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Integrity of Cerebellar Fastigial Nucleus Intrinsic Neurons Is Critical for the Global Ischemic Preconditioning

Excitation of intrinsic neurons of cerebellar fastigial nucleus (FN) renders brain tolerant to local and global ischemia. This effect reaches a maximum 72 h after the stimulation and lasts over 10 days. Comparable neuroprotection is observed following sublethal global brain ischemia, a phenomenon kn...

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Autores principales: Golanov, Eugene V., Regnier-Golanov, Angelique S., Britz, Gavin W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664048/
https://www.ncbi.nlm.nih.gov/pubmed/28934119
http://dx.doi.org/10.3390/brainsci7100121
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author Golanov, Eugene V.
Regnier-Golanov, Angelique S.
Britz, Gavin W.
author_facet Golanov, Eugene V.
Regnier-Golanov, Angelique S.
Britz, Gavin W.
author_sort Golanov, Eugene V.
collection PubMed
description Excitation of intrinsic neurons of cerebellar fastigial nucleus (FN) renders brain tolerant to local and global ischemia. This effect reaches a maximum 72 h after the stimulation and lasts over 10 days. Comparable neuroprotection is observed following sublethal global brain ischemia, a phenomenon known as preconditioning. We hypothesized that FN may participate in the mechanisms of ischemic preconditioning as a part of the intrinsic neuroprotective mechanism. To explore potential significance of FN neurons in brain ischemic tolerance we lesioned intrinsic FN neurons with excitotoxin ibotenic acid five days before exposure to 20 min four-vessel occlusion (4-VO) global ischemia while analyzing neuronal damage in Cornu Ammoni area 1 (CA1) hippocampal area one week later. In FN-lesioned animals, loss of CA1 cells was higher by 22% compared to control (phosphate buffered saline (PBS)-injected) animals. Moreover, lesion of FN neurons increased morbidity following global ischemia by 50%. Ablation of FN neurons also reversed salvaging effects of five-minute ischemic preconditioning on CA1 neurons and morbidity, while ablation of cerebellar dentate nucleus neurons did not change effect of ischemic preconditioning. We conclude that FN is an important part of intrinsic neuroprotective system, which participates in ischemic preconditioning and may participate in naturally occurring neuroprotection, such as “diving response”.
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spelling pubmed-56640482017-11-06 Integrity of Cerebellar Fastigial Nucleus Intrinsic Neurons Is Critical for the Global Ischemic Preconditioning Golanov, Eugene V. Regnier-Golanov, Angelique S. Britz, Gavin W. Brain Sci Article Excitation of intrinsic neurons of cerebellar fastigial nucleus (FN) renders brain tolerant to local and global ischemia. This effect reaches a maximum 72 h after the stimulation and lasts over 10 days. Comparable neuroprotection is observed following sublethal global brain ischemia, a phenomenon known as preconditioning. We hypothesized that FN may participate in the mechanisms of ischemic preconditioning as a part of the intrinsic neuroprotective mechanism. To explore potential significance of FN neurons in brain ischemic tolerance we lesioned intrinsic FN neurons with excitotoxin ibotenic acid five days before exposure to 20 min four-vessel occlusion (4-VO) global ischemia while analyzing neuronal damage in Cornu Ammoni area 1 (CA1) hippocampal area one week later. In FN-lesioned animals, loss of CA1 cells was higher by 22% compared to control (phosphate buffered saline (PBS)-injected) animals. Moreover, lesion of FN neurons increased morbidity following global ischemia by 50%. Ablation of FN neurons also reversed salvaging effects of five-minute ischemic preconditioning on CA1 neurons and morbidity, while ablation of cerebellar dentate nucleus neurons did not change effect of ischemic preconditioning. We conclude that FN is an important part of intrinsic neuroprotective system, which participates in ischemic preconditioning and may participate in naturally occurring neuroprotection, such as “diving response”. MDPI 2017-09-21 /pmc/articles/PMC5664048/ /pubmed/28934119 http://dx.doi.org/10.3390/brainsci7100121 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Golanov, Eugene V.
Regnier-Golanov, Angelique S.
Britz, Gavin W.
Integrity of Cerebellar Fastigial Nucleus Intrinsic Neurons Is Critical for the Global Ischemic Preconditioning
title Integrity of Cerebellar Fastigial Nucleus Intrinsic Neurons Is Critical for the Global Ischemic Preconditioning
title_full Integrity of Cerebellar Fastigial Nucleus Intrinsic Neurons Is Critical for the Global Ischemic Preconditioning
title_fullStr Integrity of Cerebellar Fastigial Nucleus Intrinsic Neurons Is Critical for the Global Ischemic Preconditioning
title_full_unstemmed Integrity of Cerebellar Fastigial Nucleus Intrinsic Neurons Is Critical for the Global Ischemic Preconditioning
title_short Integrity of Cerebellar Fastigial Nucleus Intrinsic Neurons Is Critical for the Global Ischemic Preconditioning
title_sort integrity of cerebellar fastigial nucleus intrinsic neurons is critical for the global ischemic preconditioning
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664048/
https://www.ncbi.nlm.nih.gov/pubmed/28934119
http://dx.doi.org/10.3390/brainsci7100121
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