METHODS:Oligodendrocyte apoptosis was induced in the adult rat brain using a lentivirus to express experimentally inducible caspase 9 (iCP9) cDNA under transcriptional control of the promoter for myelin basic protein, which is oligodendrocyte-specific. Activation of iCP9 was achieved by distal injection of a small molecule dimerizer into the lateral ventricle resulting in localized, acute oligodendrocyte apoptosis.
RESULTS. Induced oligodendrocyte apoptosis resulted in rapid demyelination and robust, localized microglial activation in the absence of peripheral immune cell infiltration. Lesion borders showed layers of preserved and degraded myelin, whereas lesion cores were demyelinated but only partially cleared of myelin debris. This resulted in local proliferation and mobilization of the oligodendrocyte progenitor pool.
INTERPRETATION: This approach provides a novel model to understand the pathological changes that follow from localized apoptosis of myelinating oligodendrocytes. It provides proof that initiation of apoptosis in oligodendrocytes is sufficient to cause rapid demyelination, gliosis, and a microglial response that result in lesions sharing some pathological characteristics with a subset of MS lesions.
This study looks what happens when oligodendrocytes are killed and find that demyelination occurs as has been shown in other reports. When the oligodencrocyte dies it causes demyelination and the activation of microglial cells. It is only days later that you get some T cells arriving. This may occur in MS see the "Charcot Tapestry". So this will be used by some as a reason about why T cells are not the central problem but as we have said before we can model this not into scenarios with autoimmunity and T cells