Temporal and anatomical variations of brain water apparent diffusion coefficient in perinatal cerebral hypoxic‐ischemic injury: Relationships to cerebral energy metabolism

Thornton, John S.; Ordidge, Roger J.; Penrice, J; Cady, Ernest B.; Amess, P; Punwani, Shonit; Clemence, M; Wyatt, JS

doi:10.1002/mrm.1910390609

Cited by 71 publications

(47 citation statements)

References 26 publications

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“…One of the most striking aspects of hypoxia-ischemia is the progressive evolution of damage into previously uninjured areas over days to weeks after the insult (56). The mechanisms of this spread are not understood, but gap junctions between glia have been suggested to play an important role through a "gap junction-mediated bystander effect" (57).…”

Section: Mechanisms Of Spread Of Inflammation-induced Injury Through mentioning

confidence: 99%

Astrocytes and microglia in acute cerebral injury underlying cerebral palsy associated with preterm birth

et al. 2013

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Section: Mechanisms Of Spread Of Inflammation-induced Injury Through mentioning

confidence: 99%

Astrocytes and microglia in acute cerebral injury underlying cerebral palsy associated with preterm birth

et al. 2013

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“…In the RVM, changes in diffusion have been associated with secondary loss of highenergy phosphates (11) and the magnitude of this impairment correlates with injury severity (12). Since the duration of the cerebrovascular insult was similar in both models (i.e., 1.5 h), the major differentiating features were the presence (RVM) or absence (tfMCAO) of an hypoxic insult, the obstruction of a larger (RVM) or smaller (tfMCAO) caliber artery, and the fact that in the RVM an inflow artery with a distal Circle of Willis is used whereas in the tfMCAO an end artery is occluded.…”

Section: Ischemic Injury In the Rat Pupmentioning

confidence: 99%

Comparison of Two Neonatal Ischemic Injury Models Using Magnetic Resonance Imaging

Ashwal¹,

Tone²,

Tian³

et al. 2007

Pediatr Res

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Using an 11.7-Tesla magnetic resonance imaging (MRI) scanner in 10-d-old rat pups we report on the evolution of injury over 28 d in a model of neonatal stroke (transient filament middle cerebral artery occlusion, tfMCAO) and a model of hypoxicischemic injury (Rice-Vannucci model, RVM). In both models, diffusion-weighted imaging (DWI) was more sensitive in the early detection of ischemia than T2-weighted imaging (T2WI). Injury volumes in both models were greater on d 1 for DWI and d 3 for T2WI, decreased over time and by d 28 T2WI injury volumes (tfMCAO 10.3% of ipsilateral hemisphere; RVM 23.9%) were definable. The distribution of injury with tfMCAO was confined to the vascular territory of the middle cerebral artery and a definable core and penumbra evolved over time. Ischemic injury in the RVM was more generalized and greater in cortical regions. Contralateral hemispheric involvement was only observed in the RVM. Our findings demonstrate that high-field MRI over extended periods of time is possible in a small animal model of neonatal brain injury and that the tfMCAO model should be used for studies of neonatal stroke and that the RVM does not reflect the vascular distribution of injury seen with focal ischemia. (Pediatr Res 61: 9-14, 2007) C urrent neuroprotective therapies of acute stroke in adults have not proven beneficial and because the delay in diagnosis of neonatal stroke is beyond the current window of opportunity for thrombolytic therapy, it is likely that future neonatal care will focus on delayed treatments implemented hours to days after ischemia. Temporally delayed treatment is even more likely in cases of neonatal ischemia as observable signs are more difficult to assess and observe. As such, being able to serially and noninvasively monitor the evolution of neonatal stroke in humans as well as animal models over weeks to months would be advantageous in studying mechanisms of injury, repair and responses to treatment. Magnetic resonance imaging (MRI) has greatly improved our ability to detect stroke in newborns but its use in neonatal stroke models has been limited by the technical challenges in serially acquiring such data (1,2).The current study used high field strength (11.7T; Tesla) MRI to study the evolution of neonatal hypoxic-ischemic injury over a period of 28 d in two different models. We chose to compare a model of neonatal stroke (tfMCAO, transient filament middle cerebral artery occlusion) to that of the more commonly used model of neonatal hypoxic-ischemic brain injury (RVM, Rice-Vannucci model of unilateral carotid ligation and 1.5 h of hypoxia). We hypothesized that MRI could be used in a small animal model to serially and noninvasively monitor the evolution of injury over 28 d and that neuroimaging could elucidate temporal and spatial patterns of injury in the two models. Specifically, we wished to determine whether there were neuroimaging differences between the two models in: (1) the distribution of injury; (2) the degree of injury in striatum and cortex; (3) the evolut...

