TY - CHAP
T1 - Differential effects of delta and epsilon protein kinase C in modulation of postischemic cerebral blood flow
AU - Lin, Hung Wen
AU - Della-Morte, David
AU - Thompson, John W.
AU - Gresia, Victoria L.
AU - Narayanan, Srinivasan V.
AU - Defazio, R. Anthony
AU - Raval, Ami P.
AU - Saul, Isabel
AU - Dave, Kunjan R.
AU - Morris, Kahlilia C.
AU - Si, Min Liang
AU - Perez-Pinzon, Miguel A.
PY - 2012
Y1 - 2012
N2 - Cerebral ischemia causes cerebral blood flow (CBF) derangements resulting in neuronal damage by enhanced protein kinase C delta (δPKC) levels leading to hippocampal and cortical neuronal death after ischemia. Contrarily, activation of εPKC mediates ischemic tolerance by decreasing vascular tone providing neuroprotection. However, whether part of this protection is due to the role of differential isozymes of PKCs on CBF following cerebral ischemia remains poorly understood. 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 two-vessel occlusion plus hypotension. In an asphyxial cardiac arrest (ACA) model, rats treated with δV1-1 (pre- and postischemia) exhibited improved perfusion after 24 h and less hippocampal CA1 and cortical neuronal death 7 days after ACA. On the contrary, εPKC-selective peptide activator, conferred neuroprotection in the CA1 region of the rat hippocampus 30 min before induction of global cerebral ischemia and decreased regional CBF during the reperfusion phase. These opposing effects of δv. εPKC suggest a possible therapeutic potential by modulating CBF preventing neuronal damage after cerebral ischemia.
AB - Cerebral ischemia causes cerebral blood flow (CBF) derangements resulting in neuronal damage by enhanced protein kinase C delta (δPKC) levels leading to hippocampal and cortical neuronal death after ischemia. Contrarily, activation of εPKC mediates ischemic tolerance by decreasing vascular tone providing neuroprotection. However, whether part of this protection is due to the role of differential isozymes of PKCs on CBF following cerebral ischemia remains poorly understood. 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 two-vessel occlusion plus hypotension. In an asphyxial cardiac arrest (ACA) model, rats treated with δV1-1 (pre- and postischemia) exhibited improved perfusion after 24 h and less hippocampal CA1 and cortical neuronal death 7 days after ACA. On the contrary, εPKC-selective peptide activator, conferred neuroprotection in the CA1 region of the rat hippocampus 30 min before induction of global cerebral ischemia and decreased regional CBF during the reperfusion phase. These opposing effects of δv. εPKC suggest a possible therapeutic potential by modulating CBF preventing neuronal damage after cerebral ischemia.
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U2 - 10.1007/978-1-4614-1566-4_10
DO - 10.1007/978-1-4614-1566-4_10
M3 - Chapter
C2 - 22259083
AN - SCOPUS:84863045578
SN - 9781461415657
VL - 737
T3 - Advances in Experimental Medicine and Biology
SP - 63
EP - 69
BT - Advances in Experimental Medicine and Biology
ER -