W. Cho

Evolution of post-traumatic neurodegeneration after controlled cortical impact traumatic brain injury in mice and rats as assessed by the de Olmos silver and fluorojade staining methods.

This report documents an analysis of post-traumatic neurodegeneration during the first 7 days after controlled cortical impact (CCI) traumatic brain injury (TBI) in mice and rats using the de Olmos aminocupric silver staining method, which selectively stains degenerating axons and nerve terminals, compared to the fluorojade method, which stains degenerating neuronal cell bodies. A progressive increase in cortical, hippocampal, and thalamic degeneration was observed over the first 48 h after injury in both species. Approximately 50% of the ipsilateral cortical volume was stained at 48 h. Similarly, the dorsal hippocampus showed widespread degeneration in all of the subfields. This included CA1, CA3, CA4, and dentate cell bodies revealed by fluorojade together with a high degree of axonal degeneration in areas carrying afferent and efferent hippocampal projections that is identified by silver staining. These results show that previous CCI studies which have relied on conventional histological methods that show cell body staining alone have underestimated the degree of axonal damage associated with the CCI-TBI model. In order to capture the full extent of the injury to both axons and cell bodies, the combination of silver staining and fluorojade staining is needed, respectively. Future studies of potential neuroprotective agents should probably not rely on the measure of cortical lesion volume or volume of spared cortical tissue using conventional histological stains alone, since these fail to identify the complete extent of the posttraumatic neuropathology that some agents which reduce cortical lesion volume may not be able to effect.

Selective death of newborn neurons in hippocampal dentate gyrus following moderate experimental traumatic brain injury

Memory impairment is one of the most significant residual deficits following traumatic brain injury (TBI) and is among the most frequent complaints heard from patients and their relatives. It has been reported that the hippocampus is particularly vulnerable to TBI, which results in hippocampus‐dependent cognitive impairment. There are different regions in the hippocampus, and each region is composed of different cell types, which might respond differently to TBI. However, regional and cell type‐specific neuronal death following TBI is not well described. Here, we examined the distribution of degenerating neurons in the hippocampus of the mouse brain following controlled cortical impact (CCI) and found that the majority of degenerating neurons observed were in the dentate gyrus after moderate (0.5 mm cortical deformation) CCI‐TBI. In contrast, there were only a few degenerating neurons observed in the hilus, and we did not observe any degenerating neurons in the CA3 or CA1 regions. Among those degenerating cells in the dentate gyrus, about 80% of them were found in the inner granular neuron layer. Analysis with cell type‐specific markers showed that most of the degenerating neurons in the inner granular neuron layer are newborn immature neurons. Further quantitative analysis shows that the number of newborn immature neurons in the dentate gyrus is dramatically decreased in the ipsilateral hemisphere compared with the contralateral side. Collectively, our data demonstrate the selective death of newborn immature neurons in the hippocampal dentate gyrus following moderate injury with CCI in mice. This selective vulnerability of newborn immature dentate neurons may contribute to the persistent impairment of learning and memory post‐TBI and provide an innovative target for neuroprotective treatment strategies.