Regeneration of Lesioned Septohippocampal Acetylcholinesterase‐positive Axons is Improved by Antibodies Against the Myelin‐associated Neurite Growth Inhibitors NI‐35/250

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Abstract
Two oligodendrocyte membrane proteins, NI-35 and NI-250, have been shown to be highly inhibitory for neurite growth. Upon neutralization of these components with the specific monoclonal antibody IN-1, lesioned corticospinal tract fibres were able to regenerate over long distances. In the present study, we have investigated the behaviour of regenerating cholinergic septohippocampal tract fibres. Large fimbria/fornix aspiration lesions were bridged by human amnion extracellular matrix material containing nerve growth factor, and the inhibitor-neutralizing antibody IN-1 or a control antibody were applied. After 3 - 5 weeks survival time, acetylcholinesterase (AchE)-positive fibres had crossed the bridge and, upon entering the hippocampus, had developed a profuse fibre plexus. In the controls (antibody against peroxidase) the fibre growth within the hippocampal tissue remained limited to maximally 1 mm in the caudal and lateral directions. In the presence of the antibody IN-1, however, AchE-positive fibres were seen to grow for 2 - 4 mm both in the caudal and lateral directions. Interestingly, the regenerated fibres preferably grew to their original terminal areas in the infra- and suprapyramidal layers of the hippocampus proper and the hilus, and in the supragranular layer of the dentate gyrus. These data show that the neurite growth inhibitors severely impede regenerative axon growth also for the cholinergic fibres in the hippocampus, and that their neutralization increases axon growth and leads to partial reconstitution of the original anatomical fibre distribution.