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 i s 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 i s to evaluate the efficacy of HBO as neuroprotection.
The fourth aim i s 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.
| Kimpinski, Kurt; Iodice, Valeria; Sandroni, Paola et al. (2012) Sudomotor dysfunction in autoimmune autonomic ganglionopathy: a follow-up study. Clin Auton Res 22:131-6 |
| Geser, F; Malunda, J A; Hurtig, H I et al. (2011) TDP-43 pathology occurs infrequently in multiple system atrophy. Neuropathol Appl Neurobiol 37:358-65 |
| Kimpinski, Kurt; Iodice, Valeria; Sandroni, Paola et al. (2010) Effect of pregnancy on postural tachycardia syndrome. Mayo Clin Proc 85:639-44 |
| Figueroa, Juan J; Basford, Jeffrey R; Low, Phillip A (2010) Preventing and treating orthostatic hypotension: As easy as A, B, C. Cleve Clin J Med 77:298-306 |
| Kimpinski, Kurt; Iodice, Valeria; Low, Phillip A (2010) Postural Tachycardia Syndrome associated with peripartum cardiomyopathy. Auton Neurosci 155:130-1 |
| Iodice, V; Kimpinski, K; Vernino, S et al. (2009) Efficacy of immunotherapy in seropositive and seronegative putative autoimmune autonomic ganglionopathy. Neurology 72:2002-8 |
| Kimpinski, K; Iodice, V; Sandroni, P et al. (2009) Sudomotor dysfunction in autoimmune autonomic ganglionopathy. Neurology 73:1501-6 |
| Kimpinski, Kurt; Iodice, Valeria; Vernino, Steve et al. (2009) Association of N-type calcium channel autoimmunity in patients with autoimmune autonomic ganglionopathy. Auton Neurosci 150:136-9 |
| Wang, Annabel K; Fealey, Robert D; Gehrking, Tonette L et al. (2008) Patterns of neuropathy and autonomic failure in patients with amyloidosis. Mayo Clin Proc 83:1226-30 |
| Vogel, Elizabeth R; Corfits, Jeanne L; Sandroni, Paola et al. (2008) Effect of position on valsalva maneuver: supine versus 20 degree position. J Clin Neurophysiol 25:313-6 |
Showing the most recent 10 out of 105 publications
