Regional Heterogeneity of Cerebral Microvessels and Brain Susceptibility to Oxidative Stress
Publication Date
December 02, 2015
Journal
PLOS ONE
Authors
Susan A. Austin, Anantha Vijay R. Santhanam, Livius V. D’uscio & Zvonimir S. Katusic
Volume
10
Issue
12
Pages
e0144062
DOI
https://dx.plos.org/10.1371/journal.pone.0144062
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0144062
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/26629821
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4668095
Europe PMC
http://europepmc.org/abstract/MED/26629821
Web of Science
000365926300153
Scopus
84956614977
Mendeley
http://www.mendeley.com/research/regional-heterogeneity-cerebral-microvessels-brain-susceptibility-oxidative-stress
Events
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Mendeley | Further Information

{"title"=>"Regional heterogeneity of cerebral microvessels and brain susceptibility to oxidative stress", "type"=>"journal", "authors"=>[{"first_name"=>"Susan A.", "last_name"=>"Austin", "scopus_author_id"=>"23099334200"}, {"first_name"=>"Anantha Vijay R.", "last_name"=>"Santhanam", "scopus_author_id"=>"12763829500"}, {"first_name"=>"Livius V.", "last_name"=>"D'Uscio", "scopus_author_id"=>"6701488280"}, {"first_name"=>"Zvonimir S.", "last_name"=>"Katusic", "scopus_author_id"=>"7006971465"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84956614977", "pui"=>"607884155", "doi"=>"10.1371/journal.pone.0144062", "isbn"=>"1932-6203", "sgr"=>"84956614977", "pmid"=>"26629821"}, "id"=>"eca4cb0a-9765-350b-8310-42facdea3128", "abstract"=>"The hippocampus is one of the earliest and most affected regions in Alzheimer's disease (AD), followed by the cortex while the cerebellum is largely spared. Importantly, endothelial dysfunction is a common feature of cerebral blood vessels in AD. In this study, we sought to determine if regional heterogeneity of cerebral microvessels might help explain the susceptibility of the hippocampus and cortex as compared to the cerebellum. We isolated microvessels from wild type mice from the cerebellum, cortex, and hippocampus to characterize their vascular phenotype. Superoxide anion was significantly higher in microvessels isolated from the cortex and hippocampus as compared to the cerebellum. Importantly, protein levels of NADPH oxidase (NOX)-2 and NOX-4 were significantly higher in the cortical and hippocampal microvessels as compared to microvessels from the cerebellum. In addition, expression of manganese superoxide dismutase protein was significantly lower in microvessels from the cortex and hippocampus as compared to cerebellum while other antioxidant enzymes were unchanged. There was no difference in eNOS protein expression between the microvessels of the three brain regions; however, bioavailability of tetrahydrobiopterin (BH4), an essential cofactor for eNOS activity, was significantly reduced in microvessels from the hippocampus and cortex as compared to the cerebellum. Higher levels of superoxide and reduced tetrahydrobiopterin bioavailability may help explain the vulnerability of the hippocampus and cortical microvessels to oxidative stress and development of endothelial dysfunction.", "link"=>"http://www.mendeley.com/research/regional-heterogeneity-cerebral-microvessels-brain-susceptibility-oxidative-stress", "reader_count"=>15, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>2, "Researcher"=>3, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Other"=>2, "Student > Bachelor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>2, "Researcher"=>3, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Other"=>2, "Student > Bachelor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>2, "Medicine and Dentistry"=>4, "Neuroscience"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Chemical Engineering"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Neuroscience"=>{"Neuroscience"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Chemical Engineering"=>{"Chemical Engineering"=>1}}, "reader_count_by_country"=>{"Canada"=>1, "Portugal"=>1, "Croatia"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2598424"], "description"=>"<p>Regional microvessels were isolated and incubated with 50 μmol/L dihydroethidium at 37° for 15 minutes. Microvessels were homogenized in methanol and intracellular superoxide anions quantified by HPLC-based fluorescence. Intracellular superoxide anions were normalized to mg protein of each sample (n = 12–13). Data are represented as mean ± SEM (P<0.05 as compared to cerebellum microvessels).