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<meta name="DC.Title" content="Behavioral and Structural Effects of Single and Repeat Closed-Head Injury" />
<meta name="DC.Identifier" content="10.3174/ajnr.A6014" />
<meta name="DC.Date" content="2019-04-01" />
<meta name="DC.Publisher" content="American Journal of Neuroradiology" />
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<meta name="DC.AccessRights" content="open-access" />
<meta name="DC.Description" content="BACKGROUND AND PURPOSE: The effects of multiple head impacts, even without detectable primary injury, on subsequent behavioral impairment and structural abnormality is yet well explored. Our aim was to uncover the dynamic changes and long-term effects of single and repetitive head injury without focal contusion on tissue microstructure and macrostructure.

MATERIALS AND METHODS: We introduced a repetitive closed-head injury rodent model ( n = 70) without parenchymal lesions. We performed a longitudinal MR imaging study during a 50-day study period (T2-weighted imaging, susceptibility-weighted imaging, and diffusion tensor imaging) as well as sequential behavioral assessment. Immunohistochemical staining for astrogliosis was examined in a subgroup of animals. Paired and independent t tests were used to evaluate the outcome change after injury and the cumulative effects of impact load, respectively.

RESULTS: There was no gross morphologic evidence for head injury such as skull fracture, contusion, or hemorrhage on micro-CT and MR imaging. A significant decrease of white matter fractional anisotropy from day 21 on and an increase of gray matter fractional anisotropy from day 35 on were observed. Smaller mean cortical volume in the double-injury group was shown at day 50 compared with sham and single injury ( P &lt; .05). Behavioral deficits ( P &lt; .05) in neurologic outcome, balance, and locomotor activity were also aggravated after double injury. Histologic analysis showed astrogliosis 24 hours after injury, which persisted throughout the study period.

CONCLUSIONS: There are measurable and dynamic changes in microstructure, cortical volume, behavior, and histopathology after both single and double injury, with more severe effects seen after double injury. This work bridges cross-sectional evidence from human subject and pathologic studies using animal models with a multi-time point, longitudinal research paradigm.

