Cuprizone-induced demyelination in mice is a frequently used model in preclinical multiple sclerosis research. A recent quantitative clinically-targeted MRI method, fast macromolecular proton fraction (MPF) mapping demonstrated a promise as a myelin biomarker in human and animal studies with a particular advantage of sensitivity to both white matter (WM) and gray matter (GM) demyelination. This study aimed to histologically validate the capability of MPF mapping to quantify myelin loss in brain tissues using the cuprizone demyelination model. Whole-brain MPF maps were obtained in vivo on an 11.7T animal MRI scanner from 7 cuprizone-treated and 7 control С57BL/6 mice using the fast single-point synthetic-reference method. Brain sections were histologically stained with Luxol Fast Blue (LFB) for myelin quantification. Significant (p < 0.05) demyelination in cuprizone-treated animals was found according to both LFB staining and MPF in all anatomical structures (corpus callosum, anterior commissure, internal capsule, thalamus, caudoputamen, and cortex). MPF strongly correlated with quantitative histology in all animals (r = 0.95, p < 0.001) as well as in treatment and control groups taken separately (r = 0.96, p = 0.002 and r = 0.93, p = 0.007, respectively). Close agreement between histological myelin staining and MPF suggests that fast MPF mapping enables robust and accurate quantitative assessment of demyelination in both WM and GM.

A recent MRI method, fast macromolecular proton fraction (MPF) mapping, was used to quantify demyelination in the transient middle cerebral artery occlusion (MCAO) rat stroke model. MPF and other quantitative MRI parameters (T, T, proton density, and apparent diffusion coefficient) were compared with histological and immunohistochemical markers of demyelination (Luxol Fast Blue stain, (LFB)), neuronal loss (NeuN immunofluorescence), axonal loss (Bielschowsky stain), and inflammation (Iba1 immunofluorescence) in three animal groups ( n = 5 per group) on the 1st, 3rd, and 10th day after MCAO. MPF and LFB optical density (OD) were significantly reduced in the ischemic lesion on all days after MCAO relative to the symmetrical regions of the contralateral hemisphere. Percentage changes in MPF and LFB OD in the ischemic lesion relative to the contralateral hemisphere significantly differed on the first day only. Percentage changes in LFB OD and MPF were strongly correlated (R = 0.81, P < 0.001) and did not correlate with other MRI parameters. MPF also did not correlate with other histological variables. Addition of T into multivariate regression further improved agreement between MPF and LFB OD (R = 0.89, P < 0.001) due to correction of the edema effect. This study provides histological validation of MPF as an imaging biomarker of demyelination in ischemic stroke.

Remyelination is a key process enabling post-stroke brain tissue recovery and plasticity. This study aimed to explore the feasibility of demyelination and remyelination monitoring in experimental stroke from the acute to chronic stage using an emerging myelin imaging biomarker, macromolecular proton fraction (MPF). After stroke induction by transient middle cerebral artery occlusion, rats underwent repeated MRI examinations during 85 days after surgery with histological endpoints for the animal subgroups on the 7th, 21st, 56th, and 85th days. MPF maps revealed two sub-regions within the infarct characterized by distinct temporal profiles exhibiting either a persistent decrease by 30%–40% or a transient decrease followed by return to nearly normal values after one month of observation. Myelin histology confirmed that these sub-regions had nearly similar extent of demyelination in the sub-acute phase and then demonstrated either chronic demyelination or remyelination. The remyelination zones also exhibited active axonal regrowth, reconstitution of compact fiber bundles, and proliferation of neuronal and oligodendroglial precursors. The demyelination zones showed more extensive astrogliosis from the 21st day endpoint. Both sub-regions had substantially depleted neuronal population over all endpoints. These results histologically validate MPF mapping as a novel approach for quantitative assessment of myelin damage and repair in ischemic stroke.

Changes in liver structure in experimental CCl₄-induced hepatitis depend on the phase of the circumannual cycle. Pronounced disorders in the liver with a model of toxic hepatitis were observed in winter and fall and minor changes were recorded in summer. In spring, the liver was characterized by higher adaptation and compensatory potential, its structural status spontaneously returned to normal on day 4 after the last injection of CCl₄.

Цель. Сравнить морфологию, минеральный и органический профиль магний-фосфатных бионов (МФБ) и кальций-фосфатных бионов (КФБ) для оценки пригодности МФБ как группы сравнения с целью тестирования специфичности эндотелиотоксического действия КФБ.Материалы и методы. МФБ и КФБ были искусственно синтезированы посредством перенасыщения имитирующей состав крови среды солями магния и кальция соответственно. Морфологические свойства МФБ и КФБ были изучены при помощи электронной и атомно-силовой микроскопии, элементный состав -посредством энергодисперсионной рентгеновской спектроскопии, атомно-эмиссионной спектроскопии и CHNSO-анализа, функциональные группы -инфракрасной спектроскопией с преобразованием Фурье и спектроскопией комбинационного рас-сеяния света, формула входящих в состав бионов химических соединений -рентгеновской порошковой дифрактометрией. Белковый профиль МФБ и КФБ был исследован методом электрофореза в полиакриламидном геле с последующим окрашиванием нитратом серебра.Результаты. Как МФБ, так и КФБ представляли собой сферические частицы губчатой структуры диаметром 80-200 нм и средним диаметром около 120 нм, склонные к формированию кластеров из нескольких частиц. И МФБ, и КФБ состояли из углерода, кислорода, азота, водорода и фосфора, однако МФБ содержали магний и характеризовались минимальным содержанием кальция. МФБ и КФБ содержали фосфатные, карбонатные и гидроксильные группы, при этом МФБ состояли из магния фосфат гидрата и хантита, а КФБиз гидроксиапатита и карбонат-гидроксиапатита. Белковый профиль МФБ и КФБ был схожим.