</p>", "links"=>[], "tags"=>["Cerebral Microvessels", "tetrahydrobiopterin bioavailability", "brain regions", "oxidative stress", "NADPH oxidase", "bh", "Brain Susceptibility", "manganese superoxide dismutase protein", "hippocampu", "eNOS protein expression", "type mice", "protein levels", "hippocampal microvessels", "Regional Heterogeneity", "eNOS activity", "blood vessels", "antioxidant enzymes", "cerebellum", "superoxide anion", "nox", "cortex"], "article_id"=>1617294, "categories"=>["Biological Sciences"], "users"=>["Susan A. Austin", "Anantha Vijay R. Santhanam", "Livius V. d’Uscio", "Zvonimir S. Katusic"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0144062.g001", "stats"=>{"downloads"=>0, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Intracellular_superoxide_anions_are_increased_in_the_microvessels_isolated_from_the_cortex_and_hippocampus_/1617294", "title"=>"Intracellular superoxide anions are increased in the microvessels isolated from the cortex and hippocampus.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-02 04:45:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/2598426"], "description"=>"<p>(A) Brain region microvessels were isolated, homogenized, and analyzed via Western blot analyses. Membranes were probed with anti-NOX-2 (n = 7) and anti-NOX-4 (n = 7–8) antibodies. A representative image is shown. (B) Densitometric analysis of NOX-2 and (C) NOX-4 levels were perfomed and normalized against Actin as a loading control. Data are presented as mean ± SEM (P<0.05).</p>", "links"=>[], "tags"=>["Cerebral Microvessels", "tetrahydrobiopterin bioavailability", "brain regions", "oxidative stress", "NADPH oxidase", "bh", "Brain Susceptibility", "manganese superoxide dismutase protein", "hippocampu", "eNOS protein expression", "type mice", "protein levels", "hippocampal microvessels", "Regional Heterogeneity", "eNOS activity", "blood vessels", "antioxidant enzymes", "cerebellum", "superoxide anion", "nox", "cortex"], "article_id"=>1617296, "categories"=>["Biological Sciences"], "users"=>["Susan A. Austin", "Anantha Vijay R. Santhanam", "Livius V. d’Uscio", "Zvonimir S. Katusic"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0144062.g002", "stats"=>{"downloads"=>0, "page_views"=>31, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Protein_levels_of_NOX_2_and_NOX_4_were_significantly_increased_in_cortex_and_hippocampus_microvessels_/1617296", "title"=>"Protein levels of NOX-2 and NOX-4 were significantly increased in cortex and hippocampus microvessels.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-02 04:45:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/2598428"], "description"=>"<p>(A) Brain region microvessels were isolated and tissue homogenates were analyzed by Western blot analyses using anti- CuZnSOD (n = 9), ECSOD (n = 9), MnSOD (n = 10), and catalase (n = 4) antibodies. A representative image is shown. Densitometry analyses were performed normalizing against the loading control, Actin, for (B) MnSOD, (C) CuZnSOD, (D) ECSOD, and (E) catalase. Data are presented as mean ± SEM (P<0.05 as compared to cerebellum microvessels).</p>", "links"=>[], "tags"=>["Cerebral Microvessels", "tetrahydrobiopterin bioavailability", "brain regions", "oxidative stress", "NADPH oxidase", "bh", "Brain Susceptibility", "manganese superoxide dismutase protein", "hippocampu", "eNOS protein expression", "type mice", "protein levels", "hippocampal microvessels", "Regional Heterogeneity", "eNOS activity", "blood vessels", "antioxidant enzymes", "cerebellum", "superoxide anion", "nox", "cortex"], "article_id"=>1617298, "categories"=>["Biological Sciences"], "users"=>["Susan A. Austin", "Anantha Vijay R. Santhanam", "Livius V. d’Uscio", "Zvonimir S. Katusic"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0144062.g003", "stats"=>{"downloads"=>0, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Levels_of_the_antioxidant_enzyme_MnSOD_are_decreased_in_the_cortical_and_hippocampal_microvessels_/1617298", "title"=>"Levels of the antioxidant enzyme, MnSOD are decreased in the cortical and hippocampal microvessels.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-02 04:45:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/2598430"], "description"=>"<p>Biopterin levels, BH<sub>4</sub> and BH<sub>2</sub>, were analyzed by HPLC. (A) Total biopterin levels were unchanged between microvessels isolated from the three brain regions. (B) BH<sub>4</sub> levels were significantly lower in the hippocampal microvessels as compared to the cerebellum. (C) BH<sub>2</sub>, the oxidized product of BH<sub>4</sub>, was significantly higher in the cortical microvessels as compared to the cerebellum. (D) The ratio of BH<sub>4</sub>:BH<sub>2</sub>, indicative of the bioavailable levels of BH<sub>4</sub>, is significantly lower in both the cortical and hippocampal microvessels as compared to the cerebellum. Data is presented as mean ± SEM (n = 7–9, P<0.05).