AD
:   axial diffusivity
CD 68
:   Cluster of Differentiation 68
CHI
:   closed-head injury
FA
:   fractional anisotropy
GFAP
:   glial fibrillary acidic protein
MD
:   mean diffusivity
mNSS
:   modified Neurological Severity Score
RD
:   radial diffusivity
TBI
:   traumatic brain injury" />
<meta name="DC.Contributor" content="Y.-C.J. Kao" />
<meta name="DC.Contributor" content="Y.W. Lui" />
<meta name="DC.Contributor" content="C.-F. Lu" />
<meta name="DC.Contributor" content="H.-L. Chen" />
<meta name="DC.Contributor" content="B.-Y. Hsieh" />
<meta name="DC.Contributor" content="C.-Y. Chen" />
<meta name="article:published_time" content="2019-04-01" />
<meta name="article:section" content="Adult Brain" />
<meta name="citation_title" content="Behavioral and Structural Effects of Single and Repeat Closed-Head Injury" />
<meta name="citation_abstract" lang="en" content="&lt;h3&gt;BACKGROUND AND PURPOSE:&lt;/h3&gt;
&lt;p&gt;The effects of multiple head impacts, even without detectable primary injury, on subsequent behavioral impairment and structural abnormality is yet well explored. Our aim was to uncover the dynamic changes and long-term effects of single and repetitive head injury without focal contusion on tissue microstructure and macrostructure.&lt;/p&gt;&lt;h3&gt;MATERIALS AND METHODS:&lt;/h3&gt;
&lt;p&gt;We introduced a repetitive closed-head injury rodent model (&lt;i&gt;n&lt;/i&gt; = 70) without parenchymal lesions. We performed a longitudinal MR imaging study during a 50-day study period (T&lt;sub&gt;2&lt;/sub&gt;-weighted imaging, susceptibility-weighted imaging, and diffusion tensor imaging) as well as sequential behavioral assessment. Immunohistochemical staining for astrogliosis was examined in a subgroup of animals. Paired and independent &lt;i&gt;t&lt;/i&gt; tests were used to evaluate the outcome change after injury and the cumulative effects of impact load, respectively.&lt;/p&gt;&lt;h3&gt;RESULTS:&lt;/h3&gt;
&lt;p&gt;There was no gross morphologic evidence for head injury such as skull fracture, contusion, or hemorrhage on micro-CT and MR imaging. A significant decrease of white matter fractional anisotropy from day 21 on and an increase of gray matter fractional anisotropy from day 35 on were observed. Smaller mean cortical volume in the double-injury group was shown at day 50 compared with sham and single injury (&lt;i&gt;P&lt;/i&gt; &amp;lt; .05). Behavioral deficits (&lt;i&gt;P&lt;/i&gt; &amp;lt; .05) in neurologic outcome, balance, and locomotor activity were also aggravated after double injury. Histologic analysis showed astrogliosis 24 hours after injury, which persisted throughout the study period.&lt;/p&gt;&lt;h3&gt;CONCLUSIONS:&lt;/h3&gt;
&lt;p&gt;There are measurable and dynamic changes in microstructure, cortical volume, behavior, and histopathology after both single and double injury, with more severe effects seen after double injury. This work bridges cross-sectional evidence from human subject and pathologic studies using animal models with a multi-time point, longitudinal research paradigm.&lt;/p&gt;" />
<meta name="citation_journal_title" content="American Journal of Neuroradiology" />
<meta name="citation_publisher" content="American Journal of Neuroradiology" />
<meta name="citation_publication_date" content="2019/04/01" />
<meta name="citation_mjid" content="ajnr;40/4/601" />
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<meta name="citation_issn" content="0195-6108" />
<meta name="citation_issn" content="1936-959X" />
<meta name="citation_doi" content="10.3174/ajnr.A6014" />
<meta name="citation_pmid" content="30923084" />
<meta name="citation_volume" content="40" />
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<meta name="citation_article_type" content="Research Article" />
<meta name="citation_section" content="Adult Brain" />
<meta name="citation_firstpage" content="601" />
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<meta name="citation_author" content="Y.-C.J. Kao" />
<meta name="citation_author_institution" content="aFrom the Neuroscience Research Center (Y.-C.J.K., C.-Y.C.)" />
<meta name="citation_author_institution" content="bTranslational Imaging Research Center (Y.-C.J.K., C.-Y.C.), Taipei Medical University, Taipei, Taiwan" />
<meta name="citation_author_institution" content="cDepartment of Radiology (Y.-C.J.K., C.-Y.C.), School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan" />
<meta name="citation_author_institution" content="hRadiogenomic Research Center (Y.-C.J.K., C.-Y.C.), Taipei Medical University Hospital, Taipei, Taiwan" />
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<meta name="citation_author" content="Y.W. Lui" />
<meta name="citation_author_institution" content="dDepartment of Radiology (Y.W.L.), NYU School of Medicine/NYU Langone Health, New York, New York" />
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<meta name="citation_author" content="C.-F. Lu" />
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<meta name="citation_author" content="H.-L. Chen" />
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<meta name="citation_author_orcid" content="https://orcid.org/0000-0002-5313-3072" />
<meta name="citation_author" content="B.-Y. Hsieh" />
<meta name="citation_author_institution" content="iDepartment of Biomedical Imaging and Radiological Science (B.-Y.H.), China Medical University, Taichung, Taiwan." />
<meta name="citation_author_orcid" content="https://orcid.org/0000-0002-9379-4211" />
<meta name="citation_author" content="C.-Y. Chen" />
<meta name="citation_author_institution" content="aFrom the Neuroscience Research Center (Y.-C.J.K., C.-Y.C.)" />
<meta name="citation_author_institution" content="bTranslational Imaging Research Center (Y.-C.J.K., C.-Y.C.), Taipei Medical University, Taipei, Taiwan" />
<meta name="citation_author_institution" content="cDepartment of Radiology (Y.-C.J.K., C.-Y.C.), School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan" />
<meta name="citation_author_institution" content="gMedical Imaging (C.-Y.C.)" />
<meta name="citation_author_institution" content="hRadiogenomic Research Center (Y.-C.J.K., C.-Y.C.), Taipei Medical University Hospital, Taipei, Taiwan" />
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<meta name="twitter:title" content="Behavioral and Structural Effects of Single and Repeat Closed-Head Injury" />
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<meta name="twitter:description" content="BACKGROUND AND PURPOSE: The effects of multiple head impacts, even without detectable primary injury, on subsequent behavioral impairment and structural abnormality is yet well explored. Our aim was to uncover the dynamic changes and long-term effects of single and repetitive head injury without focal contusion on tissue microstructure and macrostructure.

