Prognostic Value of Different Computed Tomography Scoring Systems in Patients With Severe Traumatic Brain Injury Undergoing Decompressive Craniectomy.

OBJECTIVE: In this study, we investigate the preoperative and postoperative computed tomography (CT) scores in severe traumatic brain injury (TBI) patients undergoing decompressive craniectomy (DC) and compare their predictive accuracy. METHODS: Univariate and multivariate logistic regression analyses were used to determine the relationship between CT score (preoperative and postoperative) and mortality at 30 days after injury. The discriminatory power of preoperative and postoperative CT score was assessed by the area under the receiver operating characteristic curve (AUC). RESULTS: Multivariate logistic regression analysis adjusted for the established predictors of TBI outcomes showed that preoperative Rotterdam CT score (odds ratio [OR], 3.60; 95% confidence interval [CI], 1.13-11.50; P = 0.030), postoperative Rotterdam CT score (OR, 4.17; 95% CI, 1.63-10.66; P = 0.003), preoperative Stockholm CT score (OR, 3.41; 95% CI, 1.42-8.18; P = 0.006), postoperative Stockholm CT score (OR, 4.50; 95% CI, 1.60-12.64; P = 0.004), preoperative Helsinki CT score (OR, 1.44; 95% CI, 1.03-2.02; P = 0.031), and postoperative Helsinki CT score (OR, 2.55; 95% CI, 1.32-4.95; P = 0.005) were significantly associated with mortality. The performance of the postoperative Rotterdam CT score was superior to the preoperative Rotterdam CT score (AUC, 0.82-0.97 vs 0.71-0.91). The postoperative Stockholm CT score was superior to the preoperative Stockholm CT score (AUC, 0.76-0.94 vs 0.72-0.92). The postoperative Helsinki CT score was superior to the preoperative Helsinki CT score (AUC, 0.88-0.99 vs 0.65-0.87). CONCLUSIONS: In conclusion, assessing the CT score before and after DC may be more precise and efficient for predicting early mortality in severe TBI patients who undergo DC.

Default mode network overshadow executive control network in coma emergence and awakening prediction of patients with sTBI.

OBJECTIVE: We aimed to explore the pathogenesis of traumatic coma related to functional connectivity (FC) within the default mode network (DMN), within the executive control network (ECN) and between the DMN and ECN and to investigate its capacity for predicting awakening. METHODS: We carried out resting-state functional magnetic resonance imaging (fMRI) examinations on 28 traumatic coma patients and 28 age-matched healthy controls. DMN and ECN nodes were split into regions of interest (ROIs), and node-to-node FC analysis was conducted on individual participants. To identify coma pathogenesis, we compared the pairwise FC differences between coma patients and healthy controls. Meanwhile, we divided the traumatic coma patients into different subgroups based on their clinical outcome scores at 6 months postinjury. Considering the awakening prediction, we calculated the area under the curve (AUC) to evaluate the predictive ability of changed FC pairs. RESULTS: We found a massive pairwise FC alteration in the patients with traumatic coma compared to the healthy controls [45% (33/74) pairwise FC located in the DMN, 27% (20/74) pairwise FC located in the ECN, and 28% (21/74) pairwise FC located between the DMN and ECN]. Moreover, in the awake and coma groups, there were 67% (12/18) pairwise FC alterations located in the DMN and 33% (6/18) pairwise FC alterations located between the DMN and ECN. We also indicated that pairwise FC that showed a predictive value of 6-month awakening was mainly located in the DMN rather than in the ECN. Specifically, decreased FC between the right superior frontal gyrus and right parahippocampal gyrus (in the DMN) showed the highest predictive ability (AUC = 0.827). CONCLUSION: In the acute phase of severe traumatic brain injury (sTBI), the DMN plays a more prominent role than the ECN and the DMN-ECN interaction in the emergence of traumatic coma and the prediction of 6-month awakening.

