Effects of intracerebroventricular administration of NGF on blood brain barrier and stress induced protein in the central nervous system

ABSTRACT

Nerve growth factor [NGF] is the first member characterized of the neurotrophin family. It is known for its crucial role in survival, differentiation and maintenance of neurons both in peripheral and central nervous systems. In addition to its neurotropic role, NGF has also been proposed to act on cells of the immune system. Recent studies show that there is an increased level of NGF in cerebrospinal fluid [CSF] during the acute phase of multiple sclerosis, in animal model of multiple sclerosis and experimental allergic encephalomyelitis [EAE]. In contrast, during the remission phase of the diseases the levels of NGF drop significantly. More recently, the increased level of NGF has also been reported in other autoimmune diseases such as lupus erythematosus. These observations suggest that over production of NGF in CNS may functionally be related to the state of activation of the immune system in autoimmune diseases. Concomitantly, proinflammatory cytokines are upregulated in the acute phase of autoimmune diseases and are known to be potent inducers of the expression of heat shock proteins [HSP]. Moreover, NGF is known to be a chemotactic factor for polymorphonuclear cells [14, 15]. Due to concomitantly increased level of NGF in inflammatory sites and around the blood vessels in acute phase of the disease with leukocyte infiltration of the immune cells in CNS, one may question whether NGF has any effect on production of proinflammatory cytokines through production of heat shock proteins and leukocyte infiltration. To answer the above questions, NGF was injected intracerebroventricularly at doses 20 or 5 micro g/mice for 4 days. The results show that the administered NGF neither has any effect on the expression of HSP-27 nor on leukocyte infiltration in central nervous system, suggesting that the high doses of NGF utilized in these experiments affect neither the immune nor the central nervous systems