Summary In 3 mature female horses of varying breeds, episodes of colic and depression for 1–4 days preceded an encephalopathic disorder with maniacal behaviour, anxiety, profuse sweating and, in one case, terminal opisthotonus. Blood ammonia levels were elevated approximately 10‐fold. At necropsy, there were gastrointestinal serosal and mesenteric haemorrhages. Histologically, all 3 cases revealed diffuse Alzheimer type II astrocytes in the cerebral grey matter. Alzheimer type II astrocytes were glial fibrillary acidic protein (GFAP) negative or only weakly positive, weakly S‐100 positive, and vimentin negative. In the absence of primary hepatic and/or renal lesions, an increase in intestinal ammonia absorption due to ileus or increased ammonia production by colonic bacteria is hypothesised.

Sarcocystis neurona is an apicomplexan parasite that is the primary etiologic agent of equine protozoal myeloencephalitis in horses. Protective immune responses in horses have not been determined, but interferon-gamma (IFN-gamma) is considered critical for protection from neurologic disease in mice. The role of adaptive and innate immune responses in control of parasites was explored by infecting BALB/c, IFN-gamma knockout (GKO), and severe combined immune deficient (SCID) mice with S. neurona (10(4) sporocysts/mouse). Immune competent BALB/c mice eliminated parasites within 30 days, with no sign of neurologic disease, whereas GKO mice developed fulminant neurologic disease. In contrast, SCID mice remained healthy throughout the experimental period despite the persistence of parasite at low levels in some mice. Treatment with anti-IFN-gamma antibody resulted in neurologic disease in infected SCID mice. Although SCID mice lack adaptive immune responses, they have natural killer (NK) cells capable of producing significant quantities of IFN-gamma. Therefore, SCID mice were infected with sporocysts of S. neurona and treated with anti-asialo GM1. Depletion of NK cells, confirmed by flow cytometry, did not result in neurologic disease in SCID mice. These results indicate that IFN-gamma mediates protection from neurologic disease in SCID mice. Protective levels of IFN-gamma may originate from a low number of nondepleted NK cells or from a non-T cell, non-NK cell population.