An in vitro investigation was undertaken to study the roles of Na+ and Cl-
in mammalian spinal cord (SC) neuron deterioration and death after injury i
nvolving physical disruption of the plasma membrane. Individual SC neurons
in monolayer cultures were subjected to UV laser microbeam transection of a
primary dendrite. Neurons lesioned in modified ionic environments (MIEs) w
here 50%-75% of the NaCl was replaced with sucrose had higher survival (65%
-75%) than neurons lesioned in medium with normal (125 mM) NaCl (28%: p < 0
.001). Subsequent experiments found a comparable increase in lesioned neuro
n survival in MIEs in which only Na+ was replaced with specific ionic subst
itutes; however, replacement of Cl was not protective. Electron microscope
examinations of neurons fixed <16 min after lesioning showed a dramatic dec
rease in vesiculation of the smooth endoplasmic reticulum and Golgi apparat
us in the low NaCl or low Na+ MIEs. It is hypothesized that Na+ entry after
membrane disruption may stimulate elevation of [Ca+2]i leading to ultrastr
uctural disruption and death of injured neurons. The results of these studi
es suggest that a low NaCl MIE may be useful as an irrigant to limit damage
spread and cell death within CNS tissues during surgery or after trauma.