Neuroprotective effect of peroxynitrite decomposition catalyst and poly(adenosine diphosphate-ribose) polymerase inhibitor alone and in combination in rats with focal cerebral ischemia.

OBJECT: The authors evaluated the neuroprotective effect of 5,10,15,20-tetrakis(N-methyl-4'-pyridyl)porphyrinato-iron(III) (FeTMPyP), a peroxynitrite decomposition catalyst, and 1,5-isoquinolinediol (ISO), a poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor, alone and in combination in rats with focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO). METHODS: Male Sprague-Dawley rats were subjected to 2 hours of MCAO followed by 22 hours of reperfusion. Cerebral infarction and neurological deficits were estimated after ischemia. Intraperitoneal injections of FeTMPyP (1 and 2 mg/kg) and ISO (0.05 and 0.1 mg/kg) were administered alone or in combination in ischemic animals. The PARP activity in vehicle- and drug-treated groups was estimated using anti-poly(ADP-ribose) antibody in immunofluorescence and immunoblotting studies. Two hours of MCAO and 22 hours of reperfusion produced significant cerebral infarction and neurological deficits. Treatment with FeTMPyP (1 and 2 mg/kg) and ISO (0.05 and 0.1 mg/kg) produced a significant reduction in cerebral infarction and neurological deficits. Combination therapy (2 mg/kg FeTMPyP and 0.1 mg/kg ISO) enhanced the inhibition of ischemic volume (77.81+/-0.86%) compared with monotherapies (FeTMPyP 54.07+/-5.6% and ISO 53.06+/-3.88%). Immunoblotting and immunofluorescence studies showed PARP activation after ischemia, which was reduced by drug treatment. CONCLUSIONS: Neuroprotection observed with FeTMPyP and ISO alone and in combination may be attributed to inhibition of the peroxynitrite-PARP cascade of cerebral ischemia/reperfusion injury.

Caprine enterotoxaemia associated with cerebral microangiopathy.

Cerebral microangiopathy is described in naturally occurring clostridial enterotoxaemia in two goats. The two cases were selected from the files of two diagnostic laboratories in Australia, on the basis that the clinical syndrome and history were consistent with a diagnosis of enterotoxaemia, and that the diagnosis was confirmed by the identification of epsilon toxin in the intestinal contents. The lesions consisted of acute perivascular proteinaceous exudate in the brain and bilaterally symmetrical foci of encephalomalacia were observed in one of the goats. These brain lesions confirm that Clostridium perfringens type D enterotoxaemia may produce histologically detectable brain changes in goats.

Spontaneous vascular mineralization in the brains of cows.

The frequency of occurrence and the characteristics of vascular mineralization in the brains of cows were studied. Mineralized lesions were found in the pallidal arteries in eight of 13 cows. They appeared as basophilic deposits in the arterial walls, were sheath-like or tubular in shape, and were accompanied by intimal oedema or fibrous thickening. The deposits were positive for periodic acid-Schiff, von Kossa's, alizarin red and Berlin blue stains. Elemental analysis revealed the presence of large amounts of phosphorus, calcium and zinc, as well as small amounts of iron, copper and sodium.