<i>Ex Vivo</i> Diffusion Tensor Imaging and Neuropathological Correlation in a Murine Model of Hypoxia–Ischemia-Induced Thrombotic Stroke

Shereen, A. Duke; Nemkul, Niza; Yang, Dianer; Adhami, Faisal; Dunn, Richard S.; Hazen, Missy L.; Nakafuku, Masato; Ning, Gang; Lindquist, Diana M.; Kuan, Chia Yi

doi:10.1038/jcbfm.2010.212

Cited by 62 publications

(62 citation statements)

References 38 publications

(74 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…7 Other pathological changes in ischemic WM include segmental swelling of myelinated axons and the formation of spaces or vacuoles between the myelin sheath and axolemma ( Figure 1). 7,8 These observations confirm that WM is vulnerable to ischemia and that this insult damages oligodendrocytes, myelin, and axons in a manner that can proceed independently from neuronal perikaryal injury. In fact, up to 25% of ischemic strokes in humans are of the lacunar variety and are confined to WM areas such as the internal capsule.…”

supporting

confidence: 67%

“…When exposed to hypoxia or ischemia, these cells exhibit robust production of superoxide radical, lipid peroxidation, and conversion of iron stores to the oxidizing agent, ferrous ion. 8 The antioxidant ebselen significantly reduces axonal and oligodendrocyte damage as well as the neurological deficit associated with transient ischemia when administered 2 hours after the onset of stroke. 27 More antioxidants should be tested in models of pure WM ischemia to gain deeper insight into the therapeutic potential of this class of compounds.…”

Section: +mentioning

confidence: 99%

See 1 more Smart Citation

Protecting White Matter From Stroke Injury

Matute

Domercq

Pérez-Samartı́n

et al. 2013

Stroke

View full text Add to dashboard Cite

W hite matter (WM) exclusively contains axons and their glial cell partners including astrocytes, oligodendrocytes (myelinating and nonmyelinating), and microglia. WM comprises about half of the forebrain volume of humans, a 3-to 4-fold increase over rodents, the animals most used for neuroscience research.1,2 The low relative volume of WM in rodents led to neglect of this specialized brain area in studies of stroke pathophysiology and under-appreciation of the clinical importance of WM that has slowed progress to effective therapy.3 WM axons interconnect distant regions of the central nervous system and are metabolically independent of their cell bodies with regard to energy metabolism. Hence, proper propagation of electrical signals through WM axons demands a continuous supply of energy along their entire length and focal disruption of blood supply may compromise the viability of the whole axon. Yet, WM receives disproportionally less circulation than gray matter (GM) and is highly vulnerable to reduced blood supply exemplified by the frequency of pure WM strokes called lacunes or lacunar infarcts, 4 which can accumulate, sometimes silently, and produce vascular dementia. 5Damage of WM is a major cause of functional disability in cerebrovascular disease and the majority of ischemic strokes involve both WM and GM. 2,6 Early animal studies indicate that WM can be damaged by even brief focal ischemia.7 Thus, after 30 minutes of arterial occlusion massive swelling of oligodendrocytes and astrocytes occurs, and about 3 hours later most oligodendrocytes die. These changes precede by several hours the appearance of necrotic neurons in ischemic regions. 7 Other pathological changes in ischemic WM include segmental swelling of myelinated axons and the formation of spaces or vacuoles between the myelin sheath and axolemma (Figure 1). 7,8 These observations confirm that WM is vulnerable to ischemia and that this insult damages oligodendrocytes, myelin, and axons in a manner that can proceed independently from neuronal perikaryal injury. In fact, up to 25% of ischemic strokes in humans are of the lacunar variety and are confined to WM areas such as the internal capsule. The clinical importance of WM ischemic injury increases because the most susceptible population, the elderly, constitutes a larger and larger fraction of world population. Some types of dementia may actually represent a chronic and stealthy form of ischemia exclusive to WM. Stroke, therefore, produces disability not only as a result of dysfunction of neurons and synapses, but also by primary or secondary damage to WM axons and glia. This review summarizes current knowledge of the molecular mechanisms of ischemic injury to WM and discusses its translational implications for the treatment of stroke (Table). [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] White Matter MetabolismGlucose is the primary energy source in the adult brain. Glucose transporter (GLUT) proteins on endothelial cells, glial cells, and axons are n...

