Selective dysfunction of hippocampal CA1 astrocytes contributes to delayed neuronal damage after transient forebrain ischemia.
Transient global ischemia, as with cardiac arrest, causes loss of CA1 hippocampal neurons 2-4 d later, whereas nearby dentate gyrus (DG) neurons are relatively resistant. Whether differential astrocyte vulnerability in ischemic injury contributes to CA1 neuronal death is uncertain. Here, we find that CA1 astrocytes are more sensitive to ischemia than DG astrocytes. In rats subjected to transient forebrain ischemia, CA1 astrocytes lose glutamate transport activity and immunoreactivity for GFAP, S100beta, and glutamate transporter GLT-1 within a few hours of reperfusion, but without astrocyte cell death. Oxidative stress may contribute to the observed selective CA1 changes, because CA1 astrocytes show early increases in mitochondrial free radicals and reduced mitochondrial membrane potential. Similar changes were not observed in DG astrocytes. Upregulation of GLT-1 expression in astrocytes with ceftriaxone protected CA1 neurons from forebrain ischemia. We suggest that greater oxidative stress and loss of GLT-1 function selectively in CA1 astrocytes is central to the well known delayed death of CA1 neurons.
Ouyang
Yi-Bing
YB
Department of Anesthesia, Stanford University School of Medicine, Stanford, California 94305, USA.
Voloboueva
Ludmila A
LA
Xu
Li-Jun
LJ
Giffard
Rona G
RG
D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D002443:Ceftriaxone / Q000494:pharmacology; D002470:Cell Survival; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018698:Glutamic Acid / Q000493:pharmacokinetics; D006624:Hippocampus / Q000503:physiopathology*; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
D027342:Excitatory Amino Acid Transporter 2; D005904:Glial Fibrillary Acidic Protein; D018698:Glutamic Acid; D002443:Ceftriaxone