scholarly journals Exploring cell membrane water exchange in aquaporin-4-deficient ischemic mouse brain using diffusion-weighted MRI

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Takuya Urushihata ◽  
Hiroyuki Takuwa ◽  
Manami Takahashi ◽  
Jeff Kershaw ◽  
Yasuhiko Tachibana ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Diffusion Weighted Imaging ◽  
Water Exchange ◽  
Focal Cerebral Ischemia ◽  
Diffusion Time ◽  
Exchange Model ◽  
Aquaporin 4 ◽  
Wild Type ◽  
Diffusion Weighted ◽  
Ischemic Tissue

Abstract Background Aquaporin-4 is a membrane channel protein that is highly expressed in brain astrocytes and facilitates the transport of water molecules. It has been suggested that suppression of aquaporin-4 function may be an effective treatment for reducing cellular edema after cerebral infarction. It is therefore important to develop clinically applicable measurement systems to evaluate and better understand the effects of aquaporin-4 suppression on the living body. Methods Animal models of focal cerebral ischemia were created by surgically occluding the middle cerebral artery of wild-type and aquaporin-4 knockout mice, after which multi-b-value multi-diffusion-time diffusion-weighted imaging measurements were performed. Data were analyzed with both the apparent diffusion coefficient (ADC) model and a compartmental water-exchange model. Results ADCs were estimated for five different b value ranges. The ADC of aquaporin-4 knockout mice in the contralateral region was significantly higher than that of wild-type mice for each range. In contrast, aquaporin-4 knockout mice had significantly lower ADC than wild-type mice in ischemic tissue for each b-value range. Genotype-dependent differences in the ADC were particularly significant for the lowest ranges in normal tissue and for the highest ranges in ischemic tissue. The ADCs measured at different diffusion times were significantly different for both genotypes. Fitting of the water-exchange model to the ischemic region data found that the water-exchange time in aquaporin-4 knockout mice was approximately 2.5 times longer than that in wild-type mice. Conclusions Multi-b-value multi-diffusion-time diffusion-weighted imaging may be useful for in vivo research and clinical diagnosis of aquaporin-4-related diseases.

scholarly journals Increased cerebral vascularization and decreased water exchange across the blood-brain barrier in aquaporin-4 knockout mice

PLoS ONE ◽  
2019 ◽  
Vol 14 (6) ◽  
pp. e0218415 ◽  
Author(s):  
Yifan Zhang ◽  
Kui Xu ◽  
Yuchi Liu ◽  
Bernadette O. Erokwu ◽  
Pan Zhao ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Knockout Mice ◽  
Water Exchange ◽  
Aquaporin 4 ◽  
Brain Barrier ◽  
Blood Brain

Reversible diffusion-weighted imaging lesions in acute ischemic stroke

Neurology ◽  
2020 ◽  
Vol 94 (13) ◽  
pp. 571-587 ◽  
Author(s):  
Nandakumar Nagaraja ◽  
John R. Forder ◽  
Steven Warach ◽  
Jośe G. Merino
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Endovascular Therapy ◽  
Diffusion Weighted Imaging ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Nihss Score ◽  
Diffusion Weighted ◽  
Ischemic Tissue ◽  
Fluid Attenuated Inversion Recovery

