Neuroprotective effects of free radical scavengers in stroke.

Acute ischaemic stroke is a leading cause of death in the majority of industrialised countries and also in many developing countries. Free radicals are generated in the brain during ischaemic injury and these radicals are involved in the secondary injury processes. Several free radical scavengers have been developed and some of them have progressed into clinical trials. One of them, edaravone, has been approved by the regulatory authority in Japan for the treatment of stroke patients. Another scavenger, disodium 4-[(tert-butylimino)methyl] benzene-1,3-disulfonate N-oxide (NXY-059; disufenton), has demonstrated efficacy in a phase III clinical trial (SAINT [Stroke Acute Ischaemic NXY-059 Treatment study]-I) involving a large number of stroke patients. Unfortunately, SAINT II did not show efficacy in the treatment of stroke patients. The purpose of this article is to review the current development of antioxidant strategies, update recent findings for NXY-059 in the treatment of stroke patients, and discuss the future development of neuroprotective agents. Although the development of neuroprotective strategies for the treatment of stroke is challenging, progress in molecular and cellular neuroscience will uncover new information about stroke mechanisms, which should result in the realisation of neuroprotective therapy for this disease.

Effects of amino acid deficiency on monoamines in the lateral hypothalamus (LH) in rats.

Animals decrease intake of an indispensable amino acid deficient diet, due in part to decreased dietary limiting amino acid concentrations within the anterior piriform cortex (APC). In addition to studies supporting a primary role for the APC in this phenomenon, recent studies have shown that the lateral hypothalamus (LH), which receives projections from the APC, also mediates the anorectic response to amino acid deficiency. The neurochemical changes within the LH that accompany the anorexia to amino acid deficiency are unclear. We hypothesized that norepinephrine (NE), dopamine (DA) and serotonin, whose levels are altered in response to amino acid deficiency within the APC, also act within the LH to mediate amino acid deficiency-induced anorexia. We determined that ingestion of an amino acid devoid diet increased concentrations of NE and the serotonin metabolite, 5-hydroxyindoleacetic acid in the LH. The 5-hydroxytryptamine metabolite was increased overall, according to analysis by area under the curve. Individual points reached significance at 130 min; NE was elevated at 170 min. These results suggest that the sustained anorectic response following ingestion of an amino acid devoid diet may be associated with increased activity of the NE and 5-hydroxytryptamine systems in the LH.