Sustained oxidative stress is a known sequel to focal cerebral ischemia. This study examined the effects of treatment with a single dose or sustained infusion of the redox-modulating MnPorphyrin Mn III TDE-2-ImP 5+ on outcome from middle cerebral artery occlusion (MCAO) in the rat. Normothermic rats were subjected to 90 min MCAO followed by 90 min reperfusion and then were treated with a single intracerebroventricular dose of Mn III TDE-2-ImP 5+ . Neurologic and histologic outcomes were assessed at 1 or 8 weeks post-ischemia. A single dose of Mn III TDE-2-ImP 5+ caused a dose-dependent improvement in histologic and neurologic outcome when assessed 1 week postischemia. Mn III TDE-2-ImP 5+ afforded preservation of brain aconitase activity at 5.5 hrs after reperfusion onset, consistent with its known antioxidant properties. Mn III TDE-2-ImP 5+ also attenuated post-ischemic NF-κ B activation. Evidence for effects on cerebral infarct size and neurologic function had completely dissipated when rats were allowed to survive for 8 weeks postischemia. In contrast, a 1-week continuous intracerebroventricular Mn III TDE-2-ImP 5+ infusion caused persistent and substantive reduction in both cerebral infarct size and neurologic deficit at 8 weeks post-ischemia. Pharmacologic modulation of post-ischemic oxidative stress is likely to require sustained intervention for enduring efficacy in improving neurologic and histologic outcome from a transient focal ischemic insult.
Euglandina rosea, a predatory land snail, tracks prey and mates by following slime trails. Euglandina follow slime trails more than 80% of the time, following trails of their own species, but not those of prey snails, in the direction that they were laid. The attractive elements of prey slime are small, water-soluble compounds detected by specialized lip extensions. Although olfaction plays no role in trail following, strong odors disrupt tracking. Inhibition of nitric oxide synthase also disrupts slime trail following, suggesting a role for nitric oxide in neural processing of slime trail stimuli. Euglandina can be conditioned to follow novel trails of glutamate or arginine paired with feeding on prey snails. These experiments demonstrate that slime-trail tracking in Euglandina is a robust, easily measured behavior that makes a good model system for studying sensory processing and learning in a novel modality.
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