MATERIALS AND METHODS: We introduced a repetitive closed-head injury rodent model ( n = 70) without parenchymal lesions. We performed a longitudinal MR imaging study during a 50-day study period (T2-weighted imaging, susceptibility-weighted imaging, and diffusion tensor imaging) as well as sequential behavioral assessment. Immunohistochemical staining for astrogliosis was examined in a subgroup of animals. Paired and independent t tests were used to evaluate the outcome change after injury and the cumulative effects of impact load, respectively.

RESULTS: There was no gross morphologic evidence for head injury such as skull fracture, contusion, or hemorrhage on micro-CT and MR imaging. A significant decrease of white matter fractional anisotropy from day 21 on and an increase of gray matter fractional anisotropy from day 35 on were observed. Smaller mean cortical volume in the double-injury group was shown at day 50 compared with sham and single injury ( P &lt; .05). Behavioral deficits ( P &lt; .05) in neurologic outcome, balance, and locomotor activity were also aggravated after double injury. Histologic analysis showed astrogliosis 24 hours after injury, which persisted throughout the study period.

CONCLUSIONS: There are measurable and dynamic changes in microstructure, cortical volume, behavior, and histopathology after both single and double injury, with more severe effects seen after double injury. This work bridges cross-sectional evidence from human subject and pathologic studies using animal models with a multi-time point, longitudinal research paradigm.

AD
:   axial diffusivity
CD 68
:   Cluster of Differentiation 68
CHI
:   closed-head injury
FA
:   fractional anisotropy
GFAP
:   glial fibrillary acidic protein
MD
:   mean diffusivity
mNSS
:   modified Neurological Severity Score
RD
:   radial diffusivity
TBI
:   traumatic brain injury" />
<meta name="og-title" property="og:title" content="Behavioral and Structural Effects of Single and Repeat Closed-Head Injury" />
<meta name="og-url" property="og:url" content="http://ajnr-stage2.stage.highwire.org/content/40/4/601" />
<meta name="og-site-name" property="og:site_name" content="American Journal of Neuroradiology" />
<meta name="og-description" property="og:description" content="BACKGROUND AND PURPOSE: The effects of multiple head impacts, even without detectable primary injury, on subsequent behavioral impairment and structural abnormality is yet well explored. Our aim was to uncover the dynamic changes and long-term effects of single and repetitive head injury without focal contusion on tissue microstructure and macrostructure.

MATERIALS AND METHODS: We introduced a repetitive closed-head injury rodent model ( n = 70) without parenchymal lesions. We performed a longitudinal MR imaging study during a 50-day study period (T2-weighted imaging, susceptibility-weighted imaging, and diffusion tensor imaging) as well as sequential behavioral assessment. Immunohistochemical staining for astrogliosis was examined in a subgroup of animals. Paired and independent t tests were used to evaluate the outcome change after injury and the cumulative effects of impact load, respectively.

