Cardiac arrest is a leading cause of death worldwide. While survival rates following sudden cardiac arrest remain relatively low, recent advancements in patient care have begun to increase the proportion of individuals who survive cardiac arrest. However, many of these individuals subsequently develop physiological and psychiatric conditions that likely result from ongoing neuroinflammation and neuronal death. The present study was conducted to better understand the pathophysiological effects of cardiac arrest on neuronal cell death and inflammation, and their modulation by the cholinergic system. Using a well validated model of cardiac arrest, here we show that global cerebral ischemia increases microglial activation, proinflammatory cytokine mRNA expression (interleukin-1, interleukin-6, tumor necrosis factor-␣), and neuronal damage. Cardiac arrest also induces alterations in numerous cellular components of central cholinergic signaling, including a reduction in choline acetyltransferase enzymatic activity and the number of choline acetyltransferasepositive neurons, as well as, reduced acetylcholinesterase and vesicular acetylcholine transporter mRNA. However, treatment with a selective agonist of the ␣7 nicotinic acetylcholine receptor, the primary receptor mediating the cholinergic anti-inflammatory pathway, significantly decreases the neuroinflammation and neuronal damage resulting from cardiac arrest. These data suggest that global cerebral ischemia results in significant declines in central cholinergic signaling, which may in turn diminish the capacity of the cholinergic anti-inflammatory pathway to control inflammation. Furthermore, we provide evidence that pharmacological activation of ␣7 nicotinic acetylcholine receptors provide significant protection against ischemia-related cell death and inflammation within a clinically relevant time frame.
Adult wethers (n = 750) were lot-fed for 13 days, 8 days or 3 days before a simulated voyage lasting 18 days to examine whether the period of lot-feeding affected the proportion of sheep that ate pelleted feed and their body weight change during simulated shipping. There was no significant difference in the proportion of non-feeders between treatment groups on days 7 and 14 of the voyage. Body weights were not significantly different between the treatment groups on days 14 and 18 of the voyage. Overall body weight loss, from the farm to the end of simulated shipping, was 4.08 kg (+/- 0.28, s.e.m.), 4.58 kg (+/- 0.28) and 4.51 kg (+/- 0.28) in sheep lot-fed for 13 days, 8 days and 3 days, respectively, and was not significantly different between treatments. It was concluded that lot-feeding for 13 days conferred no advantage in body weight or numbers of non-feeders compared with shorter periods in this study.
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