MRC
Prof. Dr. Ryszard Pluta
Department of Neuropathology
Medical Research Centre
Polish Academy of Sciences
02-106 Warsaw
Pawinskiego 5 Str.
Poland
pluta@medres.cmdik.pan.pl, pluta@cmdik.pan.pl

-- The group members of Department of Neurodegenerative Disoredrs (Medical Research Centre, Polish Academy of Sciences) are experts in Poland in the broad field of experimental neurodegeneratoin and its treatment, with a main interest in animal brain ischemia. The Principal Investigator has studied for more than 25 years the neuropathology, neurophysiology, neurochemistry and therapy of brain ischemia-reperfusion injury. Using a broad multidisciplinary approach to the problem, therapeutical investigations of prostacyclin, nimodipine, APV and idebenone were investigated. We developed a model of complete brain ischemia in the rabbit which led to the successful resuscitation of the brain after 1 hour of brain ischemia. In an attempt to more accurately mimic the human condition of global brain ischemia, we have developed a new and unique chronic rat model of brain ischemia, induced by cardiac arrest. This model offers the possibility of studying the evolution of postischemic neurodegenerative encephalopathy, because animals can survive for long periods of time. Investigations of the neuropathology of ischemic brain have provided new data that ischemia may be involved in the etiology of Alzheimer’s disease. These data suggest that beta-amyloidogenesis may involve mechanisms that operate also in postischemic brain. Current research focuses on the neuropathological link between the ischemic brain and neurodegeneration of the Alzheimer type. We developed an immunization model for the prevention of amyloid deposition. Department have cooperation with the Neurology Research Unit which is one of the main reference centre for the neurodegenerative disorders in Poland. This unit focuses on Alzheimer’s disease and other dementias. We were partners in project founded by the European Community (Vth Framework) which was headed by Prof. K.-A. Hossmann from Max Planck Institute in Cologne. This project was about changes in genome after brain ischemia. 

- Department of Neurodegenerative Disorders – equipment. 
Our whole Institute has recently moved into a new building, and we have access to all necessary equipment to carry out the proposed work. The group has all the necessary facilities for animal experiments and runs laboratories for histopathology, histochemistry and electron microscopy. In addition we have 1 dark room, 1 cold room, 1 room for genetic analysis and 1 liquid nitrogen storage system.

Introduction, rationale and state of the art
-- To search for common pathological factors in ischemic brain and in Alzheimer’s disease, experiments will be carried out in pathophysiologically precisely described, clinically relevant brain ischemia model. Brain ischemia will be induced by cardiac arrest, followed by short- and long-term survival (Pluta et al., 1991). At the present no efficient therapy is available for ischemic dementia but there is increasing evidence that ischemic injury is possible trigger of Alzheimer’s disease. The innovative aspect of our proposal is the renunciation of all a priori mechanistic concepts for understanding of etiology of Alzheimer’s disease. Further analysis of common changes will focus on the mechanisms of action and on the possibility of pharmacological interventions. Using this approach we will first differentiate between those changes which are relevant and which are irrelevant to etiopathology of Alzheimer’s disease and then search for pharmacological interventions, which promote brain survival. To this purpose, an innovative interdisciplinary approach will be used that combines pathophysiological, electrophysiological, molecular biological and advanced imaging methodologies to differentiate between disease-relevant and disease-irrelevant alterations.

Plan
-- Progression of neuropathological changes will be assessed by immunohistochemistry of GFAP, amyloid precursor protein, apolipoproteins, presenilin, cytokines, alpha-synuclein, HSP, NGF and especially blood-brain barrier changes for toxic and untoxic components of blood serum and additionally we will look for neuronal network and behaviour changes.
--Pluta R, Lossinsky AS, Mossakowski MJ, Faso L, Wisniewski HM.: Reassessment of a new model of complete cerebral ischemia in rats. Method of induction of clinical death, pathophysiology and cerebrovascular pathology. Acta Neuropathol., 83, 1-11, 1991.

