Dataset Information

Phosphodiesterase III inhibition promotes differentiation and survival of oligodendrocyte progenitors and enhances regeneration of ischemic white matter lesions in the adult mammalian brain.

ABSTRACT: Vascular dementia is caused by blockage of blood supply to the brain, which causes ischemia and subsequent lesions primarily in the white matter, a key characteristic of the disease. In this study, we used a chronic cerebral hypoperfusion rat model to show that the regeneration of white matter damaged by hypoperfusion is enhanced by inhibiting phosphodiesterase III. A rat model of chronic cerebral hypoperfusion was prepared by bilateral common carotid artery ligation. Performance at the Morris water-maze task, immunohistochemistry for bromodeoxyuridine, as well as serial neuronal and glial markers were analyzed until 28 days after hypoperfusion. There was a significant increase in the number of oligodendrocyte progenitor cells in the brains of patients with vascular dementia as well as in rats with cerebral hypoperfusion. The oligodendrocyte progenitor cells subsequently underwent cell death and the number of oligodendrocytes decreased. In the rat model, treatment with a phosphodiesterase III inhibitor prevented cell death, markedly increased the mature oligodendrocytes, and promoted restoration of white matter and recovery of cognitive decline. These effects were cancelled by using protein kinase A/C inhibitor in the phosphodiesterase III inhibitor group. The results of our study indicate that the mammalian brain white matter tissue has the capacity to regenerate after ischemic injury.

SUBMITTER: Miyamoto N

PROVIDER: S-EPMC2949130 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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Phosphodiesterase III inhibition promotes differentiation and survival of oligodendrocyte progenitors and enhances regeneration of ischemic white matter lesions in the adult mammalian brain.

Miyamoto Nobukazu N Tanaka Ryota R Shimura Hideki H Watanabe Terubumi T Mori Hideo H Onodera Masafumi M Mochizuki Hideki H Hattori Nobutaka N Urabe Takao T

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20091014 2

Vascular dementia is caused by blockage of blood supply to the brain, which causes ischemia and subsequent lesions primarily in the white matter, a key characteristic of the disease. In this study, we used a chronic cerebral hypoperfusion rat model to show that the regeneration of white matter damaged by hypoperfusion is enhanced by inhibiting phosphodiesterase III. A rat model of chronic cerebral hypoperfusion was prepared by bilateral common carotid artery ligation. Performance at the Morris w ...[more]

PMID: 19826432

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Project description:Background: White matter lesions (WML) have been proved to be significantly associated with many brain diseases. Precise evaluation of burden of WML at early stage could provide insights in the prognosis and assist in intervention. However, acute ischemic lesions (AIL) exhibit hyperintensities on FLAIR images either, and are detected by diffusion weighted imaging (DWI). It is challenging to identify and segment WML in the patients with WML and AIL. Convolutional neural network (CNN) based architecture has been validated as an efficient tool for automatic segmentation. This study aimed to evaluate the performance of U-net in evaluation of WML in the patients with WML and AIL. Methods: A total of 208 cases from Chinese Atherosclerosis Risk Evaluation (CARE II) study were recruited in the present study. All subjects underwent imaging of FLAIR and DWI on 3.0 Tesla scanners. The contours of WML delineated by the observer and its scores rated by the observer were considered as gold standard. Among all 208 cases, 108 were randomly selected as train set, and the remaining 100 cases were used as test set. The performance of lesion segmentation toolbox (LST) and three U-net models were evaluated on three levels: pixel, lesion, and subject levels. The performance of all methods in WML identification and segmentation was also evaluated among the cases with different lesion volumes and between the cases with and without AIL. Results: All U-net models outperformed LST on pixel, lesion, and subject levels, while no differences were found among three U-net models. All segmentation methods performed best in the cases with WML volume (WMLV) > 20 ml but worst in those with WMLV < 5 ml. In addition, all methods showed similar performance between the cases with and without AIL. The scores determined by U-net exhibited a strong correlation with the gold standard (all Spearman correlation coefficients >0.89, ICCs >0.88, p-values <0.001). Conclusion: U-net performs well on identification and segmentation of WML in the patients with WML and AIL. The performance of U-net is validated by a dataset of multicenter study. Our results indicate that U-net has an advantage in assessing the burden of WML in the patients suffered from both WML and AIL.

Project description:BackgroundCerebral white matter lesions (WMLs) have been associated with a greater risk of poor functional outcome after ischemic stroke. We assessed the relations between WML burden and radiological and clinical outcomes in patients treated with endovascular treatment in routine practice.MethodsWe analyzed data from the MR CLEAN Registry (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischaemic Stroke in the Netherlands)-a prospective, multicenter, observational cohort study of patients treated with endovascular treatment in the Netherlands. WMLs were graded on baseline noncontrast computed tomography using a visual grading scale. The primary outcome was the score on the modified Rankin Scale at 90 days. Secondary outcomes included early neurological recovery, successful reperfusion (extended Thrombolysis in Cerebral Infarction ≥2b), futile recanalization (modified Rankin Scale score ≥3 despite successful reperfusion), and occurrence of symptomatic intracranial hemorrhage. We used multivariable logistic regression models to assess associations between WML severity and outcomes, taking the absence of WML on noncontrast computed tomography as the reference category.ResultsOf 3180 patients included in the MR CLEAN Registry between March 2014 and November 2017, WMLs were graded for 3046 patients and categorized as none (n=1855; 61%), mild (n=608; 20%), or moderate to severe (n=588; 19%). Favorable outcome (modified Rankin Scale score, 0-2) was achieved in 838 patients (49%) without WML, 192 patients (34%) with mild WML, and 130 patients (24%) with moderate-to-severe WML. Increasing WML grades were associated with a shift toward poorer functional outcome in a dose-dependent manner (adjusted common odds ratio, 1.34 [95% CI, 1.13-1.60] for mild WML and 1.67 [95% CI, 1.39-2.01] for moderate-to-severe WML; Ptrend, <0.001). Increasing WML grades were associated with futile recanalization (Ptrend, <0.001) and were inversely associated with early neurological recovery (Ptrend, 0.041) but not with the probability of successful reperfusion or symptomatic intracranial hemorrhage.ConclusionsAn increasing burden of WML at baseline is associated with poorer clinical outcomes after endovascular treatment for acute ischemic stroke but not with the probability of successful reperfusion or symptomatic intracranial hemorrhage.

Dataset Information

Phosphodiesterase III inhibition promotes differentiation and survival of oligodendrocyte progenitors and enhances regeneration of ischemic white matter lesions in the adult mammalian brain.

Publications

Phosphodiesterase III inhibition promotes differentiation and survival of oligodendrocyte progenitors and enhances regeneration of ischemic white matter lesions in the adult mammalian brain.

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