TY  - JOUR
A1  - Buga, Ana-Maria
A1  - Scholz, Claus Jürgen
A1  - Kumar, Senthil
A1  - Herndon, James G.
A1  - Alexandru, Dragos
A1  - Cojocaru, Gabriel Radu
A1  - Dandekar, Thomas
A1  - Popa-Wagner, Aurel
T1  - Identification of New Therapeutic Targets by Genome-Wide Analysis of Gene Expression in the Ipsilateral Cortex of Aged Rats after Stroke
JF  - PLoS One
N2  - Background: Because most human stroke victims are elderly, studies of experimental stroke in the aged rather than the young rat model may be optimal for identifying clinically relevant cellular responses, as well for pinpointing beneficial interventions. 
Methodology/Principal Findings: We employed the Affymetrix platform to analyze the whole-gene transcriptome following temporary ligation of the middle cerebral artery in aged and young rats. The correspondence, heat map, and dendrogram analyses independently suggest a differential, age-group-specific behaviour of major gene clusters after stroke. Overall, the pattern of gene expression strongly suggests that the response of the aged rat brain is qualitatively rather than quantitatively different from the young, i.e. the total number of regulated genes is comparable in the two age groups, but the aged rats had great difficulty in mounting a timely response to stroke. Our study indicates that four genes related to neuropathic syndrome, stress, anxiety disorders and depression (Acvr1c, Cort, Htr2b and Pnoc) may have impaired response to stroke in aged rats. New therapeutic options in aged rats may also include Calcrl, Cyp11b1, Prcp, Cebpa, Cfd, Gpnmb, Fcgr2b, Fcgr3a, Tnfrsf26, Adam 17 and Mmp14. An unexpected target is the enzyme 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 in aged rats, a key enzyme in the cholesterol synthesis pathway. Post-stroke axonal growth was compromised in both age groups. 
Conclusion/Significance: We suggest that a multi-stage, multimodal treatment in aged animals may be more likely to produce positive results. Such a therapeutic approach should be focused on tissue restoration but should also address other aspects of patient post-stroke therapy such as neuropathic syndrome, stress, anxiety disorders, depression, neurotransmission and blood pressure.
KW  - gamma
KW  - corticotropin-releasing hormone
KW  - colony-stimulating factor
KW  - cerebral ischemia
KW  - receptor
KW  - brain
KW  - protein
KW  - inhibitor
KW  - mouse
KW  - differentiation
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130657
VL  - 7
IS  - 12
ER  - 
TY  - JOUR
A1  - Nolte, Thomas
A1  - Zadeh-Khorasani, Maryam
A1  - Safarov, Orkhan
A1  - Rueff, Franziska
A1  - Varga, Rita
A1  - Herbach, Nadja
A1  - Wanke, Rüdiger
A1  - Wollenberg, Andreas
A1  - Mueller, Thomas
A1  - Gropp, Roswitha
A1  - Wolf, Eckhard
A1  - Siebeck, Matthias
T1  - Induction of oxazolone-mediated features of atopic dermatitis in NOD-scid IL2R \(γ^{null}\) mice engrafted with human peripheral blood mononuclear cells
JF  - Disease Models & Mechanisms
N2  - Animal models mimicking human diseases have been used extensively to study the pathogenesis of autoimmune diseases and the efficacy of potential therapeutics. They are, however, limited with regard to their similarity to the human disease and cannot be used if the antagonist and its cognate receptor require high similarity in structure or binding. Here, we examine the induction of oxazolone-mediated features of atopic dermatitis (AD) in NOD-scid IL2R \(γ^{null}\) mice engrafted with human peripheral blood mononuclear cells (PBMC). The mice developed the same symptoms as immunocompetent BALB/c mice. Histological alterations induced by oxazolone were characterized by keratosis, epithelial hyperplasia and influx of inflammatory cells into the dermis and epidermis. The cellular infiltrate was identified as human leukocytes, with T cells being the major constituent. In addition, oxazolone increased human serum IgE levels. The response, however, required the engraftment of PBMC derived from patients suffering from AD, which suggests that this model reflects the immunological status of the donor. Taken together, the model described here has the potential to evaluate the efficacy of therapeutics targeting human lymphocytes in vivo and, in addition, might be developed further to elucidate molecular mechanisms inducing and sustaining flares of the disease.
KW  - expression
KW  - model
KW  - pbl
KW  - differentiation
KW  - mechanisms
KW  - antagonists
KW  - gamma
KW  - human interleukin-4
KW  - rheumatoid-arthritis
KW  - T-cells
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-122189
VL  - 6
ER  -