Neuronal survival or death after dendrite transection close to the perikaryon: correlation with electrophysiologic,...

We investigated the probability of survival of mouse spinal neurons in monolayer cultures after transection lesions of dendrites made within 400 microns of the perikarya. Based on a total of 650 lesioned neurons, the following observations were made. First, neuronal survival is a function of lesion distance from the perikaryon and of process diameter at the lesion site. For an average lesion diameter of 3 microns, dendrite transections at 50 microns, 100 microns, and 150 microns were associated with survival probabilities of 30%, 53%, and 70%, respectively. Second, the fate of the injured cells was definitely established 24 hours after injury and very likely was determined as early as 2 hours. Third, early stages of deterioration leading to cell death were associated with cytoplasmic phase brightness on light microscopy, correlating with an appearance of numerous, small, electron-lucent vacuoles and swollen mitochondria on electron microscopy. The cytoplasm of these moribund cells stained darkly and contained no visible microtubules or neurofilaments. Fourth, the magnitude and time course of injury potentials recorded at the somata were a function of the lesion distance and did not return to prelesion levels within 30 minutes after transection. Fifth, at 24 hours after injury, the average membrane potential of lesioned neurons was 8% below that of control neurons. Sixth, at a lesion distance of approximately 300 microns both the injury potential and the probability of cell death approach zero. We conclude that, in the model system used, neuronal survival after dendrite amputation depends on physical parameters of the lesion that determine the magnitude of the injury current reaching the soma. Survival is not assured if the injury is inflicted within 250 microns of the cell body, and cell death is likely for lesions within 50 microns of the soma. The below-normal membrane potentials at 24 hours after injury suggest a possible greater vulnerability of recovering neurons to secondary insults. The characteristic mitochondrial disruption and loss of microtubules implies that the calcium component of the injury current contributes to cell death.