Fig. 7: Changes in the locus coeruleus are a feature of the brainstem response to mild traumatic brain injury. | Nature Communications

Fig. 7: Changes in the locus coeruleus are a feature of the brainstem response to mild traumatic brain injury.

From: Single-nucleus and spatial signatures of the brainstem in normal brain and mild traumatic brain injury in male mice

Fig. 7

a The function of the brainstem, especially the locus coeruleus, was evaluated using a tail-flick test, in which prolonged delay time represents poor locus coeruleus function. Typically, the delay time was 12.56 ± 8.60 s. At 1 h post-injury, the delay time increased to more than 30 s, indicating poor locus coeruleus function; however, after 24 h, the delay time decreased to 25.03 ± 6.00 s, indicating slight functional recovery. (Data are presented as mean values ± SEM and using one-way ANOVA; ***P = 0.0002; control vs. injury-1 h; n.s.; injury-1 h vs. injury-24 h;**P = 0.005; control vs. injury-24h; n = 10 in the control group, n = 6 in the injury-1 h group, n = 6 in the injury-24 h group) Source data are provided as a Source Data file. b We present the score of neuronal activity at the spatial level. Typically, neuronal activity is robust across all brain regions (upper). After the injury, neurons in most regions exhibit low activity; however, neuronal activity in the locus coeruleus (LC) and the intermediate reticular nucleus (IRt) is increased. c The SCENIC package was used to predict transcription factor (TF) activity after traumatic brain injury, and we found that the activity of 33 TFs increased at 24 h post-injury. d We retrieved the genes targeted by the most activated TFs and conducted GSEA enrichment analysis performed by permutation test and FDR adjust; the genes are related to neuropeptide signalling, the molecular transducer activity process, and noradrenaline-related blood pressure functions. e Pseudo-time analysis was performed to investigate the injury-induced changes in the number of noradrenergic neurons that are clustered in the LC and revealed that during post-injury, Dbh and Net were gradually up-regulated. Therefore, an injury-induced noradrenergic neuronal response was observed. f Pseudo-time-related genes that were highly expressed after injury were identified, and enrichment analysis was performed. GO analysis, conducted using the hypergeometric test and BH multiple hypothesis correction, revealed that these genes are involved in neurotransmitter release and binding.

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