Diffusion Tensor Imaging Abnormalities in the Cerebral White Matter Correlate with Sex-Dependent Neurobehavioral Deficits in Adult Mice with Neonatal Ischemia

2016 ◽  
Vol 38 (2) ◽  
pp. 83-95 ◽  
Author(s):  
Markus Breu ◽  
Jiangyang Zhang ◽  
Michael Porambo ◽  
Mikhail V. Pletnikov ◽  
Katharina Goeral ◽  
...  
Keyword(s):  
Cerebral Palsy ◽  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Diffusion Tensor ◽  
Behavioral Testing ◽  
Behavioral Alterations ◽  
Neonatal Ischemia ◽  
And Control

Background: Neonatal white matter injury (NWMI) is the leading cause of cerebral palsy in prematurely born children. In order to develop a test bed for therapeutics, we recently reported a mouse model of NWMI by using a modified Rice-Vannucci model of neonatal ischemia on postnatal day 5 (P5) in CD-1 mice. We have previously shown that these mice illustrate initial neuroinflammation and oligodendroglial differentiation arrest followed by long-term dysmyelination, periventricular astrogliosis and axonal injury, resembling human NWMI. The objective of this study was to determine the sex-dependent long-term effects of neonatal brain injury on neurobehavioral and advanced in vivo neuroimaging indices in this mouse model, and to correlate these variables with histopathology. Methods: After right common artery ligation on P5, in vivo T2-weighted imaging and diffusion tensor imaging (DTI) were performed on ligated and control animals at 4 and 8 weeks. Common sets of regions of interest were used to compare fractional anisotropy (FA) values between ischemic and control mice. Behavioral testing (open field, startle response and grip strength) was performed at adult age. Finally, the animals were sacrificed for immunohistochemical (IHC) assessment of major white matter tracts. Results: DTI revealed significant sex-dependent changes in FA values ipsi- and contralateral to the ligation. Behavioral testing showed decreased reaction to acoustic stimuli in males but not females. Similarly, increased number of rearings and lack of novelty-induced habituation in the open field were encountered only in the male subgroup. Several regional correlations were found between FA values and these behavioral alterations. IHC studies revealed degeneration of mature oligodendrocytes and damage of white matter tracts in ligated animals, as previously reported in this model, and showed regional correlation with in vivo FA values and behavioral alterations. Conclusions: Our findings suggest structural sex-dependent long-term abnormalities after neonatal ischemia. These changes lead to behavioral deficits resembling common problems of patients with cerebral palsy.

scholarly journals Long-term clinically relevant rodent model of methotrexate-induced cognitive impairment

2020 ◽  
Vol 22 (8) ◽  
pp. 1126-1137 ◽  
Author(s):  
Connor Berlin ◽  
Katharine Lange ◽  
H Carl Lekaye ◽  
Kelsey Hopland ◽  
Samantha Phillips ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Diffusion Tensor ◽  
Negative Impact ◽  
Survival Rates ◽  
High Dose ◽  
Significant Negative Impact

Abstract Background With the enhanced use of chemotherapy and the advent of increased patient survival rates, there are an increasing number of cancer survivors living with chemotherapy-induced cognitive impairment. A growing number of clinical studies have brought to light the association of agents like methotrexate in generating these neurological sequelae, although mechanisms remain unclear. Methods Here, we use a clinically relevant regimen of several cycles of methotrexate and leucovorin rescue to develop a model of chemotherapy-induced cognitive impairment, and investigate the in vivo long-term (16 mo) impact of high-dose systemic methotrexate on white matter cellular dynamics as assessed by stereology, animal behavior, and diffusion tensor imaging. Results Our results indicate that at 6 and 16 months post-chemotherapy, methotrexate-treated rats exhibit a significant and permanent decrease in the number of oligodendrocytes and their progenitors in the white matter, in corpus callosum volumes, and myelin basic protein. These findings are associated with mostly delayed deficits in performance on Morris Water Maze and Novel Object Recognition tasks. Diffusion tensor imaging demonstrates significantly decreased fractional anisotropy values in the callosum genu, body, and splenium, as well as previously unassessed areas like the fimbria. Interestingly, these white matter changes are preceded by an earlier, transient decrement in white matter microglia at 3 months, and hippocampal neural progenitors at 3 and 6 months. Conclusion These results demonstrate a significant negative impact of methotrexate on the oligodendrocyte compartment and white matter, associated with cognitive impairment. The data also support the use of diffusion tensor imaging in monitoring white matter integrity in this context.

