Quantitative method for detection of blood-nerve barrier alterations in experimental animal models of neuropathy

A solid phase radioimmunoassay was developed for measuring albumin concentrations in both endoneurium and serum, which were normalized to total endoneurium and serum protein to obtain a blood-nerve barrier index (BNB-index). The BNB-index in experimental lead neuropathy demonstrated barrier dysfunction beginning at 6 weeks of 4% lead carbonate ingestion and at 14 weeks was 5.2 times that of pair-fed controls. These data, therefore, confirmed investigations that indicated a gradual alteration of the BNB beginning at 6 weeks and were based on (i) direct measurement of endoneurial albumin concentration by densitometry after sodium dodecyl sulfate-pore gradient electrophoresis and (ii) intravenous injection of 125I-albumin (J. F. Poduslo, P. A. Low, A. J. Windebank, P. J. Dyck, C. T. Berg, and J. D. Schmeltzer, 1982. J. Neurosci. 2: 1507-1514). The BNB-index after crush injury was 2.2 times that of control nerves at 24 h and gradually decreased toward normal values but was still 1.6 times that of controls at 70 days, a value consistent with the prolonged time course for complete repair. The BNB-index, therefore, can be used to evaluate BNB alterations quantitatively in animal models of neuropathy. Furthermore, we suggest that the BNB-index can also be used on biopsied, neuropathic, human sural nerve for evaluation of blood-nerve barrier abnormality.