EFFECTS OF MAST-CELL DEGRANULATION ON BLOOD-NERVE BARRIER PERMEABILITY AND NERVE-CONDUCTION IN-VIVO

Changes in blood-nerve barrier (BNB) integrity and nerve conduction we re assessed in rat tibial nerves in which mast cell degranulation was induced by intraneural injection of Compound 48/80 (C48/80). BNB perme ability changes were quantitated by the endoneurial accumulation of Ev an's blue-labelled albumin (EBA). Over 24 h following intraneural inje ctions, nerves receiving saline showed a 6-fold increase in endoneuria l extravasated EBA compared to non-injected nerves. Injection of 250 n g C48/80 produced a similar level of EBA accumulation as saline inject ions. Increasing the C48/80 dose to 1 mu g produced twice the EBA accu mulation as control saline injections and a 12-fold increase over non- injected nerves. Tibial nerves injected with these C48/80 doses showed completely normal nerve conduction. In contrast, increasing the dose to 5 mu g C48/80 induced, again, increased EBA accumulation over lower doses, but also significant axonal degeneration indicated by profound decreases in compound muscle action potential amplitudes measured wit h nerve stimulation distal to the injection site. Co-injection of Leup eptin and neutralizing anti-TNF-alpha antibodies with C48/80 failed to mitigate conduction abnormalities suggesting a direct toxic effect of C48/80 on nerve fibres. Time-kinetic studies showed rapid restoration of BNB integrity 24-48 h after injections in all nerves, but at these timepoints C48/80 injected nerves still showed significantly increase d BNB permeability compared to nerves injected with saline. Neural mas t cell stimulation in the absence of a primed immune response can prod uce profound temporary changes in blood-nerve barrier permeability and endoneurial fluid composition without affecting nerve conduction.