Prof. Ryszard Pluta (male) was graduated in Medicine in 1977. Student fellowship Charite Clinic, Humboldt University, Berlin (1975) and Department of Surgery, University of Cologne, Cologne (1976). PhD student Medical Research Centre, Polish Academy of Sciences (1978-1981). Scientific visitor Institute of General Reanimatology, Moscaw (1979). 1983 PhD Medical Research Centre, PAS. Postdoctoral, Laboratory of Neuropathology and Neuroanatomical Sciences, National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, USA (1986-1988) and Department of Pathological Neurobiology, NYS Institute for Basic Research in Developmental Disabilities, Staten Island, New York, USA (1988-1989). 1990/1991, 1993/1994, 1997 Visiting Professor NYS Institute for Basic Research. 1992 Associated Professor Thesis, Medical Research Centre, Warsaw. 1990-1997 Residency in Neurology, Medical Academy of Warsaw. Professional position: 2004- full professor at Department of Neurodegenerative Disorders, Medical Research Centre, PAS, Warsaw. 
He is the leader of the group with more than 28 years experience in the field of experimental brain ischemia; study of neuropathology and neurophysiology of ischemia, molecular mechanisms of neuronal death, analysis of genome changes after ischemia, treatment of ischemia with development autovaccintion against amyloid accumulation in neurodegeneration and possible involvement of ischemic mechanisms in development of Alzheimer’s disease. He was participated to one European and International project and published more than 100 scientific articles in national and international journals.

Dr. Marzena Ułamek ( MD, specialist in Neurology, female). She is in the field of clinical neurology and experimental brain ischemia.. Her main interest is in the study of dementia and neurodegeneraticve disorders, through clinical assessment and neuropsychological evaluation of patients. She was participated to one European and International project and published more than 10 scientific articles in national and international journals.

MB. Sławomir Januszewski (Graduated in Biology, male), has 30 years of experience in animal models of brain ischemia. He will coordinate all the experimental studies performed in our laboratory. He was participated to one European and International project and published more than 20 scientific articles in national and international journals.

References:

MRC1. R. Pluta.: Pathological opening of the blood-brain barrier to horseradish peroxidase and amyloid precursor protein following ischemia-reperfusion brain injury. Chemotherapy, 51, 223-226, 2005.

MRC2. R. Pluta.: From brain ischemia-reperfusion injury to possible sporadic Alzheimer’s disease. Curr. Neurovasc. Res., 1, 441-453, 2004.

MRC3- R. Pluta.: Alzheimer lesions after ischemia-reperfusion brain injury. Folia Neuropathol., 42, 181-186, 2004.

MRC4. CD. Anfuso, G. Assero, G. Lupo, A. Nicota, G. Cannavo, RP. Strosznajder, P. Rapisarda, R. Pluta, M. Alberghina.: Amyloid beta(1-42) and its beta(25-35) fragment induce activation and membrane translocation of cytosolic phospholipase A(2) in bovine retina capillary pericytes. Biochem. Biophys. Acta 1686, 125-138, 2004.

MRC5. R. Pluta.: Blood-brain barrier dysfunction and amyloid precursor protein accumulation in microvascular compartment following ischemia-reperfusion brain injury with 1-year survival. Acta Neurochir., (Suppl.) 86, 117-122, 2003.

MRC6. R. Pluta.: Astroglial expression of the beta-amyloid in ischemia-reperfusion brain injury. Ann. NY Acad. Sci., 977, 102-108, 2002.

MRC7. R. Pluta.: Glial expression of the beta-amyloid peptide in cardiac arrest. J. Neurol. Sci., 203-204, 277-280, 2002.

MRC8. G. Lupo, CD. Anfuso, G. Assero, RP. Strosznajder, M. Walski, R. Pluta, M. Alberghina.: Amyloid β (1-42) and its β (25-35) fragment induce in vitro phosphatidylcholine hydrolysis in bovine retina capillary pericytes. Neurosci. Lett., 303, 185-188, 2001.

MRC9. R. Pluta, A. Misicka, M. Barcikowska, S. Spisacka, AW. Lipkowski, S. Januszewski.: Possible reverse transport of β-amyloid peptide across the blood-brain barrier. Acta Neurochir., (Suppl.) 76, 73-77, 2000.

MRC10. R. Pluta.: No effect of anti-oxidative therapy on cerebral amyloidosis following ischemia-reperfusion brain injury. Folia Neuropathol., 38, 188-190, 2000.

MRC11. R. Pluta.: The role of apolipoprotein E in the deposition of β-amyloid peptide during ischemia-reperfusion brain injury. A model of early Alzheimer’s disease. Ann. NY Acad. Sci., 903, 324-334, 2000.

MRC12. Pluta R, Lossinsky  AS, Mossakowski MJ, Faso L, Wisniewski HM.: Reassessment of a new model of complete cerebral ischemia in rats. Method of induction of clinical death, pathophysiology and cerebrovascular pathology. Acta Neuropathol., 83, 1-11, 1991.