RESULTS: There was no gross morphologic evidence for head injury such as skull fracture, contusion, or hemorrhage on micro-CT and MR imaging. A significant decrease of white matter fractional anisotropy from day 21 on and an increase of gray matter fractional anisotropy from day 35 on were observed. Smaller mean cortical volume in the double-injury group was shown at day 50 compared with sham and single injury ( P &lt; .05). Behavioral deficits ( P &lt; .05) in neurologic outcome, balance, and locomotor activity were also aggravated after double injury. Histologic analysis showed astrogliosis 24 hours after injury, which persisted throughout the study period.

CONCLUSIONS: There are measurable and dynamic changes in microstructure, cortical volume, behavior, and histopathology after both single and double injury, with more severe effects seen after double injury. This work bridges cross-sectional evidence from human subject and pathologic studies using animal models with a multi-time point, longitudinal research paradigm.

AD
:   axial diffusivity
CD 68
:   Cluster of Differentiation 68
CHI
:   closed-head injury
FA
:   fractional anisotropy
GFAP
:   glial fibrillary acidic protein
MD
:   mean diffusivity
mNSS
:   modified Neurological Severity Score
RD
:   radial diffusivity
TBI
:   traumatic brain injury" />
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    <div class="highwire-article-citation highwire-citation-type-highwire-article node66941--5" data-node-nid="66941" id="top-node-66941--6598104333" data-pisa="ajnr;40/4/601" data-pisa-master="ajnr;ajnr.A6014" data-apath="/ajnr/40/4/601.atom" data-hw-author-tooltip-instance="highwire_author_tooltip"><div class="highwire-cite highwire-cite-highwire-article highwire-citation-jcore-article-title-complete clearfix has-author-tooltip highwire-citation-highwire-article-top-a">
  
  
      <div class="highwire-cite-overline"><span  class="highwire-cite-metadata-article-type highwire-cite-metadata">Research Article</span><span class="separator-pipe"></span><span  class="highwire-cite-metadata-art-cat highwire-cite-metadata"><span class="wrapper">Adult Brain</span></span></div>
  
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      <h1 class="highwire-cite-title" id="page-title">Behavioral and Structural Effects of Single and Repeat Closed-Head Injury</h1>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">Y.-C.J. Kao</span>, <span class="highwire-citation-author" data-delta="1">Y.W. Lui</span>, <span class="highwire-citation-author" data-delta="2">C.-F. Lu</span>, <span class="highwire-citation-author" data-delta="3">H.-L. Chen</span>, <span class="highwire-citation-author" data-delta="4">B.-Y. Hsieh</span> and <span class="highwire-citation-author" data-delta="5">C.-Y. Chen</span></span></div>
  
    	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-journal highwire-cite-metadata">American Journal of Neuroradiology </span><span  class="highwire-cite-metadata-date highwire-cite-metadata">April 2019,  </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">40 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(4) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">601-608; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.3174/ajnr.A6014 </span></div>
  
  
  
