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Article: Mild hypoxic-ischemic injury in the neonatal rat brain: Longitudinal evaluation of white matter using diffusion tensor MR imaging

TitleMild hypoxic-ischemic injury in the neonatal rat brain: Longitudinal evaluation of white matter using diffusion tensor MR imaging
Authors
Issue Date2009
PublisherAmerican Society of Neuroradiology. The Journal's web site is located at http://www.ajnr.org
Citation
American Journal Of Neuroradiology, 2009, v. 30 n. 10, p. 1907-1913 How to Cite?
AbstractBACKGROUND AND PURPOSE: Selective white matter (WM) damage is a known sequela of mild hypoxic-ischemic (HI) injury in the neonatal rat model. The aim of this study was to evaluate longitudinally mild HI-induced WM damage (represented by the external capsule [EC]) by diffusion tensor MR imaging (DTI) and to correlate the findings with histology. MATERIALS AND METHODS: Seven-day-old Sprague-Dawley rats (n = 19) underwent unilateral ligation of the left common carotid artery followed by hypoxia for 50 minutes to create mild HI injury. DTI was performed longitudinally at 5 time points from day 1 to day 90 postinjury (n = 19, 16, 13, 11, 9, respectively), and fractional anisotropy (FA), trace, radial diffusivity (λ ⊥), and axial diffusivity (λ ∥) of the injury and control contralateral ECs were quantified. Rats were randomly sacrificed (n = 15, in total), and the corresponding ECs were stained with hematoxylin-eosin, Luxol fast blue (LFB), and neurofilament (NF) to evaluate morphologic changes, amount of myelin, and axonal count at every time point. A paired t test was applied to evaluate statistical differences between both ECs, and the Pearson correlation test was used to evaluate the relationships between DTI indices and histologic evaluations. In addition, longitudinal changes in DTI indices and histologic evaluations were analyzed by a linear mixed model and an analysis of variance test, respectively. RESULTS: We demonstrated significantly decreased FA, increased λ ⊥, and similar λ ∥ in the injury compared with the control EC, which was persistent through all time points. Histologic evaluation by LFB and NF staining showed reduced myelin stain intensity in the injury EC and similar axonal counts in both ECs. Longitudinally, there was an increase in FA, a decrease in λ ⊥ and trace, and stability in λ ∥ in both ECs. Also, there was progressive reduction in the differences in FA, trace, and λ ⊥ between the injury and control EC, especially between day 1 and day 7 postinjury and in tandem with changes in myelin stain. FA was significantly correlated with myelin stain (r = 0.681, P < .01) and axonal count (r = 0.673, P < .01), whereas λ ⊥ was significantly correlated with myelin stain only (r = -0.528, P < .01), and λ ∥, with axonal count only (r = 0.372, P = .043). CONCLUSIONS: Diffusion indices can reflect dysmyelination in mild HI injury, continual myelination of both injury and control ECs with growth, and the partial recovery of myelin postinjury. We propose that diffusion indices may be used as biomarkers to monitor noninvasively the longitudinal changes of mild HI-induced WM damage.
Persistent Identifierhttp://hdl.handle.net/10722/129227
ISSN
2015 Impact Factor: 3.124
2015 SCImago Journal Rankings: 1.602
ISI Accession Number ID
Funding AgencyGrant Number
The University of Hong Kong Committee on Research and ConferenceHKU7587/06M
HKU 7793/08M
Funding Information:

This work was supported by The University of Hong Kong Committee on Research and Conference grants (HKU7587/06M and HKU 7793/08M).

References

 