ObjectivesTo systematically review the literature for reversible diffusion-weighted imaging (DWIR) lesions and to describe its prevalence, predictors, and clinical significance.MethodsStudies were included if the first DWI MRI was performed within 24 hours of stroke onset and follow-up DWI or fluid-attenuated inversion recovery (FLAIR)/T2 was performed within 7 or 90 days, respectively, to measure DWIR. We abstracted clinical, imaging, and outcomes data.ResultsTwenty-three studies met the study criteria. The prevalence of DWIR was 26.5% in DWI-based studies and 6% in FLAIR/T2-based studies. DWIR was associated with recanalization or reperfusion of the ischemic tissue with or without the use of tissue plasminogen activator (t-PA) or endovascular therapy, earlier treatment with t-PA, shorter time to endovascular therapy after MRI, and absent or less severe perfusion deficit within the DWI lesion. DWIR was associated with early neurologic improvement in 5 of 6 studies (defined as improvement in the NIH Stroke Scale (NIHSS) score by 4 or 8 points from baseline or NIHSS score 0 to 2 at 24 hours after treatment or at discharge or median NIHSS score at 7 days) and long-term outcome in 6 of 7 studies (defined as NIHSS score ≤1, improvement in the NIHSS score ≥8 points, or modified Rankin Scale score up to ≤2 at 30 or 90 days) likely due to reperfusion.ConclusionsDWIR is seen in up to a quarter of patients with acute ischemic stroke, and it is associated with good clinical outcome following reperfusion. Our findings highlight the pitfalls of DWI to define ischemic core in the early hours of stroke.

scholarly journals Diffusion-weighted imaging differentiates ischemic tissue from traumatized tissue.

Stroke ◽  
1994 ◽  
Vol 25 (4) ◽  
pp. 843-848 ◽  
Author(s):  
C C Hanstock ◽  
A I Faden ◽  
M R Bendall ◽  
R Vink
Keyword(s):  
Diffusion Weighted Imaging ◽  
Diffusion Weighted ◽  
Ischemic Tissue

Abnormalities of aquaporin-4 in the cerebellum in bipolar II disorder: An ultra-high b-values diffusion weighted imaging study

2020 ◽  
Vol 274 ◽  
pp. 136-143
Author(s):  
Lianping Zhao ◽  
Zhenye Luo ◽  
Shaojuan Qiu ◽  
Yanbin Jia ◽  
Shuming Zhong ◽  
...  
Keyword(s):  
Diffusion Weighted Imaging ◽  
Imaging Study ◽  
Aquaporin 4 ◽  
Bipolar Ii Disorder ◽  
B Values ◽  
Diffusion Weighted ◽  
Bipolar Ii

scholarly journals Role for Matrix Metalloproteinase 9 after Focal Cerebral Ischemia: Effects of Gene Knockout and Enzyme Inhibition with BB-94

2000 ◽  
Vol 20 (12) ◽  
pp. 1681-1689 ◽  
Author(s):  
Minoru Asahi ◽  
Kazuko Asahi ◽  
Jae-Chang Jung ◽  
Gregory J. del Zoppo ◽  
M. Elizabeth Fini ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Knockout Mice ◽  
Focal Cerebral Ischemia ◽  
Gene Knockout ◽  
Focal Ischemia ◽  
Lesion Size ◽  
Wild Type ◽  
Systemic Hemodynamic ◽  
Ischemic Lesion ◽  
Mmp Inhibitor

It has been shown recently that matrix metalloproteinases (MMPs) are elevated after cerebral ischemia. In the current study, we investigated the pathophysiologic role for MMP-9 (gelatinase B, EC.3.4.24.35) in a mouse model of permanent focal cerebral ischemia, using a combination of genetic and pharmacologic approaches, Zymography and Western blot analysis demonstrated that MMP-9 protein levels were rapidly up-regulated in brain after ischemic onset. Reverse transcription polymerase chain reaction showed increased transcription of MMP-9. There were no differences in systemic hemodynamic parameters and gross cerebrovascular anatomy between wild type mice and mutant mice with a targeted knockout of the MMP-9 gene. After induction of focal ischemia, similar reductions in cerebral blood flow were obtained. In the MMP-9 knockout mice, ischemic lesion volumes were significantly reduced compared with wild type littermates in male and female mice. In normal wild type mice, the broad spectrum MMP inhibitor BB-94 (batimastat) also significantly reduced ischemic lesion size, However, BB-94 had no detectable protective effect when administered to MMP-9 knockout mice subjected to focal cerebral ischemia. These data demonstrate that MMP-9 plays a deleterious role in the development of brain injury after focal ischemia.

