Alteration of excitatory neurotransmission is a key feature of
traumatic brain injury (TBI) in which extracellular
glutamate levels rise. Although increased synaptic release of
glutamate occurs at the injury site, the precise mechanism is unclear.
Complexin I and
complexin II constitute a family of cytosolic
proteins involved in the regulation of
neurotransmitter release, competing with the chaperone
protein alpha-SNAP (
soluble N-ethylmaleimide-sensitive factor-attachment protein) for binding to the synaptic vesicle
protein synaptobrevin as well as the synaptic membrane
proteins SNAP-25 and
syntaxin, which together form the
SNAP receptor (SNARE) complex.
Complexin I is predominantly a marker of axosomatic (inhibitory) synapses, whereas
complexin II mainly labels axodendritic and axospinous synapses, the majority of which are excitatory. In order to examine the role of these
proteins in TBI, we have studied levels of both complexins in the injured hemisphere by immunoblotting over a time period ranging from 6 h to 7 days following lateral fluid-percussion
brain injury in the rat. Transient increases in the levels of
complexin I and
complexin II proteins were detected in the injured cerebral cortex 6 h following TBI. This increase was followed by a decrease of
complexin I in the injured cortex and hippocampus, and a decrease in both complexins in the injured thalamus region at day 3 and day 7 post-injury. The early, transient increase in the injured cortex was completely blocked by
N-acetylcysteine (NAC) administered 5 min following
trauma, suggesting an involvement of oxidative stress. Neuronal loss was also reduced in the injured hemisphere with post-TBI NAC treatment. Our findings suggest a dysregulation of both inhibitory and excitatory neurotransmission following traumatic injury that is responsive to
antioxidant treatment. These alterations in complexin levels may also play an important role in neuronal cell loss following TBI, and thus contribute to the pathophysiology of cerebral damage following
brain injury.