Derangements of post-ischemic cerebral blood flow by protein kinase C delta.
Cerebral ischemia causes blood flow derangements characterized by hyperemia (increased cerebral blood flow, CBF) and subsequent hypoperfusion (decreased CBF). We previously demonstrated that protein kinase C delta (δPKC) plays an important role in hippocampal neuronal death after ischemia. However, whether part of this protection is due to the role of δPKC on CBF following cerebral ischemia remains poorly understood. We hypothesized that δPKC exacerbates hyperemia and subsequent hypoperfusion resulting in CBF derangements following ischemia. Sprague-Dawley (SD) rats pretreated with a δPKC specific inhibitor (δV1-1, 0.5 mg/kg) exhibited attenuation of hyperemia and latent hypoperfusion characterized by vasoconstriction followed by vasodilation of microvessels after 2-vessel occlusion plus hypotension measured by 2-photon microscopy. In an asphyxial cardiac arrest model (ACA), SD rats treated with δV1-1 (pre- and post-ischemia) exhibited improved perfusion after 24 h and less hippocampal CA1 neuronal death 7 days after ACA. These results suggest possible therapeutic potential of δPKC in modulating CBF and neuronal damage after cerebral ischemia.
Lin
H W
HW
Cerebral Vascular Disease Research Center, Department of Neurology, University of Miami, Miller School of Medicine, Miami, FL 33136, USA.
Defazio
R A
RA
Della-Morte
D
D
Thompson
J W
JW
Narayanan
S V
SV
Raval
A P
AP
Saul
I
I
Dave
K R
KR
Perez-Pinzon
M A
MA
D000818:Animals; D001237:Asphyxia / Q000150:complications; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology*; D002470:Cell Survival / Q000187:drug effects; D002560:Cerebrovascular Circulation; D006323:Heart Arrest / Q000209:etiology / Q000503:physiopathology; D006940:Hyperemia / Q000517:prevention & control; D008297:Male; D008833:Microcirculation; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000502:physiology*; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley
D051745:Protein Kinase C-delta
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