White matter microstructure predicts longitudinal social cognitive outcomes after paediatric traumatic brain injury: a diffusion tensor imaging study

2017 ◽  
Vol 48 (4) ◽  
pp. 679-691 ◽  
Author(s):  
N. P. Ryan ◽  
S. Genc ◽  
M. H. Beauchamp ◽  
K. O. Yeates ◽  
S. Hearps ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Social Cognitive ◽  
Diffusion Tensor ◽  
Cognitive Outcomes ◽  
Pragmatic Language ◽  
Post Injury ◽  
White Matter Microstructure

BackgroundDeficits in social cognition may be among the most profound and disabling sequelae of paediatric traumatic brain injury (TBI); however, the neuroanatomical correlates of longitudinal outcomes in this domain remain unexplored. This study aimed to characterize social cognitive outcomes longitudinally after paediatric TBI, and to evaluate the use of sub-acute diffusion tensor imaging (DTI) to predict these outcomes.MethodsThe sample included 52 children with mild complex-severe TBI who were assessed on cognitive theory of mind (ToM), pragmatic language and affective ToM at 6- and 24-months post-injury. For comparison, 43 typically developing controls (TDCs) of similar age and sex were recruited. DTI data were acquired sub-acutely (mean = 5.5 weeks post-injury) in a subset of 65 children (TBI = 35; TDC = 30) to evaluate longitudinal prospective relationships between white matter microstructure assessed using Tract-Based Spatial Statistics and social cognitive outcomes.ResultsWhole brain voxel-wise analysis revealed significantly higher mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) in the sub-acute TBI group compared with TDC, with differences observed predominantly in the splenium of the corpus callosum (sCC), sagittal stratum (SS), dorsal cingulum (DC), uncinate fasciculus (UF) and middle and superior cerebellar peduncles (MCP & SCP, respectively). Relative to TDCs, children with TBI showed poorer cognitive ToM, affective ToM and pragmatic language at 6-months post-insult, and those deficits were related to abnormal diffusivity of the sCC, SS, DC, UF, MCP and SCP. Moreover, children with TBI showed poorer affective ToM and pragmatic language at 24-months post-injury, and those outcomes were predicted by sub-acute alterations in diffusivity of the DC and MCP.ConclusionsAbnormal microstructure within frontal-temporal, limbic and cerebro-cerebellar white matter may be a risk factor for long-term social difficulties observed in children with TBI. DTI may have potential to unlock early prognostic markers of long-term social outcomes.

scholarly journals Diffusion Tensor Imaging Changes Do Not Affect Long-Term Neurodevelopment Following Early Erythropoietin Among Extremely Preterm Infants in the Preterm Erythropoietin Neuroprotection Trial

2021 ◽  
Vol 11 (10) ◽  
pp. 1360
Author(s):  
Janessa B. Law ◽  
Bryan A. Comstock ◽  
Todd L. Richards ◽  
Christopher M. Traudt ◽  
Thomas R. Wood ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Linear Models ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Neurodevelopmental Outcomes ◽  
Extremely Preterm ◽  
Extremely Preterm Infants ◽  
Postmenstrual Age

We aimed to evaluate diffusion tensor imaging (DTI) in infants born extremely preterm, to determine the effect of erythropoietin (Epo) on DTI, and to correlate DTI with neurodevelopmental outcomes at 2 years of age for infants in the Preterm Erythropoietin Neuroprotection (PENUT) Trial. Infants who underwent MRI with DTI at 36 weeks postmenstrual age were included. Neurodevelopmental outcomes were evaluated by Bayley Scales of Infant and Toddler Development (BSID-III). Generalized linear models were used to assess the association between DTI parameters and treatment group, and then with neurodevelopmental outcomes. A total of 101 placebo- and 93 Epo-treated infants underwent MRI. DTI white matter mean diffusivity (MD) was lower in placebo- compared to Epo-treated infants in the cingulate and occipital regions, and occipital white matter fractional isotropy (FA) was lower in infants born at 24–25 weeks vs. 26–27 weeks. These values were not associated with lower BSID-III scores. Certain decreases in clustering coefficients tended to have lower BSID-III scores. Consistent with the PENUT Trial findings, there was no effect on long-term neurodevelopment in Epo-treated infants even in the presence of microstructural changes identified by DTI.

scholarly journals In vivo diffusion tensor imaging and ex vivo histologic characterization of white matter pathology in a post-status epilepticus model of temporal lobe epilepsy

Epilepsia ◽  
2011 ◽  
Vol 52 (4) ◽  
pp. 841-845 ◽  
Author(s):  
Pieter van Eijsden ◽  
Wim M. Otte ◽  
W. Saskia van der Hel ◽  
Onno van Nieuwenhuizen ◽  
Rick M. Dijkhuizen ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
Status Epilepticus ◽  
White Matter ◽  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Diffusion Tensor ◽  
Ex Vivo ◽  
White Matter Pathology

End-Stage Renal Disease: In Vivo Diffusion-Tensor Imaging of Silent White Matter Damage

Radiology ◽  
2009 ◽  
Vol 252 (2) ◽  
pp. 518-525 ◽  
Author(s):  
Tsyh-Jyi Hsieh ◽  
Jer-Ming Chang ◽  
Hung-Yi Chuang ◽  
Chih-Hung Ko ◽  
Miao-Ling Hsieh ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Diffusion Tensor ◽  
White Matter Damage ◽  
Stage Renal Disease ◽  
End Stage
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