PMID- 25370861 OWN - NLM STAT- MEDLINE DCOM- 20150317 LR - 20220309 IS - 1559-7016 (Electronic) IS - 0271-678X (Print) IS - 0271-678X (Linking) VI - 35 IP - 1 DP - 2015 Jan TI - Increased BDNF protein expression after ischemic or PKC epsilon preconditioning promotes electrophysiologic changes that lead to neuroprotection. PG - 121-30 LID - 10.1038/jcbfm.2014.185 [doi] AB - Ischemic preconditioning (IPC) via protein kinase C epsilon (PKCvarepsilon) activation induces neuroprotection against lethal ischemia. Brain-derived neurotrophic factor (BDNF) is a pro-survival signaling molecule that modulates synaptic plasticity and neurogenesis. Interestingly, BDNF mRNA expression increases after IPC. In this study, we investigated whether IPC or pharmacological preconditioning (PKCvarepsilon activation) promoted BDNF-induced neuroprotection, if neuroprotection by IPC or PKCvarepsilon activation altered neuronal excitability, and whether these changes were BDNF-mediated. We used both in vitro (hippocampal organotypic cultures and cortical neuronal-glial cocultures) and in vivo (acute hippocampal slices 48 hours after preconditioning) models of IPC or PKCvarepsilon activation. BDNF protein expression increased 24 to 48 hours after preconditioning, where inhibition of the BDNF Trk receptors abolished neuroprotection against oxygen and glucose deprivation (OGD) in vitro. In addition, there was a significant decrease in neuronal firing frequency and increase in threshold potential 48 hours after preconditioning in vivo, where this threshold modulation was dependent on BDNF activation of Trk receptors in excitatory cortical neurons. In addition, 48 hours after PKCvarepsilon activation in vivo, the onset of anoxic depolarization during OGD was significantly delayed in hippocampal slices. Overall, these results suggest that after IPC or PKCvarepsilon activation, there are BDNF-dependent electrophysiologic modifications that lead to neuroprotection. FAU - Neumann, Jake T AU - Neumann JT AD - 1] Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA [2] Evelyn F. McKnight Brain Institute, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA [3] Department of Neurology, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA. FAU - Thompson, John W AU - Thompson JW AD - 1] Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA [2] Department of Neurology, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA. FAU - Raval, Ami P AU - Raval AP AD - 1] Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA [2] Evelyn F. McKnight Brain Institute, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA [3] Department of Neurology, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA. FAU - Cohan, Charles H AU - Cohan CH AD - 1] Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA [2] Evelyn F. McKnight Brain Institute, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA [3] Department of Neurology, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA [4] Neuroscience Program, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA. FAU - Koronowski, Kevin B AU - Koronowski KB AD - 1] Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA [2] Department of Neurology, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA [3] Neuroscience Program, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA. FAU - Perez-Pinzon, Miguel A AU - Perez-Pinzon MA AD - 1] Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA [2] Evelyn F. McKnight Brain Institute, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA [3] Department of Neurology, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA [4] Neuroscience Program, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA. LA - eng GR - R01 NS045676/NS/NINDS NIH HHS/United States GR - NS34773/NS/NINDS NIH HHS/United States GR - R29 NS034773/NS/NINDS NIH HHS/United States GR - R01 NS054147/NS/NINDS NIH HHS/United States GR - NS054147/NS/NINDS NIH HHS/United States GR - NS45676/NS/NINDS NIH HHS/United States GR - R01 NS034773/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20141105 PL - United States TA - J Cereb Blood Flow Metab JT - Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism JID - 8112566 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 7171WSG8A2 (BDNF protein, human) RN - EC 2.7.11.13 (Protein Kinase C-epsilon) SB - IM MH - Action Potentials/*physiology MH - Animals MH - Blotting, Western MH - Brain Ischemia/*metabolism/pathology MH - Brain-Derived Neurotrophic Factor/*biosynthesis MH - Cell Death MH - Coculture Techniques MH - Enzyme Activation MH - Female MH - Hippocampus/*metabolism/pathology MH - Humans MH - Immunohistochemistry MH - In Vitro Techniques MH - *Ischemic Preconditioning MH - Male MH - Neuroglia/pathology/physiology MH - Neuronal Plasticity/physiology MH - Neurons/pathology/physiology MH - Organ Culture Techniques MH - Protein Kinase C-epsilon/*metabolism MH - Rats, Sprague-Dawley PMC - PMC4294405 EDAT- 2014/11/06 06:00 MHDA- 2015/03/18 06:00 PMCR- 2016/01/01 CRDT- 2014/11/06 06:00 PHST- 2014/07/18 00:00 [received] PHST- 2014/10/02 00:00 [revised] PHST- 2014/10/03 00:00 [accepted] PHST- 2014/11/06 06:00 [entrez] PHST- 2014/11/06 06:00 [pubmed] PHST- 2015/03/18 06:00 [medline] PHST- 2016/01/01 00:00 [pmc-release] AID - jcbfm2014185 [pii] AID - 10.1038/jcbfm.2014.185 [doi] PST - ppublish SO - J Cereb Blood Flow Metab. 2015 Jan;35(1):121-30. doi: 10.1038/jcbfm.2014.185. Epub 2014 Nov 5.