scholarly journals Quantitative Measurement of Diffusion-weighted Imaging Signal Using Expression-controlled Aquaporin-4 Cells: Comparative Study of 2-compartment and Diffusion Kurtosis Imaging Models

2021 ◽  
Author(s):  
Akiko Imaizumi ◽  
Takayuki Obata ◽  
Jeff Kershaw ◽  
Yasuhiko Tachibana ◽  
Yoichiro Abe ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Water Permeability ◽  
Diffusion Weighted Imaging ◽  
Aquaporin 4 ◽  
Diffusion Kurtosis Imaging ◽  
Parameter Estimates ◽  
Aqp4 Expression ◽  
Diffusion Weighted ◽  
Diffusion Kurtosis ◽  
And Diffusion

Purpose: The purpose of this study was to compare parameter estimates for the 2-compartment (2Comp) and diffusion kurtosis imaging (DKm) models obtained from diffusion-weighted imaging (DWI) of aquaporin-4 (AQP4) expression-controlled cells, and to look for biomarkers that indicate differences in the cell membrane water permeability. Methods: DWI was performed on AQP4-expressing and non-expressing cells and the signal was analyzed with the 2Comp and DKm models. For the 2Comp model, the diffusion coefficients (Df, Ds) and volume fractions (Ff, Fs, Ff=1-Fs) of the fast and slow compartments were estimated. For the DKm model, estimates of the diffusion kurtosis (K) and corrected diffusion coefficient (D) were obtained. Results: For the 2Comp model, Ds and Fs showed clear differences between AQP4-expressing and non-expressing cells. Fs was also sensitive to cell density. There was no clear relationship with the cell type for the DKm parameters. Conclusions: Changes to cell membrane water permeability due to AQP4 expression affected DWI of cell suspensions. For the 2Comp and DKm models, Ds was the parameter most sensitive to differences in AQP4 expression.

Role of diffusion weighted imaging for differentiating cerebral pilocytic astrocytoma and ganglioglioma BRAF V600E-mutant from wild type

2019 ◽  
Vol 62 (1) ◽  
pp. 71-80
Author(s):  
Antonia Ramaglia ◽  
Domenico Tortora ◽  
Kshitij Mankad ◽  
Maarten Lequin ◽  
Mariasavina Severino ◽  
...  
Keyword(s):  
Pilocytic Astrocytoma ◽  
Diffusion Weighted Imaging ◽  
Braf V600e ◽  
Wild Type ◽  
Diffusion Weighted

scholarly journals Polynitroxyl Albumin Reduces Infarct Size in Transient Focal Cerebral Ischemia in the Rat: Potential Mechanisms Studied by Magnetic Resonance Imaging

1998 ◽  
Vol 18 (9) ◽  
pp. 1022-1031 ◽  
Author(s):  
Christian Beaulieu ◽  
Elmar Busch ◽  
Joachim Röther ◽  
Alexander de Crespigny ◽  
Carleton J. C. Hsia ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Cerebral Ischemia ◽  
Magnetic Resonance ◽  
Middle Cerebral Artery ◽  
Diffusion Weighted Imaging ◽  
Focal Cerebral Ischemia ◽  
Treated Group ◽  
Resonance Imaging ◽  
Diffusion Weighted ◽  
Transient Focal Cerebral Ischemia

