Document Detail


Heme oxygenase-2 modulates early pathogenesis after traumatic injury to the immature brain.
MedLine Citation:
PMID:  20389079     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We determined if heme oxygenase-2 (HO-2), an enzyme that degrades the pro-oxidant heme, confers neuroprotection in the developing brain after traumatic brain injury (TBI). Male HO-2 wild-type (WT) and homozygous knockout (KO) mice at postnatal day 21 were subjected to TBI and euthanized 1, 7, and 14 days later. Relative cerebral blood flow, measured by laser Doppler, cortical and hippocampal pathogenesis, and motor recovery were evaluated at all time points. Cerebral blood flow was found to be similar between experimental groups. Blood flow significantly decreased immediately after injury, returned to baseline by 1 day, and was significantly elevated by 7 days, post-injury. Nonheme iron preferentially accumulated in the ipsilateral cortex, hippocampus, and external capsule in both WT and KO brain-injured genotypes. There were, however, a significantly greater number of TUNEL-positive cells in the hippocampal dentate gyrus and a significantly greater cortical lesion volume in KOs relative to WTs within the first week post-injury. By 14 days post-injury, however, cortical lesion volume and cell density in the hippocampal CA3 region and dorsal thalamus were similar between the two groups. Assays of fine motor function (grip strength) over the first 2 weeks post-injury revealed a general pattern of decreased strength in the contralateral forelimbs of KOs as compared to WTs. Together, these findings demonstrate that deficiency in HO-2 alters both the kinetics of secondary damage and fine motor recovery after TBI.
Authors:
Tomoko Yoneyama-Sarnecky; Andrea D Olivas; Soraya Azari; Donna M Ferriero; Hovhannes M Manvelyan; Linda J Noble-Haeusslein
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-03-25
Journal Detail:
Title:  Developmental neuroscience     Volume:  32     ISSN:  1421-9859     ISO Abbreviation:  Dev. Neurosci.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-04-14     Completed Date:  2010-07-09     Revised Date:  2011-07-25    
Medline Journal Info:
Nlm Unique ID:  7809375     Medline TA:  Dev Neurosci     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  81-90     Citation Subset:  IM    
Copyright Information:
Copyright 2010 S. Karger AG, Basel.
Affiliation:
Department of Neurosurgery, University of California, San Francisco, Calif., USA.
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Brain Injuries / enzymology*,  pathology,  physiopathology
Cell Count
Cerebral Cortex / enzymology*,  pathology,  physiopathology
Cerebrovascular Circulation / physiology
Hand Strength / physiology
Heme Oxygenase (Decyclizing) / genetics,  metabolism*
Hippocampus / enzymology*,  pathology,  physiopathology
Immunohistochemistry
In Situ Nick-End Labeling
Laser-Doppler Flowmetry
Male
Mice
Mice, Knockout
Motor Activity / physiology
Neurons / enzymology,  pathology
Recovery of Function / physiology*
Rotarod Performance Test
Time Factors
Grant Support
ID/Acronym/Agency:
NS050159/NS/NINDS NIH HHS; R01 NS050159-03/NS/NINDS NIH HHS; R01 NS050159-04/NS/NINDS NIH HHS; R01 NS050159-05/NS/NINDS NIH HHS; R21 NS065937-01/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
EC 1.14.99.3/Heme Oxygenase (Decyclizing); EC 1.14.99.3/heme oxygenase-2
Comments/Corrections

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