Intravitreal injection of Huperzine A promotes retinal ganglion cells survival and axonal regeneration after optic nerve crush.

Traumatic optic neuropathy (TON) is a condition that causes massive loss of retinal ganglion cells (RGCs) and their axonal fibers, leading to visual insufficiency. Several intrinsic and external factors can limit the regenerative ability of RGC after TON, subsequently resulting in RGC death. Hence, it is important to investigate a potential drug that can protect RGC after TON and enhance its regenerative capacity. Herein, we investigated whether Huperzine A (HupA), extracted from a Chinese herb, has neuroprotective effects and may enhance neuronal regeneration following the optic nerve crush (ONC) model. We compared the three modes of drug delivery and found that intravitreal injection of HupA could promote RGC survival and axonal regeneration after ONC. Mechanistically, HupA exerted its neuroprotective and axonal regenerative effects through the mTOR pathway; these effects could be blocked by rapamycin. To sum up, our findings suggest a promising application of HupA in the clinical treatment of traumatic optic nerve.

Knockdown of Porf-2 restores visual function after optic nerve crush injury.

Retinal ganglion cells (RGCs), the sole output neurons in the eyes, are vulnerable to diverse insults in many pathological conditions, which can lead to permanent vision dysfunction. However, the molecular and cellular mechanisms that contribute to protecting RGCs and their axons from injuries are not completely known. Here, we identify that Porf-2, a member of the Rho GTPase activating protein gene group, is upregulated in RGCs after optic nerve crush. Knockdown of Porf-2 protects RGCs from apoptosis and promotes long-distance optic nerve regeneration after crush injury in both young and aged mice in vivo. In vitro, we find that inhibition of Porf-2 induces axon growth and growth cone formation in retinal explants. Inhibition of Porf-2 provides long-term and post-injury protection to RGCs and eventually promotes the recovery of visual function after crush injury in mice. These findings reveal a neuroprotective impact of the inhibition of Porf-2 on RGC survival and axon regeneration after optic nerve injury, providing a potential therapeutic strategy for vision restoration in patients with traumatic optic neuropathy.

Maf1 regulates axonal regeneration of retinal ganglion cells after injury.

Retinal ganglion cells (RGCs) are the sole output neurons that carry visual information from the eye to the brain. Due to various retinal and optic nerve diseases, RGC somas and axons are vulnerable to damage and lose their regenerative capacity. A basic question is whether the manipulation of a key regulator of RGC survival can protect RGCs from retinal and optic nerve diseases. Here, we found that Maf1, a general transcriptional regulator, was upregulated in RGCs from embryonic stage to adulthood. We determined that the knockdown of Maf1 promoted the survival of RGCs and their axon regeneration through altering the activity of the PTEN/mTOR pathway, which could be blocked by rapamycin. We further observed that the inhibition of Maf1 prevented the retinal ganglion cell complex from thinning after optic nerve crush. These findings reveal a neuroprotective effect of knocking down Maf1 on RGC survival after injury and provide a potential therapeutic strategy for traumatic optic neuropathy.

Transcriptome Analyses Reveal Systematic Molecular Pathology After Optic Nerve Crush.

The function of glial cells in axonal regeneration after injury has been the subject of controversy in recent years. Thus, deeper insight into glial cells is urgently needed. Many studies on glial cells have elucidated the mechanisms of a certain gene or cell type in axon regeneration. However, studies that manipulate a single variable may overlook other changes. Here, we performed a series of comprehensive transcriptome analyses of the optic nerve head over a period of 90 days after optic nerve crush (ONC), showing systematic molecular changes in the optic nerve head (ONH). Furthermore, using weighted gene coexpression network analysis (WGCNA), we established gene module programs corresponding to various pathological events at different times post-ONC and found hub genes that may be potential therapeutic targets. In addition, we analyzed the changes in different glial cells based on their subtype markers. We revealed that the transition trend of different glial cells depended on the time course, which provides clues for modulating glial function in further research.