Serial magnetic resonance imaging in a rat pup filament stroke model

Ashwal, Stephen; Tone, Beatriz; Tian, Hui; Chong, S.; Obenaus, André

doi:10.1016/j.expneurol.2006.06.004

Cited by 24 publications

(34 citation statements)

References 33 publications

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“…All MR data sets were quantified using standard previously published protocols (13). Briefly T2 relaxation rates were determined by varying the echo time (TE) from 10 to 100 ms. Coefficients were determined from exponential fits for each pixel of the T2 data series to generate T2 maps.…”

Section: Methodsmentioning

confidence: 99%

Temporal and Regional Evolution of Aquaporin-4 Expression and Magnetic Resonance Imaging in a Rat Pup Model of Neonatal Stroke

et al. 2007

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Edema formation can be observed using magnetic resonance imaging (MRI) in patients with stroke. Recent studies have shown that aquaporin-4 (AQP4), a water channel, is induced early after stroke and potentially participates in the development of brain edema. We studied whether induction of AQP4 correlated with edema formation in a rat pup filament stroke model using high field (11.7-Tesla) MRI followed by immunohistochemical investigation of AQP4 protein expression. At 24 h, we observed increased T2 values and decreased apparent diffusion coefficients (ADC) within injured cortical and striatal regions that reflected the edema formation. Coincident with these MR changes were significant increases in AQP4 expression on astrocytic end-feet in the border regions of injured tissues. Striatal imaging findings were still present at 72 h with a slow normalization of AQP4 expression in the border regions. At 28 d, AQP4 expression normalized in the border while in this region ADC values increased. We show that induction of AQP4 is increased during the period of active edema formation in the border region without regional correlation with edema. Finally, induction of AQP4 on astrocyte end-feet could participate in tissue preservation after ischemia in the immature rat brain. A rterial ischemic stroke, often within the distribution of the MCA, occurs in approximately 1 per 4,000 neonates and as in adults there are significant sequelae over the lifespan that make this disease an important public health concern (1). Increasingly, magnetic resonance imaging (MRI) is used to evaluate neonatal ischemic brain injury and several recent studies have demonstrated the added value of DWI in assessing injury severity and in determining long-term outcome (2-4). MRI also has been used to visualize brain edema that contributes to the morbidity and mortality of many of these conditions (5). In general, diffusion restriction with reduced ADC values correlates with cytotoxic edema, whereas increased T2WI values reflects the development of vasogenic edema (6,7).In the past decade, attention has focused on AQP in the development of brain edema. AQP are water-specific channels that provide a direct water route through the plasma membrane and are important in the regulation of water movement. Expression of AQP4 and AQP9, detected in mammalian brain, is altered in several conditions, including ischemia (7-9). Although astrocytic expression of AQP4 and AQP9 increases after ischemia, only AQP4 expression temporally correlates with the evolution of brain edema in adult mice and suggests that regulation of AQP4 expression could be a potential therapeutic target (9).The role of AQP4 in the evolution of cytotoxic and vasogenic edema after stroke remains uncertain. In the adult mouse, increased astrocytic AQP4 expression was observed at 1 h and 48 h after stroke (9). In contrast to adult stroke model studies, investigations in a neonatal rat pup model of HII found that AQP4 expression (decreased at 1 h and 24 h after HII), was associated with d...

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Section: Methodsmentioning

confidence: 99%

Temporal and Regional Evolution of Aquaporin-4 Expression and Magnetic Resonance Imaging in a Rat Pup Model of Neonatal Stroke

et al. 2007

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“…Models of permanent MCA ligation 11 and transient MCAO (tMCAO) induced in P7 to P10 rats 10,12,73 accomplished by a transient insertion of a suture filament enabled studies of perinatal arterial stroke. Varying the length of tMCAO has allowed production of injuries of different severity.…”

Section: Animal Models and The Underlying Mechanisms Of Perinatal Artmentioning

confidence: 99%

“…13,74,78,79 Figure 1B shows that diffusion-weighted MRI depicts expansion of tissue 'at risk' associated with longer MCAO duration. Other MRI modalities have been proven useful in determining the extent of microcirculatory disturbances during MCAO and after reperfusion (perfusion-sensitive MRI), 76 disruption of the blood-brain barrier (BBB) (Gd-enhanced T1W imaging), 76 elucidation of the evolving injury (T2W imaging), 56,73,80 and changes in brain connectivity after injury during the neonatal period (diffusion tensor imaging). 81 Studies in tMCAO and H-I models in neonatal rodents have shown that although the components of injury that induce cell death and brain injury are similar to those occurring in experimental models of preterm injury-excitotoxic, oxidant, and inflammatory components-the targeted cell populations and regions affected by cerebral hypoxia and ischemia are different.…”

