STANFORD School of Medicine

CONTENTS:      Focus

Main Topics

Lab Members

Publications

PICTURES:       Hippocampus

Mechanism of astrocyte

Neurons

Astrocytes in a Brain Slice

Neurons and Astrocytes in Culture

EXTERNAL LINKS:

Anesthesia Department

Neuroscience Program

Stanford School of Medicine

The Giffard Lab

 Surviving Cerebral Ischemia

 

Rona G. Giffard, Ph.D., M.D.      
Department of Anesthesia
Grant Building S272
Stanford University School of Medicine
Stanford, CA 94305-5117
 
Email address: rona.giffard@stanford.edu

 


Research Focus
 
Our research focus is cerebral ischemia-understanding how brain cells are injured and developing ways to reduce or prevent this injury.  Most of our work is performed in primary cell culture and animal stroke models with a focus on glial cell injury as well as neuronal injury.

 

Specific Topics

  • Gene therapy for stroke with heat shock proteins (hsp70, hsp-40, hsp60 and hsp27), antiapoptotic proteins (bcl-2 and bcl-x) and antioxidant proteins (SOD1 and 2, catalase and glutathione peroxidase)

  • Role of astrocyte impairment in global ischemia

  • Cell type specific injury studying isolated neurons, astrocytes, microglia and endothelial cells

  • Cell-cell interactions of theses cell types during injury using different types of mixed cultures, brain slices, and transgenic animals.

  • Role of inflammation in injury

  • Regulation of pH, bicarbonate transporters

  • Effects of development on vulnerability to injury and type of cell death

                                                             

                                                                     Hippocampus

                             

               Upper panel is a diagram of the hippocampus showing the region from which the lower
               photomicrographs were taken.
               Lower left panel is a photomicrograph of a control hippocampal slice culture showing
               immunoreactivity for glutamate transporter 1 (green), counterstained with propidium
               iodide (red) to show nuclei.
               Lower right panel is of a similar culture subjected to transient in vitro ischemia ex-
               hibiting selective reduction of glutamate transporter 1 immunoreactivity (green) in the
               CA1 region as compared to dentate gyrus (DG) at an early recovery time. 

               

              Proposed mechanism of astrocyte contribution to delayed neuronal death

                                    

             Transient forebrain ischemia selectively decreases mitochondrial membrane potential
             (Δψm) and increases reactive oxygen species (ROS) in CA1 astrocytes. The greater
             production of ROS leads to astrocyte impairment including oxidative damage of  
             glutamate transporter 1 (GLT-1) on the astrocyte membrane. The loss of GLT-1
             contributes to the increase of extracellular glutamate and excitoxicity of the pyramidal
             neurons.



Main Topics

  • Gene therapy of stroke

    We are currently using transgenic mice and retroviral expression in primary culture to study the effects of changes in gene expression on cell survival from ischemia and ischemia-like injuries. Genes currently under study are hsp70, bcl-2, bcl-x, SOD1, and 2.

    Two Views of a Primary Culture
    Neurons and Astrocytes


    NSE Stained                                                                                  GFAP Stained

     
     

     

  • Effects of acidosis during ischemia, regulation of pH in ischemia

    We have cloned a splice variant of the sodium bicarbonate cotransporter and 2 splice variants of the sodium dependent chloride bicarbonate exchanger.  We are currently studying their physiological role and regulation.


 

Members of the Lab

Lab Location:  Grant Building S278

Phone: 650-723-7839

Fax: 650-725-8052

  Lijun Xu, M.D.
Research Associate
  Yi-Bing Ouyang, Ph.D.
Research Associate
  Xiaoyun Sun, M.D.
Research Associate
  John Emery, Ph.D.
Research Assistant
  Luda Voloboueva, Ph.D.
Postdoc
  Xiaoxing Xiong, Ph.D.
Postdoc
  Jaimie Adelson
Medical Student


   

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Last Updated: 05/18/07
Comments or questions: jennyjhu@stanford.edu