologic findings in the brains of sea lions affected by DA exposure can vary. The most severe lesions are found in the anterior ventral hippocampus. In sea lions dying within seven days of stranding, lesions are characterized by acute ischemic neuronal necrosis, most severe in the pyramidal cells in zones CA4, CA3, and CA1 of the hippocampus and in the granular cells of the dentate gyrus. Neuropil vacuolation can be noted in the stratum lacunosum of the hippocampus. These lesions were commonly noted in sea lions with DA toxicosis that died during known plankton blooms between 1998 and 2000.⁶ In some animals that strand outside of known plankton blooms, hippocampal atrophy is noted on gross examination and there is relative enlargement of the adjacent lateral ventricles. Histological findings in these animals include neuronal loss, gliosis, perivascular lymphocytic cuffing, vascular endothelial hyperplasia, and edema in the hippocampus and dentate gyrus. Zones CA4, CA3, and CA1 of the hippocampus are often most severely affected, however, neuronal loss and gliosis can occur throughout the rhinencephalon. Malacia has been noted in the hippocampus and amygdala of several animals. These lesions are similar to those described in hippocampal sclerosis in humans with temporal lobe epilepsy.³ Acute neuronal necrosis has been less common in sea lions stranding outside of known plankton blooms. In some sea lions examined, lesions were more severe on one side of the brain. The cause of this apparent asymmetry is unknown. In some cases, affected areas of one of the hippocampi may have been inadvertently missed during tissue sectioning. Alternatively, unilateral lesions may reflect true asymmetry in lesion severity, as hippocampal sclerosis in humans with temporal lobe epilepsy is often asymmetric.³

Acknowledgments

The authors wish to thank the staff and volunteers of The Marine Mammal Center, and the pathology residents, especially Dr. Paul Silvagni, for initial review of some of the cases.

References

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