The majority of patients suffering from Alzheimer's disease (AD) demonstrate cerebral vascular changes and impaired regulation of cerebral blood flow, which has been assumed to play an important role in AD pathogenesis (vascular hypothesis of AD). There is strong evidence that both β-amyloid (Aβ) oligomers and plaques contribute to vascular injuries and functional impairments of the neurovascular unit. Vice versa, Aβ lesions can be triggered by hypertension and ischemic brain injury, while Aβ aggregates appear to have anti-angiogenic properties. Cholinergic dysfunction may result in impaired cerebral blood flow with consequences on normal function of the neurovascular unit including processing of the amyloid precursor protein (APP). To characterize in vivo the developmental relationship between Aβ formation and deposition, cortical cholinergic innervation and cerebrovascular abnormalities, transgenic Tg2576 mice that overexpress the Swedish double mutation of human APP, and demonstrate significant cerebral cortical deposition of Aβ plaques at ages from 9 months onwards, were considered as an appropriate animal model. Using the somatosensory cortex as a representative region, serial cryocut sections, were obtained from mice at ages ranging from 4 up to 18 months. These were subjected to immunohistochemistry to label vascular endothelial cells (anti-glucose transporter 1 (GluT1) immunostaining), cholinergic nerve terminals (anti-vesicular acetylcholine transporter (VAChT) immunostaining) and β-amyloid plaques (thioflavin S, and/or Solanum tuberosum lectin staining). This was followed by a thorough quantitative evaluation of the age-related spatial relationship between cerebral cortical capillaries, Aβ plaques and cholinergic terminals, using computer-assisted image analysis. The density of cholinergic terminals estimated by evaluation of VAChT immunohistochemistry in somatosensory cortical sections of wild type mice did not change with aging regardless of the cortical layer examined, while in cortical layers II/III and IV of somatosensory cortex of transgenic Tg2576 mice age-related decreases in cholinergic fiber densities were assessed. However, quantitative morphometric analysis demonstrated an age-related reduction in the number of varicosities on cholinergic fibers, particularly in layer IV, in both transgenic Tg2576 mice and non-transgenic littermates. Cholinergic innervation of microvessels in the somatosensory cortex decreased with aging in both Tg2576 mice and non-transgenic littermates, as revealed by estimating the ratio of the number of cholinergic vascular contacts and total length of blood vessel. There was no significant difference in the perivascular cholinergic innervation in areas that demonstrated significant plaque load and those with no plaque deposits regardless of the cortical layer examined. The density of blood vessels estimated in the somatosensory cortex of transgenic mice by anti-GluT-1 immunohistochemistry did not differ to that obtained in wild type mice before the onset of plaque depos...

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Considering a stage of the pathological process patients (boys at the age of 8-12 years) were divided into two (2) groups. Group I included 14 patients with the fragmentation stage (Perthes disease Stage II). Group 2 included 15 children with Perthes disease Stage III (the stage of re-ossification). Perthes disease regardless of the stage of the disease was characterized by the increase in oxygen-dependent and lysosomal phagocytic activity of neutrophils, the increase in the number of early extracellular traps, as well as by increased concentrations of pro-inflammatory cytokines (IL-1β and TNFa), IgE, decreased concentrations of IL-18. The fragmentation stage was characterized by moderate activation of cellular immunity with a prevailing increase in the number of T-lymphocytes with early activation markers (CD25). At the re-ossification stage the predominance of T-lymphocytes was observed with late activation markers (HLADR), being accompanied by moderate activation of humoral immunity (increased concentrations of class A and G serum immunoglobulins). The obtained data can be used as additional criteria for clarifying Perthes disease stage, predicting osteonecrosis development when making decision of the feasibility of performing reconstructive surgeries on the joint.