Nitroxide free radicals are known to protect cells from oxidative damage. Diffusion-weighted and perfusion-weighted magnetic resonance imaging was used to evaluate the effects of polynitroxyl albumin(PNA) in a middle cerebral artery intraluminal suture model of transient focal cerebral ischemia in the rat. Three groups of Sprague-Dawley rats were investigated: (1) PNA(N = 6), (2) human serum albumin (N = 6), and (3) saline (N = 7). The middle cerebral artery was occluded for 2 hours. Treatment was started 30 minutes after induction of ischemia. A total dose of 1% body weight (volume/weight) of PNA (23.5 mg/dL protein and 110 mmol/L nitroxide), albumin (23.5 mg/dL), or saline was injected intravenously at three time points: 0.5% at 0.5 hours, 0.25% at 2 hours (i.e., just before reperfusion), and 0.25% at 4 hours after occlusion. Six sets of diffusion- and perfusion-weighted magnetic resonance images were acquired throughout the 2 hours of ischemia and the 2 hours of reperfusion. The rats were killed at 24 hours, and the brains were stained with 2,3,5-triphenyltetrazolium chloride (TTC). Diffusion-weighted imaging showed that the growth of the ischemic lesion was suppressed in the PNA-treated group. The 4 hours diffusion-weighted imaging-derived hemispheric lesion volume in the PNA-treated group (25% ± 9%) was significantly smaller than that in the saline-treated(43% ± 13%; P = 0.016) or albumintreated groups (38% ± 6%; P = 0.017). A larger difference was observed for the 24-hour TTC-derived lesion volumes in the PNA (8% ± 7%), saline (35% ± 8%; P< 0.001), and albumin (31% ± 6%; P < 0.001) groups. Perfusion-weighted imaging demonstrated a marked improvement in cerebral perfusion in the PNA-treated group during ischemia and reperfusion. In conclusion, treatment with PNA results in an improvement in perfusion and a reduction of infarct volume in a model of transient focal cerebral ischemia in the rat.

Characterizing the human APOE epsilon 4 knock-in transgene in female and male rats with multimodal magnetic resonance imaging

2020 ◽  
Author(s):  
Praveen Kulkarni ◽  
Simone Grant ◽  
Thomas Morrison ◽  
Xuezhu Cai ◽  
Sade Iriah ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Brain Structure ◽  
Resting State ◽  
Diffusion Weighted Imaging ◽  
Male Rats ◽  
Wild Type ◽  
Human Apoe ◽  
Diffusion Weighted ◽  
Male Carriers ◽  
Female Carriers

Abstract Background: The APOE Ɛ4 genotype is the most prevalent genetic risk for Alzheimer's disease (AD). Women carriers of Ɛ4 have higher risk for an early onset of AD than men. Human imaging studies suggest apolipoprotein E4 may affect brain structures associated with cognitive decline in AD many years before disease onset. It was hypothesized that female APOE Ɛ4 carriers would present with decreased cognitive function and neuroradiological evidence of early changes in brain structure and function as compared to male carriers. Methods: Six-month old wild-type (WT) and human APOE Ɛ4 knock-in (TGRA8960), male and female Sprague Dawley rats were studied for changes in brain structure using voxel-based morphometry, alteration in white and gray matter microarchitecture using diffusion weighted imaging with indices of anisotropy, and functional coupling using resting state BOLD functional connectivity. Images from each modality were registered to, and analyzed, using a 3D MRI rat atlas providing site-specific data on over 168 different brain areas. Results: Quantitative volumetric analysis revealed areas involved in memory and arousal were significantly different between Ɛ4 and wild-type (WT) females, with few differences between male genotypes. Diffusion weighted imaging showed few differences between WT and Ɛ4 females, while male genotypes showed significant different measures in fractional anisotropy and apparent diffusion coefficient. Resting state functional connectivity showed Ɛ4 females had greater connectivity between areas involved in cognition, emotion, and arousal compared to WT females, with male Ɛ4 showing few differences from controls. Interestingly, male Ɛ4 showed increased anxiety and decreased performance in spatial and episodic memory tasks compared to WT males, with female genotypes showing little difference across behavioral tests.Conclusion: The sex differences in behavior and diffusion weighted imaging suggest male carriers of the Ɛ4 allele may be more vulnerable to cognitive and emotional complications compared to female carriers early in life. Conversely, the data may also suggest that female carriers are more resilient to cognitive/emotional problems at this stage of life perhaps due to altered brain volumes and enhanced connectivity.

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