Search

We are currently witnesses to and authors of a paradigm shift in neuropathology. While classical acute and chronic neuroinflammatory diseases such as meningitis or multiple sclerosis (MS) present aspects of neurodegeneration, the disease course of progressive degenerative disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), or stroke-mediated neuronal deficit are demonstrably affected by inflammation. These insights have immediate consequences both for research methods and for the development of novel, more efficient therapies for these diseases. In this review, we analyze the inflammatory and degenerative pathological mechanisms in the brain with particular emphasis on the classical chronic inflammatory disease MS. We demonstrate that the latest pathological considerations not only require the application of advanced research technologies to investigate new pathomechanistic pathways, but also affect the investigation, development, and monitoring of novel potential therapeutic tools. [ABSTRACT FROM AUTHOR]

Inflammatory reactions in the CNS, resulting from a loss of control and involving a network of non-neuronal and neuronal cells, are major contributors to the onset and progress of several major neurodegenerative diseases. Therapeutic strategies should therefore keep or restore the well-controlled and finely-tuned balance of immune reactions, and protect neurons from inflammatory damage. In our study, we selected plants of the Malaysian rain forest by an ethnobotanic approach, and investigated them in cell-based-assay-systems and in living brain tissue cultures in order to identify anti-inflammatory and neuroprotective effects. We found that extracts from the tropical plant Knema laurina (Black wild nutmeg) exhibited highly antiinflammatory and neuroprotective effects in cell culture experiments, reduced NO- and IL-6-release from activated microglia cells dose-dependently, and protects living brain tissue from microglia-mediated inflammatory damage. On the intracellular level, the extract inhibited ERK-1/2-phosphorylation, I-kappaB-phosphorylation and subsequently NF-kappaB-translocation in microglia cells. Knema laurina belongs to the family of Myristicaceae, which have been used for centuries for treatment of digestive and inflammatory diseases and is also a major food plant of the Giant Hornbill. Moreover, extract from Knema laurina promotes also neurogenesis in living brain tissue after oxygen-glucose deprivation. In conclusion, extract from Knema laurina not only controls and limits inflammatory reaction after primary neuronal damage, it promotes moreover neurogenesis if given hours until days after stroke-like injury in levels comparable to the best neurotrophic factors known today. [ABSTRACT FROM AUTHOR]