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<div id="hw-article-author-popups-top-node-66941--6598104333" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">Y.-C.J. Kao </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Neuroscience Research Center (Y.-C.J.K., C.-Y.C.)</div><div class='author-affiliation'><span class='nlm-sup'>b</span>Translational Imaging Research Center (Y.-C.J.K., C.-Y.C.), Taipei Medical University, Taipei, Taiwan</div><div class='author-affiliation'><span class='nlm-sup'>c</span>Department of Radiology (Y.-C.J.K., C.-Y.C.), School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan</div><div class='author-affiliation'><span class='nlm-sup'>h</span>Radiogenomic Research Center (Y.-C.J.K., C.-Y.C.), Taipei Medical University Hospital, Taipei, Taiwan</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=Y.-C.J.%2BKao%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Kao%20Y&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AY.-C.J.%2BKao%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="https://orcid.org/0000-0001-7416-759X" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Y.-C.J. Kao</a></li></ul></div><div class="author-tooltip-1"><div class="author-tooltip-name">Y.W. Lui </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>d</span>Department of Radiology (Y.W.L.), NYU School of Medicine/NYU Langone Health, New York, New York</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=Y.W.%2BLui%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Lui%20Y&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AY.W.%2BLui%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="https://orcid.org/0000-0002-9984-9164" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Y.W. Lui</a></li></ul></div><div class="author-tooltip-2"><div class="author-tooltip-name">C.-F. Lu </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>e</span>Department of Biomedical Imaging and Radiological Sciences (C.-F.L.), National Yang-Ming University, Taipei, Taiwan</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=C.-F.%2BLu%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Lu%20C&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AC.-F.%2BLu%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="https://orcid.org/0000-0003-1344-9950" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for C.-F. Lu</a></li></ul></div><div class="author-tooltip-3"><div class="author-tooltip-name">H.-L. Chen </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>f</span>Departments of Medical Research (H.-L.C.)</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=H.-L.%2BChen%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Chen%20H&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AH.-L.%2BChen%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="https://orcid.org/0000-0002-5313-3072" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for H.-L. Chen</a></li></ul></div><div class="author-tooltip-4"><div class="author-tooltip-name">B.-Y. Hsieh </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>i</span>Department of Biomedical Imaging and Radiological Science (B.-Y.H.), China Medical University, Taichung, Taiwan.</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=B.-Y.%2BHsieh%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Hsieh%20B&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AB.-Y.%2BHsieh%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="https://orcid.org/0000-0002-9379-4211" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for B.-Y. Hsieh</a></li></ul></div><div class="author-tooltip-5"><div class="author-tooltip-name">C.-Y. Chen </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Neuroscience Research Center (Y.-C.J.K., C.-Y.C.)</div><div class='author-affiliation'><span class='nlm-sup'>b</span>Translational Imaging Research Center (Y.-C.J.K., C.-Y.C.), Taipei Medical University, Taipei, Taiwan</div><div class='author-affiliation'><span class='nlm-sup'>c</span>Department of Radiology (Y.-C.J.K., C.-Y.C.), School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan</div><div class='author-affiliation'><span class='nlm-sup'>g</span>Medical Imaging (C.-Y.C.)</div><div class='author-affiliation'><span class='nlm-sup'>h</span>Radiogenomic Research Center (Y.-C.J.K., C.-Y.C.), Taipei Medical University Hospital, Taipei, Taiwan</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=C.-Y.%2BChen%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Chen%20C&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AC.-Y.%2BChen%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="https://orcid.org/0000-0003-0428-4373" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for C.-Y. 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    <div class="highwire-markup"><div xmlns="http://www.w3.org/1999/xhtml" data-highwire-cite-ref-tooltip-instance="highwire_reflinks_tooltip" class="content-block-markup" xmlns:xhtml="http://www.w3.org/1999/xhtml"><div class="article abstract-view "><span class="highwire-journal-article-marker-start"></span><div class="section abstract" id="abstract-1"><h2>Abstract</h2><div id="sec-1" class="subsection"><p id="p-2"><strong>BACKGROUND AND PURPOSE:</strong> The effects of multiple head impacts, even without detectable primary injury, on subsequent behavioral impairment and structural abnormality is yet well explored. Our aim was to uncover the dynamic changes and long-term effects of single and repetitive head injury without focal contusion on tissue microstructure and macrostructure.