Ultrastructural evidence of axonal shearing as a result of lateral acceleration of the head in non-human primates

Summary The concept of shearing of axons at the time of non-impact injury to the head was first suggested in the middle of this century. However, no experimental model of diffuse axonal injury (DAI) has provided morphological confirmation of this concept. Evidence from experiments on invertebrate axons suggests that membrane resealing after axonal transection occurs between 5 and 30 min after injury. Thus, ultrastructural evidence in support of axonal shearing will probably only be obtained by examination of very short-term survival animal models. We have examined serial thin sections from the corpus callosum of non-human primates exposed to lateral acceleration of the head under conditions which induce DAI. Tearing or shearing of axons was obtained 20 and 35 min after injury, but not at 60 min. Axonal fragmentation occurred more frequently at the node/paranode but also in the internodal regions of axons. Fragmentation occurred most frequently in small axons. Axonal shearing was associated with dissolution of the cytoskeleton and the occurrence of individual, morphologically abnormal membranous organelles. There was no aggregation of membranous organelles at 20 and 35 min but small groups did occur in some axons at 60 minutes. We suggest that two different mechanisms of injury may be occurring in non-impact injury to the head. The first is shearing of axons and sealing of fragmented axonal membranes within 60 min. A second mechanism occurs in other fibres where pertubation of the axon results in axonal swelling and disconnection at a minimum of 2 h after injury.Supported by NIH grant number NS-08803-21, the Wellcome Trust, the Royal Society, London and the Institute of Neurological Sciences, University of Glasgow. Part of this work was presented at the Ist International Neurotrauma Symposium, Fukishima, Japan and the IVth European Meeting of Neuropathology, Berlin Dedication: The authors would like this work to be a tribute to Professor J. H. Adams upon his retiral. His research into diffuse axonal injury inspired the authors to undertake this study.