show abstract

supporting

confidence: 67%

Section: +mentioning

confidence: 99%

Protecting White Matter From Stroke Injury

Matute

Domercq

Pérez-Samartı́n

et al. 2013

Stroke

View full text Add to dashboard Cite

show abstract

“…Table 4 describes the results of DTI and MTI in various settings and disease entities. Animal models and postmortem studies indicate that increased fractional anisotropy and mean diffusivity derived from DTI and magnetization transfer ratio from MTI correlate with axonal loss, demyelination and dentritic injury [29,36,70,76]. A recent study in hypoperfused mice is of particular interest as it examined the complementary value of DTI and MTI measures for delineation of white matter damage [36].…”

Section: Age-related White Matter Changes and Normal-appearing Brain mentioning

confidence: 99%

Heterogeneity in age-related white matter changes

et al. 2011

View full text Add to dashboard Cite

White matter changes occur endemically in routine magnetic resonance imaging (MRI) scans of elderly persons. MRI appearance and histopathological correlates of white matter changes are heterogeneous. Smooth periventricular hyperintensities, including caps around the ventricular horns, periventricular lining and halos are likely to be of non-vascular origin. They relate to a disruption of the ependymal lining with subependymal widening of the extracellular space and have to be differentiated from subcortical and deep white matter abnormalities. For the latter a distinction needs to be made between punctate, early confluent and confluent types. Although punctate white matter lesions often represent widened perivascular spaces without substantial ischemic tissue damage, early confluent and confluent lesions correspond to incomplete ischemic destruction. Punctate abnormalities on MRI show a low tendency for progression, while early confluent and confluent changes progress rapidly. The causative and modifying pathways involved in the occurrence of sporadic age-related white matter changes are still incompletely understood, but recent microarray and genome-wide association approaches increased the notion of pathways that might be considered as targets for therapeutic intervention. The majority of differentially regulated transcripts in white matter lesions encode genes associated with immune function, cell cycle, proteolysis, and ion transport. Genome-wide association studies identified six SNPs mapping to a locus on chromosome 17q25 to be related to white matter lesion load in the general population. We also report first and preliminary data that demonstrate apolipoprotein E (ApoE) immunoreactivity in white matter lesions and support epidemiological findings indicating that ApoE is another factor possibly related to white matter lesion occurrence. Further insights come from modern MRI techniques, such as diffusion tensor and magnetization transfer imaging, as they provide tools for the characterization of

show abstract

“…Animal models and postmortem studies indicate that quantitative DTI and MTI measures correlate with markers of myelin integrity, and axonal damage and density. [65][66][67][68] A study in brain hypoperfused mice examined the complementary value of DTI and MTI measures for delineation of white matter damage. 68 After continuous moderate hypoperfusion over 1 month the authors found that the reduction in fractional anisotropy paralleled a decrease in magnetization transfer ratio in several tissue compartments.…”

Section: Microstructural Changes In Normal-appearing Brain Tissuementioning

confidence: 99%

Longitudinal change of small-vessel disease-related brain abnormalities

Schmidt

Seiler

Loitfelder

2015

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Knowledge about the longitudinal change of cerebral small-vessel disease-related magnetic resonance imaging abnormalities increases our pathophysiologic understanding of cerebral microangiopathy. The change of specific lesion types may also serve as secondary surrogate endpoint in clinical trials. A surrogate endpoint needs to progress fast enough to allow monitoring of treatment effects within a reasonable time period, and change of the brain abnormality needs to be correlated with clinical change. Confluent white matter lesions show fast progression and correlations with cognitive decline. Thus, the change of confluent white matter lesions may be used as a surrogate marker in proof-of-concept trials with small patient numbers needed to show treatment effects on lesion progression. Nonetheless if the expected change in cognitive performance resulting from treatment effects on lesion progression is used as outcome, the sample size needed to show small to moderate treatment effects becomes very large. Lacunes may also fulfill the prerequisites of a surrogate marker, but in the general population the incidence of lacunes over short observational periods is small. For other small-vessel disease-related brain abnormalities including microbleeds and microstructural changes in normalappearing white matter longitudinal change and correlations with clinical decline is not yet fully determined.

show abstract

Ex Vivo Diffusion Tensor Imaging and Neuropathological Correlation in a Murine Model of Hypoxia–Ischemia-Induced Thrombotic Stroke

Cited by 62 publications

References 38 publications

Protecting White Matter From Stroke Injury

Protecting White Matter From Stroke Injury

Heterogeneity in age-related white matter changes

Longitudinal change of small-vessel disease-related brain abnormalities

Contact Info

Product

Resources

About