</p>", "links"=>[], "tags"=>["Cerebral Microvessels", "tetrahydrobiopterin bioavailability", "brain regions", "oxidative stress", "NADPH oxidase", "bh", "Brain Susceptibility", "manganese superoxide dismutase protein", "hippocampu", "eNOS protein expression", "type mice", "protein levels", "hippocampal microvessels", "Regional Heterogeneity", "eNOS activity", "blood vessels", "antioxidant enzymes", "cerebellum", "superoxide anion", "nox", "cortex"], "article_id"=>1617300, "categories"=>["Biological Sciences"], "users"=>["Susan A. Austin", "Anantha Vijay R. Santhanam", "Livius V. d’Uscio", "Zvonimir S. Katusic"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0144062.g004", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_BH_4_bioavailability_was_decreased_in_cortical_and_hippocampal_microvessels_as_compared_to_microvessels_from_the_cerebellum_/1617300", "title"=>"BH<sub>4</sub> bioavailability was decreased in cortical and hippocampal microvessels as compared to microvessels from the cerebellum.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-02 04:45:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/2598432"], "description"=>"<p>Regional microvessels were isolated and incubated with or without 30 μmol/L of L-NAME for 30 minutes at 37°. Following this incubation, microvessels were incubated with 50 μmol/L dihydroethidium at 37° for 15 minutes. Microvessels were homogenized in methanol and intracellular superoxide anions quantified by HPLC-based fluorescence. Intracellular superoxide anions were normalized to mg protein of each sample (n = 6). Data are represented as mean ± SEM.</p>", "links"=>[], "tags"=>["Cerebral Microvessels", "tetrahydrobiopterin bioavailability", "brain regions", "oxidative stress", "NADPH oxidase", "bh", "Brain Susceptibility", "manganese superoxide dismutase protein", "hippocampu", "eNOS protein expression", "type mice", "protein levels", "hippocampal microvessels", "Regional Heterogeneity", "eNOS activity", "blood vessels", "antioxidant enzymes", "cerebellum", "superoxide anion", "nox", "cortex"], "article_id"=>1617302, "categories"=>["Biological Sciences"], "users"=>["Susan A. Austin", "Anantha Vijay R. Santhanam", "Livius V. d’Uscio", "Zvonimir S. Katusic"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0144062.g005", "stats"=>{"downloads"=>0, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pre_treatment_with_L_NAME_to_inhibit_NOS_activity_did_not_significantly_alter_superoxide_anion_production_/1617302", "title"=>"Pre-treatment with L-NAME, to inhibit NOS activity, did not significantly alter superoxide anion production.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-02 04:45:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/2598434"], "description"=>"<p>(A) Isolated brain region microvessels were homogenized and analyzed by Western blot analyses using anti- eNOS (n = 11), iNOS (n = 4), and nNOS (n = 5) antibodies. A representative image is shown. Densitometry analyses were performed normalizing against Actin, a loading control, for (B) eNOS, (C) iNOS, and (D) nNOS. Data are presented as mean ± SEM.</p>", "links"=>[], "tags"=>["Cerebral Microvessels", "tetrahydrobiopterin bioavailability", "brain regions", "oxidative stress", "NADPH oxidase", "bh", "Brain Susceptibility", "manganese superoxide dismutase protein", "hippocampu", "eNOS protein expression", "type mice", "protein levels", "hippocampal microvessels", "Regional Heterogeneity", "eNOS activity", "blood vessels", "antioxidant enzymes", "cerebellum", "superoxide anion", "nox", "cortex"], "article_id"=>1617304, "categories"=>["Biological Sciences"], "users"=>["Susan A. Austin", "Anantha Vijay R. Santhanam", "Livius V. d’Uscio", "Zvonimir S. Katusic"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0144062.g006", "stats"=>{"downloads"=>0, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_NOS_protein_levels_were_not_altered_between_the_microvessels_of_the_cerebellum_cortex_or_hippocampus_/1617304", "title"=>"NOS protein levels were not altered between the microvessels of the cerebellum, cortex, or hippocampus.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-02 04:45:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/2598435"], "description"=>"<p>Regional microvessels were isolated and cGMP analyzed using a commercially available immunoassay.</p>", "links"=>[], "tags"=>["Cerebral Microvessels", "tetrahydrobiopterin bioavailability", "brain regions", "oxidative stress", "NADPH oxidase", "bh", "Brain Susceptibility", "manganese superoxide dismutase protein", "hippocampu", "eNOS protein expression", "type mice", "protein levels", "hippocampal microvessels", "Regional Heterogeneity", "eNOS activity", "blood vessels", "antioxidant enzymes", "cerebellum", "superoxide anion", "nox", "cortex"], "article_id"=>1617305, "categories"=>["Biological Sciences"], "users"=>["Susan A. Austin", "Anantha Vijay R. Santhanam", "Livius V. d’Uscio", "Zvonimir S. Katusic"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0144062.g007", "stats"=>{"downloads"=>0, "page_views"=>23, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_cGMP_levels_were_not_different_between_microvessels_isolated_from_the_cerebellum_cortex_or_hippocampus_/1617305", "title"=>"cGMP levels were not different between microvessels isolated from the cerebellum, cortex, or hippocampus.