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Vulnerable Regions (vulnerable + regions)
Selected AbstractsOxidative stress activates a positive feedback between the ,- and ,-secretase cleavages of the ,-amyloid precursor proteinJOURNAL OF NEUROCHEMISTRY, Issue 3 2008Elena Tamagno Abstract Sequential cleavages of the ,-amyloid precursor protein cleaving enzyme 1 (BACE1) by ,-secretase and ,-secretase generate the amyloid ,-peptides, believed to be responsible of synaptic dysfunction and neuronal cell death in Alzheimer's disease (AD). Levels of BACE1 are increased in vulnerable regions of the AD brain, but the underlying mechanism is unknown. Here we show that oxidative stress (OS) stimulates BACE1 expression by a mechanism requiring ,-secretase activity involving the c- jun N-terminal kinase (JNK)/c- jun pathway. BACE1 levels are increased in response to OS in normal cells, but not in cells lacking presenilins or amyloid precursor protein. Moreover, BACE1 is induced in association with OS in the brains of mice subjected to cerebral ischaemia/reperfusion. The OS-induced BACE1 expression correlates with an activation of JNK and c- jun, but is absent in cultured cells or mice lacking JNK. Our findings suggest a mechanism by which OS induces BACE1 transcription, thereby promoting production of pathological levels of amyloid , in AD. [source] Immunohistochemical study of the expression of cytokines and nitric oxide synthases in brains of patients with dementia with Lewy bodiesNEUROPATHOLOGY, Issue 1 2003Omi Katsuse Regional expression of cytokines (IL-1,, TNF-,), inducible nitric oxide synthase (iNOS) and neuronal NOS (nNOS) was immunohistochemically investigated in the brains of patients with dementia with Lewy bodies (DLB), compared with those of patients with Alzheimer's disease (AD) and non-demented elderly persons. It has been reported that inflammatory responses by cytokines and oxygen free radicals such as nitric oxide (NO) are associated with damaged neurons, degenerative neurites or amyloid deposits in AD brains. In the present study, overexpression of IL-1,, TNF-, and iNOS was demonstrated in the amygdala, hippocampus, entorhinal and insular cortices of DLB brains, which are pathologically the most vulnerable regions in DLB brains as well as AD brains. In addition, some Lewy body (LB)-bearing neurons were involved by the processes of IL-1,- and TNF-,-positive microglia, and most extracellular LB were associated with the processes of TNF-,- and iNOS-positive astroglia. Glial involvement was also found around neuritic plaques and extracellular neurofibrillary tangles. In contrast, the expression of nNOS was reduced in the amygdala of DLB brains showing severe Lewy pathology. These findings suggest that cytokines and NO are significantly implicated in neuronal damage and death including LB formation in DLB brains. [source] Up-regulation of a growth arrest and DNA damage protein (GADD34) in the ischaemic human brain: implications for protein synthesis regulation and DNA repairNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 6 2004F. White GADD34 is a growth arrest and DNA damage inducible gene up-regulated in response to DNA damage, cell cycle arrest and apoptosis. It is thought that GADD34 may play a crucial role in cell survival in ischaemia. GADD34 expression was assessed immunohistochemically in post-mortem human hippocampal tissue obtained from patients surviving for defined periods (0,24 h; 24 h,7 days) after a cardiac arrest and in age-matched control subjects. In control brain, cytoplasm staining in GADD34 immunopositive cells was faint but present throughout the hippocampus and cortex. There was minimal change in GADD34 expression in the group surviving 0,24 h after cardiac arrest. However GADD34 immunostaining was markedly increased in selectively vulnerable regions in the 24 h,7 day survival group. Increased GADD34 staining was present in ischaemic neurones and in some morphologically normal neurones after cardiac arrest. Extensive ischaemic damage was found to correlate with elevated GADD34 immunostaining in the CA1 layer of the hippocampus (**P < 0.0016). In addition, GADD34 was found to colocalize with proliferating cell nuclear antigen in some neurones. The up-regulation of GADD34 in response to global ischaemia in the human brain plus its influence on protein synthesis and DNA repair suggests that this protein may have the potential to influence cell survival. [source] Exposure of non-target tissues in medical diathermyBIOELECTROMAGNETICS, Issue 1 2010N. Leitgeb Abstract With different prevalence in different regions, radio frequency (RF) electromagnetic fields (EMF) are widely used for therapeutic tissue heating. Although short-wave diathermy (27.12,MHz) is the most popular treatment modality, quantitative data on patient's exposure have been lacking. By numerical simulation with the numerical anatomical model NORMAN, intracorporal distributions of specific absorption rates (SAR) were investigated for different treatment scenarios and applicators. Quantitative data are provided for exposures of target treatment areas as well as for vulnerable regions such as the eye lenses, central nervous system, and testes. Different applicators and distances were investigated. Capacitive and inductive applicators exhibit quite a different heating efficiency. It could be shown that for the same output power therapeutic heat deposition can vary by almost one order of magnitude. By mimicking therapist's practice to use patient's heat perception as an indicator for output power setting, numerical data were elaborated demonstrating that muscle tissue exposures may be several times higher for inductive than for capacitive applicators. Presented quantitative data serve as a guide for power adjustment preventing relevant overexposures without compromising therapy; they also provide a basis for estimating target tissue heat load and developing therapeutic guidelines. Bioelectromagnetics 31:12,19, 2010. © 2009 Wiley-Liss, Inc. [source] | |||||||||||||