Biomedical subjects

Ryszard Pluta

Publications and source records attributed to Ryszard Pluta.

9 recordsLinked to original sources

PubMed2006

Is the ischemic blood-brain barrier insufficiency responsible for full-blown Alzheimer's disease?

The goal of this paper is to provide scientists with a comprehensive review of the state-of-the-art influence the ischemic blood-brain barrier (BBB) has on the final development of Alzheimer's disease and to provide detailed food-for-thought which will hopefully stimulate more researchers in this area of neuroscience. Understanding new and fundamental concepts about the behavior of the BBB during long-term reperfusion after ischemia with a variety of new neuropathogenic factors can hopefully provide some interesting clues related to the pathologic processes issues that have been receiving considerable attention in the human clinic. We present the recent data to understand the role of the BBB in maturation of both diseases and try to differentiate between primary and secondary pathologic mechanisms. In conclusion, the neuropathogenesis of Alzheimer's disease involves an initial ischemic neuronal alterations leading to enhanced neuronal vulnerability to beta-amyloid peptide and the ischemic breakdown of the BBB with leakage of serum borne beta-amyloid peptide into brain parenchyma, activation of beta-amyloid peptide-dependent toxicity culminating in the formation of amyloid plaques and finally end in full-blown Alzheimer's disease. In summary, probably we have combined mechanism(s) of ischemia processes, ischemic and chronic BBB dysfunction and beta-amyloid peptide-dependent injury in pathology of neurodegeneration that is observed in Alzheimer's disease. We speculate that Alzheimer's disease may be caused by silent and sublethal ischemic episodes that attack and slowly steal the minds of its victims. Finally, our review proposes the ischemic BBB-dependent mechanism(s) that probably are responsible for full-blown Alzheimer's disease.

Alzheimer Disease↗

PubMed2005

Pathological opening of the blood-brain barrier to horseradish peroxidase and amyloid precursor protein following ischemia-reperfusion brain injury.

This study was performed to test the hypothesis that fragments of amyloid precursor protein are able to enter the injured blood-brain barrier (BBB) following brain ischemia. We observed chronic disruption of the BBB after ischemia. The BBB changes did not increase in intensity and frequency with longer periods of recirculation. As an effect of BBB injury, we noted a visible connection of diffuse amyloid plaques with neurovasculature in rats. This pathology appears to have a similar distribution as in Alzheimer's disease, hippocampal and cortical changes being most severe.

Alzheimer Disease↗

PubMed2004

Amyloid beta(1-42) and its beta(25-35) fragment induce activation and membrane translocation of cytosolic phospholipase A2 in bovine retina capillary pericytes.

We investigated changes in cytosolic phospholipase A(2) (cPLA(2)) and calcium-independent PLA(2) (iPLA(2)) activities in bovine retina capillary pericytes after stimulation with 50 microM amyloid-beta (Abeta) (1-42) and its (25-35) fragment, over 24 h (mild, sublethal model of cell damage). In the presence of Abeta peptides, we found that cPLA(2) activity was increased and translocated from the cytosolic fraction to the membrane system, particularly in the nuclear region. Reversed-sequence Abeta(35-25) peptide did not stimulate or induce cPLA(2) translocation. Exposure to both Abeta peptides had no significant effect on cPLA(2) protein content as tested by Western immunoblot analysis. The addition of Abetas to quiescent pericytes was followed by phosphorylation of cPLA(2) and arachidonic acid release. Treatment with inhibitors (AACOCF(3), staurosporine and cycloheximide) resulted in a sharp decrease in basal and stimulated cPLA(2) activity. Inactivating effects of bromoenol lactone (BEL), inhibitor of iPLA(2), demonstrated that the stimulation of total PLA(2) activity by Abetas was mediated by both PLA(2) enzymes. Taken together with our previous observations that both Abeta peptides may induce hydrolysis of phosphatidylcholine, the present results provide evidence that this process is cooperatively mediated by cPLA(2) activation/translocation and iPLA(2) activation. The effect is very likely triggered by a mild prooxidant mechanism which was not able to divert the cell to degeneration. The data confirm the hypothesis that pericytes could be a target of potential vascular damage and reactivity during processes involving amyloid accumulation.

