| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Physiology and Pediatrics, Vascular Biology Center, University of Tennessee Health Science Center, Memphis, TN, USA
* To whom correspondence should be addressed. E-mail: hparf{at}physio1.utmem.edu.
The extended postictal state is characterized by neurological problems in patients. Inadequate blood supply to the brain and impaired cerebral autoregulation may contribute to seizure-induced neuronal damage. Recent evidence in newborn pigs indicates that activation of the anti-oxidative enzyme, heme oxygenase (HO), at the onset of seizures is necessary for increased cerebral blood flow during the ictal episode and for normal cerebral vascular functioning during the immediate postictal period. We hypothesized that seizures cause prolonged postictal cerebral vascular dysfunction that can be accentuated by HO inhibition and rescued by HO overexpression. Cerebral vascular responses to endothelium-dependent (hypercapnia, bradykinin) and endothelium-independent (isoproterenol, sodium nitroprusside) stimuli were assessed 48 h after bicuculline-induced seizures in: a) saline-control newborn piglets, b) HO-inhibited animals (HO was inhibited by tin protoporphyrin, SnPP, 3 mg/kg i.v.), and c) HO-overexpressing piglets (HO-1 was upregulated by cobalt protoporphyrin, CoPP, 50 mg/kg i.p.) Extended alterations of HO expression in cerebral microvessels were confirmed by measuring CO production and HO-1/HO-2 proteins. Our data provide evidence that seizures cause a severe, sustained, postictal cerebral vascular dysfunction as reflected by impaired vascular reactivity to physiologically relevant dilators. During the delayed postictal state, vascular reactivity to all dilator stimuli was reduced in saline-control and, to a greater extent, in HO-inhibited animals. In CoPP-treated piglets, no reduction in postictal cerebral vascular reactivity was observed. These findings may indicate that CoPP prevents postictal cerebral vascular dysfunction by upregulating HO-1, a finding that might have implications for preventing postictal neurological complications.
This article has been cited by other articles:
|
|
 |
|
  J. Sunderram, J. Semmlow, S. Thakker-Varia, M. Bhaumik, O. Hoang-Le, and J. A. Neubauer Heme oxygenase-1-dependent central cardiorespiratory adaptations to chronic hypoxia in mice Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2009; 297(2): R300 - R312. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zimmermann, C. W. Leffler, D. Tcheranova, A. L. Fedinec, and H. Parfenova Cerebroprotective effects of the CO-releasing molecule CORM-A1 against seizure-induced neonatal vascular injury Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2501 - H2507. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Basuroy, S. Bhattacharya, D. Tcheranova, Y. Qu, R. F. Regan, C. W. Leffler, and H. Parfenova HO-2 provides endogenous protection against oxidative stress and apoptosis caused by TNF-{alpha} in cerebral vascular endothelial cells Am J Physiol Cell Physiol, November 1, 2006; 291(5): C897 - C908. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Parfenova, S. Basuroy, S. Bhattacharya, D. Tcheranova, Y. Qu, R. F. Regan, and C. W. Leffler Glutamate induces oxidative stress and apoptosis in cerebral vascular endothelial cells: contributions of HO-1 and HO-2 to cytoprotection Am J Physiol Cell Physiol, May 1, 2006; 290(5): C1399 - C1410. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. W. Leffler, H. Parfenova, J. H. Jaggar, and R. Wang Carbon monoxide and hydrogen sulfide: gaseous messengers in cerebrovascular circulation J Appl Physiol, March 1, 2006; 100(3): 1065 - 1076. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
