Research

Neuro Anesthesia

The laboratory is focused upon the study of the pathophysiology of ischemic cerebral injury and the means by which the magnitude of this injury can be reduced in experimental animals.  To that end, our current efforts involve:

  •  The study of ischemic preconditioning (IPC) of the brain
  •  Approach involves use of in vivo models of cerebral ischemia (global, focal and forebrain ischemia) in rats and mice
  • Two approaches to the study of the mechanisms by which IPC induces tolerance
  • First, use of microarray technology to screen and identify candidate genes that might mediate tolerance
  • Confirmation of microarray results obtained by PCR and expression of protein confirmed by immunofluorescence and Western blotting
  • Goal is to manipulate candidate genes with siRNA technology to determine the role that they play in acquisition of tolerance 
  • Work in this area has led to the identification of growth factor, reactive oxidative species, cellular energetics, and the Wnt-b catenin pathways as key players in IPC
  • Second, we have begun studies of signaling pathways that are activated by NMDA receptor activation. Specifically, we are interested in role that Src family kinases play in tolerance. 
  • Work in this area shows Src plays a central role in NMDA mediated IPC, and that caveolin, which scaffolds Src and the NMDA receptor, facilitates coordinated signaling that induces tolerance
  • A putative peptide Src activator has been synthesized and will be TAT conjugated 
  • Studies currently underway will determine whether activation of Src downstream of the NMDA receptor leads to tolerance. 
  • If proven true, the peptide activator that we synthesized will be a novel means by which IPC can be induced pharmacologically
  • Trainees that participate in laboratory research will participate in these projects and receive training in in vivo models of IPC and cerebral ischemia
  •  In vitro models of IPC and ischemia (neuronal cell cultures and hippocampal slices), and modern methods of molecular biology (PCR, various blotting techniques, siRNA, microRNA, transfection and transgenics, etc)
  • Collectively, the trainees will develop expertise in the study of preconditioning from individual cells to the whole animal

Selected Publications 

Head BP, Patel HH, Tsutsumi YM, Hu Y, Mejia T, Mora RC, Insel PA, Roth DM, Drummond JC, Patel PM. Caveolin-1 expression is essential for N-methyl-D-aspartate receptor-mediated Src and extracellular signal-regulated kinase 1/2 activation and protection of primary neurons from ischemic cell death Faseb J. 22:828-840, 2008.

Drummond JC, Dao AV, Roth DM, Cheng CR, Atwater BI, Minokahdeh A, Pasco LC, Patel PM. Effect of dexmedetomidine on cerebral blood flow velocity, cerebral metabolic rate, and carbon dioxide response in normal humans Anesthesiol. 108:225-232, 2008.

Head B.P., Patel P Anesthetics and brain protection. Curr Opin Anesthesiology 20:395-399, 2007.

Drummond JC, McKay LD, Cole DJ, Patel PM. The role of nitric oxide synthase inhibition in the adverse effects of etomidate in the setting of focal cerebral ischemia in rats. Anesth. Analg. 100:841-846, 2005.

 Inoue S, Drummond JC, Davis DP, Cole DJ, Patel PM.  Combination of isoflurane and caspase inhibition reduces cerebral injury in rats subjected to focal cerebral ischemia. Anesthesiology. 101:75-81, 2004

Kawaguchi M, Drummond JC, Cole DJ, Kelly PJ, Spurlock MP, Patel PM.Effect of isoflurane on neuronal apoptosis in rats subjected to focal cerebral ischemia. Anesth Analg. 98:798-805,2004

Cole DJ, Cross LM, Drummond JC, Patel PM, Jacobsen WK. Thiopentone and methohexital, but not pentobarbitone, reduce early focal cerebral ischemic injury in rats. Can J Anaesth. 48:807-14,2001