Study On Permeability Of The βNGF Across Blood-brain Barrier

Background: Nerve growth factor (NGF) is one of the most important bioacitive molecules of the netvous system and plays an important role in the viability of neurons, growth, differentiation and regeneration of neutocyte. Neonatal hypoxic-ischemic brain damage is a common disease of central nervous system in neonate with very c omplicated pathogenesis. Recent studies shown that nerve growth factor (NGF) can alleviate encephatatrophy and apotosis after hypoxic-ischemia, suggesting that NGF has some therapeutic effect on neonatal hypoxic-ischemic brain damage (HIBD). But there are differences in previous reports about the extent to which these problems limit CNS penetration. Most investigators have assumed that parental delivery of neurotrophins is an impractical route to exert effects in the degenerating CNS. However, the ability of the blood-borne neurothophin NGF and its subunit βNGF to enter the CNS was demonstrated by autoradiography. One route for the entry of blood-borne neurotrophins into the CNS could be by direct permeation through the BBB at the brain and spinal cord. Thus, in this study we examined βNGF-penetration into the CNS using radioiodinated βNGF in rats. Objective: Study on the permeability of β-nerve growth factors (NGF) through blood brain barrier (BBB) to provide scientific basis for research of β-NGF in clinical therapeutic application. Design: A completely randomized controlled experimental study. Setting and Materials: Forty eight of 70-80 days old healthy adult Wistar rats with body mass of 190-210g and sixtheen of 7days old Healthy postnatal Wistar rats with body mass of 14-16g, healthy half males and half females, provided by the Experimental Animal Center of Gao Xin medical of Chang Chun. Methods and Main Outcome Measures: The β-NGF was labeled with 125I, and specific activity of the labeled βNGF was 14.0585 uCi/ug. The adult rats were randomly divided into 6 groups: 5 min group,15 min group , 30 min group , 45 min group , 60min group, 1.5h group. The postnatal rats were randomly divided into 2 groups: Hypoxic model group and normal postnatal group, of which the animals where treated wich 125I-βNGF immediately after hypoxic through vein injection. The 125I-βNGF contents in serum,and brain of aduIt rats were measured by r scintillometer at 5min, 15min, 30min, 45min, lh andl. 5h after intravenous injection of 5ug/g 125I-βNGF. Compared with the content of 125I-βNGF in blood, 125I-βNGF content in brain achieved the peak leavel of it in blood at 30min injection. And the 125I-βNGF contents in serum, and brain of normal postnatal rats and hypoxic postnatal rats were measured by r scintillometer at the same time when 125I-βNGF contents in aduIt rats brain tissue achieved peak level. Data were input into computer by Excel software and managed by SAS software employed by the Department o00f Statistics, t test...