DC FieldValueLanguage
dc.contributor.authorWang, Sen_HK
dc.contributor.authorWu, EXen_HK
dc.contributor.authorCai, Ken_HK
dc.contributor.authorLau, HFen_HK
dc.contributor.authorCheung, PTen_HK
dc.contributor.authorKhong, PLen_HK
dc.date.accessioned2010-12-23T08:33:45Z-
dc.date.available2010-12-23T08:33:45Z-
dc.date.issued2009en_HK
dc.identifier.citationAmerican Journal Of Neuroradiology, 2009, v. 30 n. 10, p. 1907-1913en_HK
dc.identifier.issn0195-6108en_HK
dc.identifier.urihttp://hdl.handle.net/10722/129227-
dc.description.abstractBACKGROUND AND PURPOSE: Selective white matter (WM) damage is a known sequela of mild hypoxic-ischemic (HI) injury in the neonatal rat model. The aim of this study was to evaluate longitudinally mild HI-induced WM damage (represented by the external capsule [EC]) by diffusion tensor MR imaging (DTI) and to correlate the findings with histology. MATERIALS AND METHODS: Seven-day-old Sprague-Dawley rats (n = 19) underwent unilateral ligation of the left common carotid artery followed by hypoxia for 50 minutes to create mild HI injury. DTI was performed longitudinally at 5 time points from day 1 to day 90 postinjury (n = 19, 16, 13, 11, 9, respectively), and fractional anisotropy (FA), trace, radial diffusivity (λ ⊥), and axial diffusivity (λ ∥) of the injury and control contralateral ECs were quantified. Rats were randomly sacrificed (n = 15, in total), and the corresponding ECs were stained with hematoxylin-eosin, Luxol fast blue (LFB), and neurofilament (NF) to evaluate morphologic changes, amount of myelin, and axonal count at every time point. A paired t test was applied to evaluate statistical differences between both ECs, and the Pearson correlation test was used to evaluate the relationships between DTI indices and histologic evaluations. In addition, longitudinal changes in DTI indices and histologic evaluations were analyzed by a linear mixed model and an analysis of variance test, respectively. RESULTS: We demonstrated significantly decreased FA, increased λ ⊥, and similar λ ∥ in the injury compared with the control EC, which was persistent through all time points. Histologic evaluation by LFB and NF staining showed reduced myelin stain intensity in the injury EC and similar axonal counts in both ECs. Longitudinally, there was an increase in FA, a decrease in λ ⊥ and trace, and stability in λ ∥ in both ECs. Also, there was progressive reduction in the differences in FA, trace, and λ ⊥ between the injury and control EC, especially between day 1 and day 7 postinjury and in tandem with changes in myelin stain. FA was significantly correlated with myelin stain (r = 0.681, P < .01) and axonal count (r = 0.673, P < .01), whereas λ ⊥ was significantly correlated with myelin stain only (r = -0.528, P < .01), and λ ∥, with axonal count only (r = 0.372, P = .043). CONCLUSIONS: Diffusion indices can reflect dysmyelination in mild HI injury, continual myelination of both injury and control ECs with growth, and the partial recovery of myelin postinjury. We propose that diffusion indices may be used as biomarkers to monitor noninvasively the longitudinal changes of mild HI-induced WM damage.en_HK
dc.languageengen_US
dc.publisherAmerican Society of Neuroradiology. The Journal's web site is located at http://www.ajnr.orgen_HK
dc.relation.ispartofAmerican Journal of Neuroradiologyen_HK
dc.subject.meshAnimals, Newborn-
dc.subject.meshBiological Markers-
dc.subject.meshDiffusion Magnetic Resonance Imaging-
dc.subject.meshHypoxia-Ischemia, Brain - pathology-
dc.subject.meshNerve Fibers, Myelinated - pathology-
dc.titleMild hypoxic-ischemic injury in the neonatal rat brain: Longitudinal evaluation of white matter using diffusion tensor MR imagingen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0195-6108&volume=30&issue=10&spage=1907&epage=1913&date=2009&atitle=Mild+hypoxic-ischemic+injury+in+the+neonatal+rat+brain:+Longitudinal+evaluation+of+white+matter+using+diffusion+tensor+MR+imaging-
dc.identifier.emailWu, EX:ewu1@hkucc.hku.hken_HK
dc.identifier.emailCheung, PT:ptcheung@hkucc.hku.hken_HK
dc.identifier.emailKhong, PL:plkhong@hkucc.hku.hken_HK
dc.identifier.authorityWu, EX=rp00193en_HK
dc.identifier.authorityCheung, PT=rp00351en_HK
dc.identifier.authorityKhong, PL=rp00467en_HK
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.3174/ajnr.A1697en_HK
dc.identifier.pmid19749219-
dc.identifier.scopuseid_2-s2.0-71449106807en_HK
dc.identifier.hkuros177135en_US
dc.identifier.hkuros162130-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-71449106807&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume30en_HK
dc.identifier.issue10en_HK
dc.identifier.spage1907en_HK
dc.identifier.epage1913en_HK
dc.identifier.isiWOS:000272361600019-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridWang, S=24598284300en_HK
dc.identifier.scopusauthoridWu, EX=7202128034en_HK
dc.identifier.scopusauthoridCai, K=26321372500en_HK
dc.identifier.scopusauthoridLau, HF=23004851000en_HK
dc.identifier.scopusauthoridCheung, PT=7202595465en_HK
dc.identifier.scopusauthoridKhong, PL=7006693233en_HK

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