A major research area is the brain's innate immune cells, microglia, and the importance of these cells and infiltrating blood-borne macrophages in neuronal de- and regeneration in neurological disease. The neuroprotective and neurotoxic functions of these cells are studied using animal models of stroke, axonal injury and Alzheimer's disease. We have shown that the microglial response to injury is controlled by proliferation and apoptosis and that activated microglia through diverse cytokine production forms a heterogeneous cell population. We have also shown that microglia has important neuroprotective functions and that they through production of the multifunctional cytokine tumor necrosis factor improves the survival of neurons in the border zone of cerebral infarcts in mice. This observation contradicts the prevailing view that mikroglia solely has neurotoxic functions. Link 1
A closely related project focuses on the immune-glia-neuron interaction and remyelinisation that affect the course and symptomatology in patients with multiple sclerosis. In continuation of the above research on microglia, we have shown that the presence of myelin-reactive T cells in brain areas with axonal injury accentuates microglial response to the axonal injury and stimulates microglial phagocytosis of myelin debris. Since myelin debris has been shown to inhibit axonal growth and remyelinisation, we are currently investigating whether the presence of myelin-reactive T cells may also affect the formation and differentiation of the myelin forming oligodendrocytes. We in two parallel studies examine the effect of the clinically used drugs interferon-beta on microglial activation and oligodendrocyte differentiation, and aspects of transcriptional regulation of remyelination, using cuprizone-induced demyelinisation in mice as a model for multiple sclerosis. Link 2
Regarding method development, our research has set new standards for combining stereological techniques with immunocytochemistry and in situ hybridization. As something unique this opens up for quantitative studies of sub-populations of neurons and glia in the brain of both mouse and human. We are currently applying these techniques in studies of the cerebral cortex of neurologically normal deceased and of the glial reaction and neuronal death in the brains of deceased patients with neurological disease. Link 3
Our research group participates in the EU-funded project "Pre-clinical evaluation of human stem cells as therapy for stroke" and is a founding member of the EU-funded COST network "NEURINFNET" which deals with inflammation in neurological disease.