Contributions of astrocytes and CO to pial arteriolar dilation to glutamate in newborn pigs

Charles Leffler, Elena Parfenova, Alexander L. Fedinec, Shyamali Basuroy, Dilyara Tcheranova

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Astrocytes can act as intermediaries between neurons and cerebral arterioles to regulate vascular tone in response to neuronal activity. Release of glutamate from presynaptic neurons increases blood flow to match metabolic demands. CO is a gasotransmitter that can be related to neural function and blood flow regulation in the brain. The present study addresses the hypothesis that glutamatergic stimulation promotes perivascular astrocyte CO production and pial arteriolar dilation in the newborn brain. Experiments used anesthetized newborn pigs with closed cranial windows, piglet astrocytes, and cerebrovascular endothelial cells in primary culture and immunocytochemical visualization of astrocytic markers. Pial arterioles and arteries of newborn pigs are ensheathed by astrocytes visualized by glial fibrillary acidic protein staining. Treatment (2 h) of astrocytes in culture with L-2-α-aminoadipic acid (L-AAA), followed by 14 h in toxin free medium, dose-dependently increased cell detachment, suggesting injury. Conversely, 16 h of continuous exposure to L-AAA caused no decrease in endothelial cell attachment. In vivo, topical L-AAA (2 mM, 5 h) disrupted the cortical glia limitans histologically. Such treatment also eliminated pial arteriolar dilation to the astrocyte-dependent dilator ADP and to glutamate but not to isoproterenol or CO. Glutamate stimulated CO production by the brain surface that also was abolished following L-AAA. In contrast, tetrodotoxin blocked dilation to N-methyl-D-aspartate but not to glutamate, isoproterenol, or CO or the glutamate-induced increase in CO. The concurrent loss of CO production and pial arteriolar dilation to glutamate following astrocyte injury suggests astrocytes may employ CO as a gasotransmitter for glutamatergic cerebrovascular dilation.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume291
Issue number6
DOIs
StatePublished - Dec 18 2006

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Carbon Monoxide
Astrocytes
Dilatation
Glutamic Acid
2-Aminoadipic Acid
Swine
Gasotransmitters
Arterioles
Isoproterenol
Brain
Endothelial Cells
Neurons
Glial Fibrillary Acidic Protein
Tetrodotoxin
Wounds and Injuries
N-Methylaspartate
Neuroglia
Adenosine Diphosphate
Blood Vessels
Arteries

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Contributions of astrocytes and CO to pial arteriolar dilation to glutamate in newborn pigs. / Leffler, Charles; Parfenova, Elena; Fedinec, Alexander L.; Basuroy, Shyamali; Tcheranova, Dilyara.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 291, No. 6, 18.12.2006.

Research output: Contribution to journalArticle

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