Exacerbation of lymphocytic choriomeningitis in mice treated with the inducible nitric oxide synthase inhibitor aminoguanidine

To elucidate the possible involvement of the inducible nitric oxide synthase (iNOS) and NO in the development of lymphocytic choriomeningitis (LCM), the consequences of inhibition of iNOS by the inhibitor aminoguanidine was examined in mice following intracerebral infection with LCM virus (LCMV). Aminoguanidine administration to mice infected with LCMV completely blocked increased plasma nitrate/nitrite levels and led to increased proinflammatory cytokine gene expression at early stages of lesion development in the brain, enhanced clinical severity and decreased survival time. The levels of LCMV recovered from the brain of aminoguanidine treated mice did not differ from those in infected control mice. These findings argue against either an anti-viral or pathogenic role of NO in LCM but rather suggest a possible protective action of this mediator.     

Effect of temperature in focal ischemia of rat brain studied by 31P and 1H spectroscopic imaging

³¹P, ¹H and lactate spectroscopic imaging was used to evaluate the effects of hypothermia on focal cerebral ischemia produced by middle cerebral artery occlusion. The effects on high energy phosphate metabolism, pH, lactate and NAA were investigated in 24 spontaneously hypertensive rats subjected to either permanent or transient ischemia. Under either normothermic (37.5°C) or hypothermic (32°C) conditions, with permanent 6-h occlusion, there was little difference between groups in either the NMR measurements or the volume of infarction. In animals that underwent 3 h of ischemia followed by 12 h of reperfusion, the ischemic changes in lactate, pH, NAA, and high-energy phosphate returned toward control values, and there was a protective effect of hypothermia (infarct volume of 211 ± 26 and 40 ± 14 mm³ in normothermic and hypothermic groups, respectively). Thus, hypothermia did not ameliorate the changes in lactate, pH, NAA, or high energy phosphate levels occurring during ischemia, however, during reperfusion there was an improvement in both the recovery of these metabolites and pathological outcome in hypothermic compared with normothermic animals.