PMID- 8965648 OWN - NLM STAT- MEDLINE DCOM- 19961203 LR - 20240109 IS - 0169-328X (Print) IS - 0169-328X (Linking) VI - 36 IP - 2 DP - 1996 Mar TI - Permeability at the blood-brain and blood-nerve barriers of the neurotrophic factors: NGF, CNTF, NT-3, BDNF. PG - 280-6 AB - A comparison was made of the permeabilities of different neurotrophic factors at the blood-brain barrier (BBB) and blood-nerve barrier (BNB) in normal adult rats by quantifying the permeability coefficient-surface area (PS) product after correction for the residual plasma volume (Vp) occupied by the protein in the capillary bed of the nerve endoneurium or different brain regions. The i.v. bolus injection technique was used in the cannulated brachial vein and artery using the same protein radioiodinated with a second isotope of iodine (125I vs. 131I) to separately determine the PS and Vp values. The plasma washout showed a decreasing plasma half-life in the order of brain-derived neurotrophic factor (BDNF) < neurotrophin-3 (NT-3) < ciliary neurotrophic factor (CNTF) < nerve growth factor (NGF). The PS at the BNB for NGF was 1.40 +/- 0.15 x 10(-6) ml/g/s (mean +/- SEM). The other neurotrophic proteins were all significantly higher than NGF (CNTF: 9.5 x ; NT-3: 20.8 x ; BDNF: 18.9 x ). The Vp for NGF at the BNB was 1.92 +/- 0.12 microliters/g and was not significantly different from the other proteins except for NGF vs. BDNF (P < 0.05). The PS for NGF at the BBB ranged from 1.5 to 2.7 x 10(-6) ml/g/s for six different brain regions. The PS for CNTF ranged from 6.0 to 8.0-fold higher than NGF; NT-3: 10.6 to 15.2-fold higher; and BDNF: 11.3 to 16.4-fold higher. The Vp values were not significantly different except for CNTF in the hippocampus and cortex (P < 0.05). SDS-PAGE analyses of all the radioiodinated neurotrophic proteins after 60 min of uptake revealed intact protein in the endoneurium and in the six different brain regions with exposure times of 2-42 days. The quantification of the permeability of these neurotrophic proteins provides baseline values for comparison of different protein modifications that enhance the PS while still preserving the neurotrophic activity (e.g., protein glycation; Poduslo and Curran, Mol. Brain Res., 23 (1994) 157). Enhanced permeability following modification might allow the use of systematic delivery of these proteins for practical therapeutic treatment of various neurodegenerative disorders. FAU - Poduslo, J F AU - Poduslo JF AD - Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA. FAU - Curran, G L AU - Curran GL LA - eng GR - NS 14304/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - Netherlands TA - Brain Res Mol Brain Res JT - Brain research. Molecular brain research JID - 8908640 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Ciliary Neurotrophic Factor) RN - 0 (Nerve Growth Factors) RN - 0 (Nerve Tissue Proteins) SB - IM MH - Animals MH - Autoradiography MH - Blood-Brain Barrier/*drug effects MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Ciliary Neurotrophic Factor MH - Male MH - Nerve Growth Factors/*pharmacology MH - Nerve Tissue Proteins/*pharmacology MH - Permeability/*drug effects MH - Rats MH - Rats, Sprague-Dawley MH - Time Factors EDAT- 1996/03/01 00:00 MHDA- 1996/03/01 00:01 CRDT- 1996/03/01 00:00 PHST- 1996/03/01 00:00 [pubmed] PHST- 1996/03/01 00:01 [medline] PHST- 1996/03/01 00:00 [entrez] AID - 0169328X9500250V [pii] AID - 10.1016/0169-328x(95)00250-v [doi] PST - ppublish SO - Brain Res Mol Brain Res. 1996 Mar;36(2):280-6. doi: 10.1016/0169-328x(95)00250-v.