Annals of the New York Academy of Sciences
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Ann. N. Y. Acad. Sci. · Oct 1997
ReviewInflammatory gene expression in cerebral ischemia and trauma. Potential new therapeutic targets.
This review summarized evidence in support for the case that ischemia elicits an inflammatory condition in the injured brain. The inflammatory condition consists of cells (neutrophils at the onset and later monocytes) and mediators (cytokines, chemokines, others). It is clear that de novo upregulation of proinflammatory cytokines, chemokines and endothelial-leukocyte adhesion molecules in the brain follow soon after the ischemic insult and at a time when the cellular component is evolving. ⋯ However, it should be kept in mind that cytokines were also argued to provide beneficial effects in brain injury as inferred from studies with TNF-receptor knock-out mice (p55 and p75 knock-out), which display increased sensitivity to brain ischemia, and the capacity of IL-1 to elicit the state of ischemic tolerance upon repeated administration. Nevertheless, the recent revelation on the capacity of ischemia to induce acute inflammation in the brain provides a new and fertile ground for new explorations for novel therapeutic agents that could confine the neuronal damage that follows ischemia. Furthermore, many of the genes that are upregulated by ischemia have growth-promotion capacity and therefore raise the possibility that such gene products may be useful in counteracting brain damage by enhancing repair and establishing compensatory mechanisms that enhance histological and functional recovery.
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We have characterized the activation of the HPA axis in the chronic inflammatory stress model of adjuvant-induced arthritis. Alteration in the hypothalamic control mechanism, where CRF is no longer the major corticotrophin-releasing factor, has been noted in a number of other immune-mediated disease models, including experimental allergic encephalomyelitis, eosinophilia myalgia syndrome, systemic lupus erythematosus, and leishmaniasis. These changes occur in both the mouse and the rat, suggesting this may be a common mechanism to chronic immune activation. ⋯ We have demonstrated that central neurotransmitter systems are able to influence the severity of peripheral inflammation. In particular we have shown that depletion of serotonin at the time of the development of the inflammatory episode reduces the severity of the inflammation. These findings suggest the possibility of novel therapeutic strategies targeting neurotransmitter systems to alleviate inflammation.
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Ann. N. Y. Acad. Sci. · Mar 1997
The effect of opioids on thermoregulatory responses in humans and the special antishivering action of meperidine.
In summary, both mu-receptor and combined mu/kappa-receptor opioids impair thermoregulatory control. Alfentanil, a pure mu-receptor agonist slightly increased the thresholds for sweating and markedly decreased the thresholds for vasoconstriction and shivering. However, the vasoconstriction-to-shivering range remained normal during alfentanil administration as it does during general anesthesia. ⋯ However, meperidine reduced the shivering threshold twice as much as the vasoconstriction threshold, thus significantly increasing the vasoconstriction-to-shivering range. Furthermore, shivering during meperidine administration, once triggered, was of low intensity suggesting that the drug also decreased the gain of shivering. The special antishivering action of meperidine appears to result, at least in part, from its kappa-receptor activity.