</p></div><div id="sec-2" class="subsection"><p id="p-3"><strong>MATERIALS AND METHODS:</strong> We introduced a repetitive closed-head injury rodent model (<em>n</em> = 70) without parenchymal lesions. We performed a longitudinal MR imaging study during a 50-day study period (T<sub>2</sub>-weighted imaging, susceptibility-weighted imaging, and diffusion tensor imaging) as well as sequential behavioral assessment. Immunohistochemical staining for astrogliosis was examined in a subgroup of animals. Paired and independent <em>t</em> tests were used to evaluate the outcome change after injury and the cumulative effects of impact load, respectively.</p></div><div id="sec-3" class="subsection"><p id="p-4"><strong>RESULTS:</strong> There was no gross morphologic evidence for head injury such as skull fracture, contusion, or hemorrhage on micro-CT and MR imaging. A significant decrease of white matter fractional anisotropy from day 21 on and an increase of gray matter fractional anisotropy from day 35 on were observed. Smaller mean cortical volume in the double-injury group was shown at day 50 compared with sham and single injury (<em>P</em> &lt; .05). Behavioral deficits (<em>P</em> &lt; .05) in neurologic outcome, balance, and locomotor activity were also aggravated after double injury. Histologic analysis showed astrogliosis 24 hours after injury, which persisted throughout the study period.</p></div><div id="sec-4" class="subsection"><p id="p-5"><strong>CONCLUSIONS:</strong> There are measurable and dynamic changes in microstructure, cortical volume, behavior, and histopathology after both single and double injury, with more severe effects seen after double injury. This work bridges cross-sectional evidence from human subject and pathologic studies using animal models with a multi-time point, longitudinal research paradigm.</p></div></div><div class="section glossary" id="glossary-1"><h2 class="">ABBREVIATIONS:</h2><dl id="def-list-1"><dt id="def-item-1">AD<span class="def-item-dt-sep"></span></dt><dd>axial diffusivity<span class="def-item-dd-sep"></span></dd><dt id="def-item-2">CD 68<span class="def-item-dt-sep"></span></dt><dd>Cluster of Differentiation 68<span class="def-item-dd-sep"></span></dd><dt id="def-item-3">CHI<span class="def-item-dt-sep"></span></dt><dd>closed-head injury<span class="def-item-dd-sep"></span></dd><dt id="def-item-4">FA<span class="def-item-dt-sep"></span></dt><dd>fractional anisotropy<span class="def-item-dd-sep"></span></dd><dt id="def-item-5">GFAP<span class="def-item-dt-sep"></span></dt><dd>glial fibrillary acidic protein<span class="def-item-dd-sep"></span></dd><dt id="def-item-6">MD<span class="def-item-dt-sep"></span></dt><dd>mean diffusivity<span class="def-item-dd-sep"></span></dd><dt id="def-item-7">mNSS<span class="def-item-dt-sep"></span></dt><dd>modified Neurological Severity Score<span class="def-item-dd-sep"></span></dd><dt id="def-item-8">RD<span class="def-item-dt-sep"></span></dt><dd>radial diffusivity<span class="def-item-dd-sep"></span></dd><dt id="def-item-9">TBI<span class="def-item-dt-sep"></span></dt><dd>traumatic brain injury</dd></dl></div><ul class="copyright-statement"><li class="fn" id="copyright-statement-1">© 2019 by American Journal of Neuroradiology</li></ul><div class="license" id="license-1"><p id="p-1">Indicates open access to non-subscribers at <a href="http://www.ajnr.org" rel="license">www.ajnr.org</a></p></div><span class="highwire-journal-article-marker-end"></span></div><span class="related-urls"></span></div><a href="http://ajnr-stage2.stage.highwire.org/content/40/4/601.full" class="hw-link hw-link-article-full-text" data-icon-position="" data-hide-link-title="0">View Full Text</a></div>  </div>

  
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        	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-volume highwire-cite-metadata">Vol. 40</span>, <span  class="highwire-cite-metadata-issue highwire-cite-metadata">Issue 4 </span><div  class="highwire-cite-metadata-pubdate highwire-cite-metadata">1 Apr 2019 </div></div>
      
      
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    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">Y.-C.J.</span> <span class="nlm-surname">Kao</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">Y.W.</span> <span class="nlm-surname">Lui</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">C.-F.</span> <span class="nlm-surname">Lu</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">H.-L.</span> <span class="nlm-surname">Chen</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">B.-Y.</span> <span class="nlm-surname">Hsieh</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">C.-Y.</span> <span class="nlm-surname">Chen</span></span></span></div>
  
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