Neuro-inflammation, Neurotrophic Factors and Neuroprotection

PI: Ron Kooijman

 

Neuroprotection by administration of neurotrophic factors in animal models for ischemic stroke

Stroke is the most common cause of adult disability and ischemic stroke represents about 85% of all cases. Until now, only 10-15% of the patients benefit from the only approved treatment for ischemic stroke. We have provided proof-of-principle for neuroprotection by post-stroke systemic administration of recombinant human (rh)IGF-I or estradiol in a rat model of ischemic stroke. We address the basic mechanisms of neuroprotection by IGF-I and estradiol in ischemic stroke and are especially focussing on the role of microglia and neuroinflammation. Neuroinflammation is a common process in many neurological disorders and a common target for the development of new drugs. Neuroinflammation as a target for therapeutics is being investigated in collaboration with other projects at the C4N, e.g. the use of Ghrelin receptor antagonists in neurological disorders.

The role of astrocyte-neuronal interactions in multiple sclerosis

We will be building further on the finding that in Multiple Sclerosis lesions excessive amounts of the vasoconstrictor peptide endothelin-1 (ET-1) are produced by reactive astrocytes, which gives rise to cerebral hypoperfusion, enhanced blood-brain-barrier permeability, inflammatory reactions, excitotoxicity and astrogliosis. Counteracting these harmful effects of astrocytic ET-1 may represent a promising therapeutic approach for MS. We aim to decipher the mechanisms that underlie ET-1 overexpression in reactive astrocytes in this disease.