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“…12,19 -21 The reversal of these acute DWI abnormalities was only transient, and ischemic lesions became detectable again at later time points by MRI and histology. [22][23][24][25][26][27] We recently showed that even if DWI lesions reversed in the early reperfusion period after 30 minutes of ischemia, they recurred by 1 day. 28 However, detailed histological analysis of this reversed tissue has not been performed, and whether there is underlying pathology in the reversed tissue is not known.…”

mentioning

confidence: 99%

Reversal of Early Diffusion-Weighted Magnetic Resonance Imaging Abnormalities Does Not Necessarily Reflect Tissue Salvage in Experimental Cerebral Ischemia

Ringer

Neumann‐Haefelin

Sobel

et al. 2001

Stroke

105

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Background and Purpose-Diffusion-weighted MRI (DWI) can detect early ischemic changes and is sometimes used as a surrogate neurological end point in clinical trials. Recent experimental stroke studies have shown that with brief periods of ischemia, some DWI lesions transiently reverse, only to recur later. This study examined the histological condition of the tissue during the period of DWI reversal. Methods-Rats underwent 30 minutes of middle cerebral artery occlusion followed by reperfusion. DWI images were obtained during ischemia and 3 to 5 hours, 1 day, and 7 days later. MRI scans were compared with histology (5 hours, nϭ5; 7 days, nϭ5) with the use of neuronal (microtubule-associated protein 2 [MAP2]) and astrocytic (glial fibrillary acidic protein [GFAP]) markers and heat-shock protein 72 (HSP72). Results-DWI abnormalities reversed 3 to 5 hours after ischemia onset but recurred at 1 day. Four animals showed complete reversal of the initial DWI hyperintensity, and 6 showed partial reversal. When the 5-hour DWI was completely normal, there was significant loss of MAP2 immunoreactivity, comprising approximately 30% of the initial DWI lesion. However, GFAP staining revealed morphologically normal astrocytes. HSP72 immunoreactivity at 5 hours was extensive and corresponded to the initial DWI lesion. Conclusions-After brief ischemic periods, normalization of the DWI does not necessarily imply that the tissue is normal.Neurons already exhibit evidence of structural damage and stress. Normal GFAP staining suggests that other nonneuronal cell populations may partially compensate for altered fluid balances at the time of DWI reversal despite the presence of neuronal injury. These observations suggest that caution is warranted when relying solely on DWI for assessment of ischemic damage.

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Temporal and anatomical variations of brain water apparent diffusion coefficient in perinatal cerebral hypoxic‐ischemic injury: Relationships to cerebral energy metabolism

Cited by 71 publications

References 26 publications

Astrocytes and microglia in acute cerebral injury underlying cerebral palsy associated with preterm birth

Astrocytes and microglia in acute cerebral injury underlying cerebral palsy associated with preterm birth

Comparison of Two Neonatal Ischemic Injury Models Using Magnetic Resonance Imaging

Reversal of Early Diffusion-Weighted Magnetic Resonance Imaging Abnormalities Does Not Necessarily Reflect Tissue Salvage in Experimental Cerebral Ischemia

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