Rona G. Giffard

Title
Associate Professor

Department
Anesthesia

Research Interests
Cellular and molecular basis for neuronal and astrocyte vulnerability to ischemic injury.

Email
rona.giffard@stanford.edu

Phone
725-8482

Fax
725-8052

Address
Grant S274
Mail Code: 5117
http://giffardlab.stanford.edu/

Faculty Research Description
Brain injury from stroke, head trauma, and chronic neurologic degenerative diseases is a major cause of morbidity and mortality in this country. We are particularly interested in the cellular consequences of brain injury. To study this problem we work with primary cultures of neurons and astrocytes from mice. Current work focuses on:
1) the role of astrocytes in brain injury;
2) the interaction of neurons and glia during injury;
3) the role of heat shock response and hsp70overexpression in neuronal and astrocytic injury;
4) the role of oxidative stress in injury;
5) the effects of pH changes on the vulnerability of neurons and glia to injury;
6)the action of pH regulatory transporters during ischemia
7) the use of antiapoptotic genes such as bcl-2 to protect neurons and astrocytes.

We use gene transfer techniques including retroviral vectors to express genes of interest in brain cells and analyze ways in which these genes can provide protection. We analyze the effects using fluorescent probes for pH, intracellular calcium, glutathione, as well as morphologically evaluating outcome, and quantitating injury. Currently we are also conducting transgenic mouse experiments to analyze the effects of overexpression or loss of expression of specific genes on outcome from stroke.

A new area of interest is differences in pH regulation by neurons and astrocytes during ischemia, and the role of bicarbonate transport in astrocyte vulnerability to ischemic injury. Cloned transporters from brain are being studied for their physiological roles as well as for structure function analysis of members of this family of transporters.

Giffard RG, Papadopoulos MC, van Hooft JA, Xu L, Giuffrida R, Monyer H The electrogenic sodium bicarbonate cotransporter: developmental expression in rat brain and possible role in acid vulnerability. J Neurosci. 2000 Feb 1;20(3):1001-8.

Xu L, Koumenis IL, Tilly JL, Giffard RG Overexpression of bcl-xL protects astrocytes from glucose deprivation and is associated with higher glutathione, ferritin, and iron levels. Anesthesiology. 1999 Oct;91(4):1036-46.

Xu L, Glassford AJM, Giaccia AJ, Giffard RG. Acidosis reduces neuronal apoptosis. Neuroreport 9:875-879, 1998.

Papadopoulos, M. C., Koumenis, I.L., Xu, L., and Giffard, R.G. Potentiation of murine astrocyte antioxidant defense by bcl-2: protection in part reflects elevated glutathione levels. European Journal of Neuroscience, 10: 1252-1260, 1998.

Newcomb R, Sun X-Y, Taylor L, Curthoys N, Giffard RG. Increased production of extracellular glutamate by the mitochondrial glutaminase following neuronal death. Journal of Biological Chemistry 272 {17}: 11276-82, 1997.

Papadopoulos MC, Sun X, Cao J, Mivechi N, Giffard RG. Overexpression of HSP-70 protects astrocytes from combined oxygen-glucose deprivation. Neuroreport. 7(2):429-432, 1996.

Areas of Study
Cellular Neurobiology
Molecular Neurobiology
SBRC
Ph.D.