Amyloid beta-Peptides↗

PubMed2004

From brain ischemia-reperfusion injury to possible sporadic Alzheimer's disease.

Understanding of the molecular basis of dementias such as Alzheimer's disease has not improved greatly in recent years. In this situation the study of neurobiology of Alzheimer's disease, now more than ever, needs an infusion of new concept. Recent evidence suggests that the neuropathological picture of Alzheimer's disease comprises more than amyloid accumulation, neurofibrillary tangles and finally brain atrophy. At least one third of Alzheimer type of dementia cases exhibit different cerebrovascular diseases. In addition, micro- and macro-infarctions and ischemic white matter changes are also evident in brains of Alzheimer's disease patients. The presence of vascular abnormalities seems usually ignored and regarded by researchers as insignificant or considered incidental in Alzheimer's disease etiology. The "ischemia-reperfusion hypothesis" was primarily aimed at stimulating research and redirecting the focus of studies towards ischemic cellular mechanisms of Alzheimer's disease. Considerable progress has been made in recent years in understanding the role of ischemia in the aging process and in contributing to the development of Alzheimer's disease. To accommodate the recent ischemic progress of study in Alzheimer's disease there is a need to synthesize all the divergent pieces of data into a coherent story. In this review, current knowledge on the relation between cerebrovascular disease factors and Alzheimer's type dementia will be reviewed. We will summarize the results with a special focus on Alzheimer lesions in experimental brain ischemia.

Alzheimer Disease↗

PubMed2004

Alzheimer lesions after ischemia-reperfusion brain injury.

For now the best-established and accepted theory in Alzheimer's disease (AD) etiology by most scientists is the "amyloid theory", as the main molecular factor of neurodegeneration in AD. We critically review these observations and highlight inconsistencies between the predictions of the "amyloid hypothesis" and the published data. The research of neurobiology of AD, now more than ever, needs an infusion of new concepts. Handful researchers now recognize brain ischemia as a prominent feature in AD and a potential target for therapy aimed at treatment and prevention of disease. The "ischemia-reperfusion theory" was primarily aimed at stimulating study and redirecting the focus of investigations towards ischemic cellular mechanisms of AD. To accommodate the recent progress of study in AD there is a need to synthesize all the divergent pieces of data into a coherent story. This review provides a synopsis of current information about ischemic cellular and molecular mediators involved in Alzheimer's neuropathology as well as interactions between these mediators that influence pathology. In this paper, current knowledge on the close relation between vascular disease factors and Alzheimer's type dementia will be reviewed. We will summarize the data with a special focus on Alzheimer lesions in experimental brain ischemia. Taken all together, evidence presented in this review suggests a scheme for Alzheimer's pathogenesis with ischemia playing a crucial role in influencing and linking beta-amyloid deposition to neuronal damage and clinical disease.

Alzheimer Disease↗

PubMed2003

Complications of a trophic xenotransplant approach in parkinsonian monkeys.