Section: Animal Models and The Underlying Mechanisms Of Perinatal Artmentioning

confidence: 99%

Mechanisms of Perinatal Arterial Ischemic Stroke

Fernández-López

Natarajan

Ashwal

et al. 2014

J Cereb Blood Flow Metab

108

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The incidence of perinatal stroke is high, similar to that in the elderly, and produces a significant morbidity and severe long-term neurologic and cognitive deficits, including cerebral palsy, epilepsy, neuropsychological impairments, and behavioral disorders. Emerging clinical data and data from experimental models of cerebral ischemia in neonatal rodents have shown that the pathophysiology of perinatal brain damage is multifactorial. These studies have revealed that, far from just being a smaller version of the adult brain, the neonatal brain is unique with a very particular and age-dependent responsiveness to hypoxia-ischemia and focal arterial stroke. In this review, we discuss fundamental clinical aspects of perinatal stroke as well as some of the most recent and relevant findings regarding the susceptibility of specific brain cell populations to injury, the dynamics and the mechanisms of neuronal cell death in injured neonates, the responses of neonatal blood-brain barrier to stroke in relation to systemic and local inflammation, and the long-term effects of stroke on angiogenesis and neurogenesis. Finally, we address translational strategies currently being considered for neonatal stroke as well as treatments that might effectively enhance repair later after injury.

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“…Visual and manual lesion assessments which are commonly used [ 1,[3][4][5][6] suffer from the misperception of contrast due to the parallax effects of neighboring pixels/ voxels-pixels with the same intensity values may look different due to its neighboring pixels [ 7,8 ] . Issues such as user fatigue related errors in time-consuming manual assessment methods and intra-and interobserver variability potentially compromise data comparisons.…”

Section: Current Computational Approaches For Lesion Detectionmentioning

confidence: 99%

“…The last 2 decades have seen a rapid progression of scientifi c and clinical advances due in large part to the implementation and application of neuroimaging, including magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET). Numerous reviews (including chapters in this book) highlight the importance of neuroimaging for diagnosis and assessment of therapeutic effectiveness [ 1,2 ] . Visual assessment is used primarily to guide clinical decisions for patient care, but what is lacking in clinical and experimental studies is the ability to rapidly extract quantitative data.…”

Section: Introductionmentioning

confidence: 99%

Computational Analysis: A Bridge to Translational Stroke Treatment

Ghosh

Sun

Turenius

et al. 2012

Translational Stroke Research

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Objective rapid quantifi cation of injury using computational methods can improve the assessment of the degree of stroke injury, aid in the selection of patients for early or specifi c treatments, and monitor the evolution of injury and recovery. In this chapter, we use neonatal ischemia as a case-study of the application of several computational methods that in fact are generic and applicable across the age and disease spectrum. We provide a summary of current computational approaches used for injury detection, including Gaussian mixture models (GMM), Markov random fi elds (MRFs), normalized graph cut, and K-means clustering. We also describe more recent automated approaches to segment the region(s) of ischemic injury including hierarchical region splitting, support vector machine, a brain symmetry/asymmetry integrated model, and a watershed method that are robust at different developmental stages. We conclude with our assessment of probable future research directions in the fi eld of computational noninvasive stroke analysis such as automated detection of the ischemic core and penumbra, monitoring of implanted neuronal stem cells in the ischemic brain, injury localization specifi c to different brain anatomical regions, and quantifi cation of stroke evolution, recovery and spatiotemporal interactions between injury volume/severity and treatment. Computational analysis is expected to open a new horizon in current clinical and translational stroke research by exploratory data mining that is not detectable using the standard "methods" of visual assessment of imaging data.

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Serial magnetic resonance imaging in a rat pup filament stroke model

Cited by 24 publications

References 33 publications

Temporal and Regional Evolution of Aquaporin-4 Expression and Magnetic Resonance Imaging in a Rat Pup Model of Neonatal Stroke

Temporal and Regional Evolution of Aquaporin-4 Expression and Magnetic Resonance Imaging in a Rat Pup Model of Neonatal Stroke

Mechanisms of Perinatal Arterial Ischemic Stroke

Computational Analysis: A Bridge to Translational Stroke Treatment

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