NERVE BLOOD FLOW IN NORMAL AND ISCHEMIC PERIPHERAL NERVE

描述（研究者摘要）：我们将继续研究

DESCRIPTION (Investigator's Abstract): We will continue our studies on nerve ischemia. Based on preliminary results of neuroprotection by. hypothermia, hyperbaric oxygenation (HBO), and free radical scavengers, we will evaluate these 3 strategies, of peripheral nerve neuroprotection from ischemic fiber degeneration (IFD). The hypothesis is that hypothermic neuroprotection occurs because nerve, with its large energy stores and low metabolic rate, is able to survive on.anaerobic metabolism, provided that its energy requirements are further reduced by hypothermia. The first specific aim is to define the therapeutic window of hypothermic neuroprotection, in terms of the degree and duration of hypothermia, and the maximal tolerated delay. The second aim is to evaluate the mechanism of this protect,ion. To achieve this, we will undertake the following 5 studies. We will evaluate (1) the effect of hypothermia on nerve energy metabolism, and (2) on glucose utilization ( 14 C-deoxyglucose). (3) We will evaluate if enhancing glucose transport (dihyarolipoic acid) or (4) increasing endoneuriaI glucose, will enhance neuroprotection. (5) Finally, we will test the notion that hyperglycemia will enhance rather than reduce neuroprotection because the large endoneurial space adequately buffers changes in nerve lactate or protons. The third aim is to evaluate the efficacy of HBO as neuroprotection. The fourth aim is to evaluate the effects of altering oxidative stress on neuroprotection. Our approach is specifically relevant to nerve, and we will use agents that can be used clinically. We will inhibit the arachidonic acid cascade with indomethacin. Reduced glutathione will be administered because of nerves very low activity of glutathione and its enzymes. Finally, we will use probucol, a-tocopherol, and lipoic acid, three lipophilic aunts that stop lipid peroxidation and has been used clinically. The fifth aim is to continue our studies of nerve vasoregulation. We will study vasopressin, neuropeptide Y, and cilostazol (vasodilator and phosphodiesterase inhibitor on nerve blood flow.