Various restorative cell transplantation strategies have been investigated to substitute for lost dopamine (DA) neurons or to enhance DA synthesis in Parkinson's disease. Intracerebral implantation of engineered cells encapsulated in a semipermeable polymer membrane constitutes one way to deliver bioactive substances unable to cross the blood-brain barrier while avoiding the need for long-term immunosuppression. Glial cell line-derived neurotrophic factor (GDNF) has shown trophic effects on DA neurons but effective and sustained delivery within the brain parenchyma remains problematic. The long-term efficacy and late complications of a xenotransplant approach utilizing GDNF-expressing encapsulated baby hamster kidney (BHK) cells were examined. Each of five MPTP-lesioned parkinsonian cynomolgus monkeys received five devices containing active or inert cells grafted bilaterally in the striatum in a two-stage procedure 9 months apart and animals were sacrificed 4 months later for analyses. No definite motor benefit was observed, DA levels were comparable between GDNF- and control cell-implanted striata, and tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra showed no consistent recovery. Cell viability and GDNF synthesis in the explanted devices were negligible. The brain tissue surrounding all implants showed an intense immune reaction with prominent "foreign body" inflammatory infiltrates. Membrane biophysics, the cell type used, and the extended period of time the devices remained in situ may have contributed to the negative outcome and should be addressed in future investigations using this approach.

Animals↗

PubMed2002

Glial expression of the beta-amyloid peptide in cardiac arrest.

We have investigated in the rat, immunocytochemically, the expression of beta-amyloid peptide in glial cells following ischemia-reperfusion brain injury. The postischemic brain injuries were studied at survival times from 2 days to 12 months. The reactive astrocytes with indirect staining for beta-amyloid peptide were observed in brain till 7 days postischemia. beta-Amyloid positive astrocytes disappeared transiently on the 14 days and then reappeared in the 6 months and again disappeared at 9 months after brain injury. Transient ischemia temporarily induced beta-amyloid peptide expression in reactive astrocytes, but this expression peaked at 7 days and 6 months. A glial appearance of beta-amyloid peptide direct staining occurred at a time when extensive neuronal loss was evident.

Amyloid beta-Peptides↗

PubMed2002

Astroglial expression of the beta-amyloid in ischemia-reperfusion brain injury.

Vascular damage and reactive gliosis are found colocalized with amyloid deposits in Alzheimer's disease brain, suggesting that the cerebrovasculature may be a clinically relevant site of Alzheimer's disease pathology and may contribute to the neurodegeneration process in Alzheimer's disease. In ischemic conditions, amyloid precursor protein and amyloid peptide are reported to be upregulated in neurons and in extracellular space. Expression and distribution of amyloid precursor protein and amyloid peptide in astroglial cells were examined immunohistochemically after 10-min cardiac arrest. After reperfusion for 2, 7, and 14 days and 1, 6, 9, and 12 months, brains were immunostained. The indirect reactive astrocytes with fragments of the full-length amyloid precursor protein were observed in brains until 7 days postischemia. Direct immunoreactivity only of amyloid peptide and the C-terminal of amyloid precursor protein was also localized in the reactive astrocytes in ischemic brains at 6 months after ischemia. Ischemia temporarily induced amyloid peptide overexpression in reactive astrocytes, but this expression peaked at 7 days and 6 months. A glial appearance of amyloid peptide and C-terminal of amyloid precursor protein staining occurred when extensive neuronal loss and the onset of brain atrophy were evident. The localization of the C-terminal of amyloid precursor protein within ischemic astroglial cells underscores the likely importance of the C-terminal of amyloid precursor protein in the pathogenesis of ischemia as in Alzheimer's disease.

Aging↗

PubMedDate not supplied

[Lactoferrin in the central nervous system].

Lactoferrin (LF) is a protein secreted by the tissues of ectodermal origin. Its structure is similar to transferrin. LF appeared to be multifunctional, but its main functions are connected with the natural defense system of mammals. The biological role and origin of LF within brain in normal and disease processes are as yet uncharted. LF expression is greatly upregulated during neurodegenerative disorders and in elderly brains. LF may exert an antiinflammatory function via its inhibitory effect on hydroxyl radical formation. By antioxydative properties, LF prevents DNA damage and consequently tumor formation in the CNS. Moreover, LF specifically transactivates the p53 tumor suppressor gene. LF suppresses distress perception via opioid mediated mechanism and prevents a decrease of the immune system activity caused by psychosocial stress. Furthermore, LF possibly modulates behavior in man and in animals.

Alzheimer Disease↗