Interleukin-1beta does not affect the energy metabolism of rat organotypic hippocampal-slice cultures

The aim of this study was to examine the effect of the archetypal pro-inflammatory cytokine, interleukin-1beta (IL-1?), on high-energy phosphate levels within an ex vivo rat organotypic hippocampal-slice culture (OHSC) preparation using phosphorus ((31)P) magnetic resonance spectroscopy (MRS). Intrastriatal microinjection of IL-1? induces a chronic reduction in the apparent diffusion coefficient (ADC) of tissue water, which may be indicative of metabolic failure as established by in vivo models of acute cerebral ischaemia. The OHSC preparation enables examination of the effects of IL-1? on brain parenchyma per se, independent of the potentially confounding effects encountered in vivo such as perfusion changes, blood-brain barrier (BBB) breakdown and leukocyte recruitment. (31)P MRS is a technique that can detect multiple high-energy phosphate metabolites within a sample non-invasively. Here, for the first time, we characterise the energy metabolism of OHSCs using (31)P MRS and demonstrate that IL-1? does not compromise high-energy phosphate metabolism. Thus, the chronic reduction in ADC observed in vivo is unlikely to be a consequence of metabolic failure

Primula kisoana Miquel

原著和名: カッコサウ キソコザクラ科名: サクラソウ科 = Primulaceae採集地: 群馬県 鳴神山 (上野 鳴神山)採集日: 1963/5/5採集者: 萩庭丈壽整理番号: JH024269国立科学博物館整理番号: TNS-VS-97426

Additional file 3: Figure S3. of Astroglial NF-kB contributes to white matter damage and cognitive impairment in a mouse model of vascular dementia

Histological changes in the internal and external capsule. Reactive astrogliosis (A, E), microgliosis (B, F), axonal degeneration (C, G) and demyelination (D, H) in sham and BCAS animals in the internal capsule (upper row) and external capsule (lower row). (PDF 118 kb

CNS-Specific Synthesis of Interleukin 23 Induces a Progressive Cerebellar Ataxia and the Accumulation of Both T and B Cells in the Brain: Characterization of a Novel Transgenic Mouse Model.

peer reviewedInterleukin 23 (IL-23) is a key mediator in neuroinflammation in numerous autoimmune diseases including multiple sclerosis (MS). However, the pathophysiology of IL-23 and how it contributes to neuroinflammation is poorly defined. To further clarify the role of IL-23 in CNS inflammation, we generated a transgenic mouse model (GF-IL23) with astrocyte-targeted expression of both IL-23 subunits, IL-23p19, and IL-23p40. These GF-IL23 mice spontaneously develop a progressive ataxic phenotype, which corresponds to cerebellar tissue destruction, and inflammatory infiltrates most prominent in the subarachnoidal and perivascular space. The CNS-cytokine milieu was characterized by numerous inflammatory mediators such as IL-17a and IFNγ. However, the leukocytic infiltrates were surprisingly predominated by B cells. To further examine the impact of the CNS-specific IL-23 synthesis on an additional systemic inflammatory stimulus, we applied the LPS-induced endotoxemia model. Administration of LPS in GF-IL23 mice resulted in early and pronounced microglial activation, enhanced cytokine production and, in sharp contrast to control animals, in the formation of lymphocytic infiltrates. Our model confirms a critical role for IL-23 in the induction of inflammation in the CNS, in particular facilitating the accumulation of lymphocytes in and around the brain. Thereby, CNS-specific synthesis of IL-23 is able to induce a cascade of inflammatory cytokines leading to microglia activation, astrocytosis, and ultimately tissue damage. The presented transgenic model will be a useful tool to further dissect the role of IL-23 in neuroinflammation