The multi-faceted basis of vitamin B12 (cobalamin) neurotrophism in adult central nervous system: Lessons learned from its deficiency

Glial cells, myelin and the interstitium are the structures of the mammalian central nervous system (CNS) mainly affected by vitamin B₁₂ (cobalamin, Cbl) deficiency. Most of the response to the damage caused by Cbl deficiency seems to come from astrocytes and microglia, and is manifested as an increase in the number of cells positive for glial fibrillary acidic protein, the presence of ultrastructural signs of activation, and changes in cytokine and growth factor production and secretion. Myelin damage particularly affects the lamellae, which are disorganized by edema, as is the interstitium. Surprisingly, rat Schwann cells (myelin-forming cells of the peripheral nervous system) are fully activated but the few oligodendrocytes (myelin-forming cells of the CNS) are scarcely activated. The presence of intramyelin and interstitial edema raises questions about the integrity of the blood–brain barrier and blood–cerebrospinal fluid (CSF) barrier.