After years of doubt and “darkness”, researchers from the University of Stanford (Palo Alto, California) have finally come up with an explanation on “chemo brain”, i.e. on cognitive disorders – especially loss of memory and concentration problems – often triggered by oncological chemotherapy (chemo brain, which patients describe as a kind of fogginess, generally vanishes several weeks after the end of treatment, but sometimes can go on for months or even years, with debilitating effects). The US researchers concentrated their efforts, in particular, on disorders linked to methotrexate, a chemotherapeutic drug commonly used to fight various kinds of tumors (leukaemia, and breast, lung and bladder cancer), and they realized that this drug tends to damage, or even destroy, oligodendrocyte precursor cells (abbreviated as OPCs), i.e. the brain cells required for the management of myelin (the protective sheath around nerve tissue). Without OPCs, “dysfunctions” are created, which may result in cognitive disorders.
But why does methotrexate, which is produced for entirely different purposes, end up damaging OPCs? And why do these cells, which normally reform quickly, get blocked instead? As explained by the Californian researchers in the scientific journal Cell, the mechanism of action is complex. It has been discovered that methotrexate, a toxic substance by definition, causes the extremely powerful activation of the so-called microglia (formed by cells of the defence system of the brain, which make up to 10% of brain matter and that usually act in response to a trauma or, indeed, a toxic substance). When these microglia are “activated” by methotrexate, they create a hostile environment, and a number of other effects, which make it difficult for oligodendrocytes to grow, and consequently results in the damage to cognitive abilities.
At this point researchers suggest that it is necessary to concentrate on the microglia in order to avoid these losses in cognitive ability. Various drugs aimed specifically at reducing the action of these cells are currently being studied. The drug that proves that it can work best will become the first effective substance against chemo brain and in general a good neuroprotector, at least against the damage caused by methotrexate.
