Therapeutic potential of brain-derived neurotrophic factor and Schwann cells transplantation in experimental autoimmune neuritis

Abstract

Objective To investigate the therapeutic potential of brain-derived neurotrophic factor (BDNF) and Schwann cells (SCs) in experimental autoimmune neuritis (EAN) and assess the effect and mechanism. Methods EAN model was established by immunization of Lewis rats with 400μg of specific peptide P2(57-81)and complete Freund adjuvant.In the therapy group，the SCs (n=28) and the combination of BDNF administration and SCs (n=48) were labeled by the nuclear fluorescent dye injected into the intracerebroventricularly in 14 d after immunization.Transplanted cell migration tracking respectively were at 25，35 and 45 days after immunization.The rats were observed for signs of disease daily and subjected to clinical score，of which the sciatic nerves were subjected to histopathological examination (hematoxylin eosinstaining，luxol-fast-green and immunohistochemical staining).The inflammatory cell infiltration and demyelination were assessed，and the CD4，CD8，CD68，S-100 and nerve growth factor (NGF) positive cells numbers were compared among the 3 different groups. Results All the rats had the neurological deficits.Compared with control group，there were no significant differences in SCs therapy group.In SCs+ BDNF therapy group，the recovery of paralytic symptom was faster and the score was lower after immunization 45 d.After immunization 25 and 35 days，both the inflammatory cells infiltration (EAN model group: 325.8±10.8，221.4±35.2; SCs+BDNF transplantation group:307.3±4.6，197.2±16.8;t=2.172，P=0.031;t=3.756，P=0.000) and the expression of CD4+，CD8+T cells and CD68+ macrophages were reduced.After immunization 35，45 days，the demyelination degree (EAN model group:3.4±0.5，2.9±0.8;SCs+BDNF transplantation group:2.9±0.8，2.3±0.5) was reduced (t=-7.408，P=0.000;t=-6.092，P=0.000)，the expression of S-100 is higher，and NGF was lower than the control group in each time point after immunization. Conclusions SCs transplanted into the cerebellar ventricle of animals can migrate into the sciatic nerve.The combination of BDNF administration and SCs transplantation may represent an effective strategy by reducing inflammation reaction，improving the expression of S-100 in the donor cell，and reducing NGF irritability heighten in sciatic nerve.However，delivery of SCs alone is inefficiency to the treatment of EAN. Key words: Neuritis，autoimmune，experimental; Brain-derived neurotrophic factor; Schwann cells; Cell transplantation; Sciatic nerve