A proposed role for nerve growth factor in the etiology of multiple sclerosis

Abstract

It is proposed that, in addition to genetic factors involved in immune attack on myelin, higher concentrations of nerve growth factor in certain tissues during development determine susceptibility to multiple sclerosis. High early nerve growth factor in some vasculature of spontaneously hypertensive rats increases sympathetic innervation and catecholamine production in these vessels. They become more sensitive than controls to noradrenaline after chemical sympathectomy. Continued exposure to high noradrenaline can result in sympathectomy-like effects, heightening sensitivity to constricting neurotransmitters. Vasoresponses of spontaneously hypertensive rats are impaired with submaximal but not maximal hypoxia. Such a situation in multiple sclerosis patients could result in insufficient blood flow by vasoconstriction until it becomes maximal. Glutamate increase by ischemia and hyperemic release of free radicals could injure neurons, prompting an immune response to myelin proteins in susceptible people. Developmental adaptation to situations requiring lower sympathetic activity might help counteract these effects.