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-02 04:45:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/2598438"], "description"=>"<p>(A) Isolated brain region microvessels were homogenized and analyzed by Western blot analyses using anti- COX-1 (n = 11) and PGI2S (n = 8) antibodies. A representative image is shown. Densitometry analyses were performed normalizing against Actin, a loading control, for (B) COX-1 and (C) PGI2S. Data are presented as mean ± SEM.</p>", "links"=>[], "tags"=>["Cerebral Microvessels", "tetrahydrobiopterin bioavailability", "brain regions", "oxidative stress", "NADPH oxidase", "bh", "Brain Susceptibility", "manganese superoxide dismutase protein", "hippocampu", "eNOS protein expression", "type mice", "protein levels", "hippocampal microvessels", "Regional Heterogeneity", "eNOS activity", "blood vessels", "antioxidant enzymes", "cerebellum", "superoxide anion", "nox", "cortex"], "article_id"=>1617308, "categories"=>["Biological Sciences"], "users"=>["Susan A. Austin", "Anantha Vijay R. Santhanam", "Livius V. d’Uscio", "Zvonimir S. Katusic"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0144062.g008", "stats"=>{"downloads"=>1, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Protein_levels_of_COX_1_and_PGI_2S_did_not_differ_between_brain_region_microvessels_/1617308", "title"=>"Protein levels of COX-1 and PGI-2S did not differ between brain region microvessels.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-02 04:45:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/2598439", "https://ndownloader.figshare.com/files/2598440", "https://ndownloader.figshare.com/files/2598441", "https://ndownloader.figshare.com/files/2598442"], "description"=>"<div><p>The hippocampus is one of the earliest and most affected regions in Alzheimer’s disease (AD), followed by the cortex while the cerebellum is largely spared. Importantly, endothelial dysfunction is a common feature of cerebral blood vessels in AD. In this study, we sought to determine if regional heterogeneity of cerebral microvessels might help explain the susceptibility of the hippocampus and cortex as compared to the cerebellum. We isolated microvessels from wild type mice from the cerebellum, cortex, and hippocampus to characterize their vascular phenotype. Superoxide anion was significantly higher in microvessels isolated from the cortex and hippocampus as compared to the cerebellum. Importantly, protein levels of NADPH oxidase (NOX)-2 and NOX-4 were significantly higher in the cortical and hippocampal microvessels as compared to microvessels from the cerebellum. In addition, expression of manganese superoxide dismutase protein was significantly lower in microvessels from the cortex and hippocampus as compared to cerebellum while other antioxidant enzymes were unchanged. There was no difference in eNOS protein expression between the microvessels of the three brain regions; however, bioavailability of tetrahydrobiopterin (BH<sub>4</sub>), an essential cofactor for eNOS activity, was significantly reduced in microvessels from the hippocampus and cortex as compared to the cerebellum. Higher levels of superoxide and reduced tetrahydrobiopterin bioavailability may help explain the vulnerability of the hippocampus and cortical microvessels to oxidative stress and development of endothelial dysfunction.</p></div>", "links"=>[], "tags"=>["Cerebral Microvessels", "tetrahydrobiopterin bioavailability", "brain regions", "oxidative stress", "NADPH oxidase", "bh", "Brain Susceptibility", "manganese superoxide dismutase protein", "hippocampu", "eNOS protein expression", "type mice", "protein levels", "hippocampal microvessels", "Regional Heterogeneity", "eNOS activity", "blood vessels", "antioxidant enzymes", "cerebellum", "superoxide anion", "nox", "cortex"], "article_id"=>1617309, "categories"=>["Biological Sciences"], "users"=>["Susan A. Austin", "Anantha Vijay R. Santhanam", "Livius V. d’Uscio", "Zvonimir S. Katusic"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0144062.s001", "https://dx.doi.org/10.1371/journal.pone.0144062.s002", "https://dx.doi.org/10.1371/journal.pone.0144062.s003", "https://dx.doi.org/10.1371/journal.pone.0144062.s004"], "stats"=>{"downloads"=>5, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Regional_Heterogeneity_of_Cerebral_Microvessels_and_Brain_Susceptibility_to_Oxidative_Stress_/1617309", "title"=>"Regional Heterogeneity of Cerebral Microvessels and Brain Susceptibility to Oxidative Stress", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-12-02 04:45:32"}

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Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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