BACKGROUND: Hematoma clearance has been a proposed therapeutic strategy for hemorrhagic stroke. This study investigated the impact of CX3CR1 (CX3C chemokine receptor 1) activation mediated by r-FKN (recombinant fractalkine) on hematoma resolution, neuroinflammation, and the underlying mechanisms involving AMPK (AMP-activated protein kinase)/PPARγ (peroxisome proliferator-activated receptor gamma) pathway after experimental germinal matrix hemorrhage (GMH). METHODS: A total of 313 postnatal day 7 Sprague Dawley rat pups were used. GMH was induced using bacterial collagenase by a stereotactically guided infusion. r-FKN was administered intranasally at 1, 25, and 49 hours after GMH for short-term neurological evaluation. Long-term neurobehavioral tests (water maze, rotarod, and foot-fault test) were performed 24 to 28 days after GMH with the treatment of r-FKN once daily for 7 days. To elucidate the underlying mechanism, CX3CR1 CRISPR, or selective CX3CR1 inhibitor AZD8797, was administered intracerebroventricularly 24 hours preinduction of GMH. Selective inhibition of AMPK/PPARγ signaling in microglia via intracerebroventricularly delivery of liposome-encapsulated specific AMPK (Lipo-Dorsomorphin), PPARγ (Lipo-GW9662) inhibitor. Western blot, Immunofluorescence staining, Nissl staining, Hemoglobin assay, and ELISA assay were performed. RESULTS: The brain expression of FKN and CX3CR1 were elevated after GMH. FKN was expressed on both neurons and microglia, whereas CX3CR1 was mainly expressed on microglia after GMH. Intranasal administration of r-FKN improved the short- and long-term neurobehavioral deficits and promoted M2 microglia polarization, thereby attenuating neuroinflammation and enhancing hematoma clearance, which was accompanied by an increased ratio of p-AMPK (phosphorylation of AMPK)/AMPK, Nrf2 (nuclear factor erythroid 2–related factor 2), PPARγ, CD36 (cluster of differentiation 36), CD163 (hemoglobin scavenger receptor), CD206 (the mannose receptor), and IL (interleukin)-10 expression, and decreased CD68 (cluster of differentiation 68), IL-1β, and TNF (tumor necrosis factor) α expression. The administration of CX3CR1 CRISPR or CX3CR1 inhibitor (AZD8797) abolished the protective effect of FKN. Furthermore, selective inhibition of microglial AMPK/PPARγ signaling abrogated the anti-inflammation effects of r-FKN after GMH. CONCLUSIONS: CX3CR1 activation by r-FKN promoted hematoma resolution, attenuated neuroinflammation, and neurological deficits partially through the AMPK/PPARγ signaling pathway, which promoted M1/M2 microglial polarization. Activating CX3CR1 by r-FKN may provide a promising therapeutic approach for treating patients with GMH.

Objective: This study aimed to explore the predictive value of the Injury Severity Score (ISS), Trauma Index (TI) and different types of shock indices (SI) on the early mortality risk of acute trauma patients. Methods: Clinical data of acute trauma patients who met the inclusion and exclusion criteria of this study and were treated in the hospital from January 2020 to December 2020 were retrospectively collected, including gender, age, trauma mechanism, severe injury site, ISS, TI, admission vital signs, different types of shock indices (SI), death within 7 days, length of hospital stay, and Glasgow Outcome Score (GOS). The predictive value of the Injury Severity Score, Trauma Index, and different types of shock indices on the risk of early mortality in patients with acute trauma were compared using relevant statistical methods. Results: A total of 283 acute trauma patients (mean age 54.0 ± 17.9 years, 30.74% female) were included, and 43 (15.19%) of the patients died during 7 days of hospitalization. The admission ISS, TI, SI, MSI, and ASI in the survival group were significantly lower than those in the death group, and the difference was statistically significant (p < 0.05). Meanwhile, different trauma assessment tools included in the study have certain predictive value for early mortality risk of trauma patients. Conclusions: The TI indicates a better capability to predict the risk of early death in patients with acute trauma. As the most sensitive predictor, the SI has the greatest reference value in predicting the risk of early death in patients with traumatic shock.

This study aimed at exploring the application of trauma time axis management in the treatment of severe trauma patients by using the Medicalsystem trauma system. We performed a retrospective cohort study involving patients with severe trauma. Patients who were admitted before the application of the Medicalsystem trauma system were divided into before system group; patients who were admitted after the application of the system were divided into after system group. Comparison was made between the two groups. For normally distributed data, means were reported along with standard deviation, and comparisons were made using the independent samples t test. Categorical data were compared using the Chi-square test. The Mann-Whitney U test was used to compare nonparametric variables. There were 528 patients admitted to the study during the study period. There was no significant statistical difference in the time from the start of trauma team to arrive at the resuscitation room between the two groups. The time from arrival at hospital to endotracheal intubation, to ventilator therapy, to blood transfusion, to completion of CT scan, to completion of closed thoracic drainage, to the start of operation, as well as the length of stay in resuscitation room and hospital were significantly lower after the application of the Medicalsystem trauma system. The mortality was decreased by 8.6% in the after system group compared with that in the before system group, but there was no statistical difference. The Medicalsystem trauma system can optimize diagnosis and treatment process for trauma patients, and accordingly improve the treatment efficiency and shorten the treatment time. Therefore, the Medicalsystem trauma system deserves further popularization and promotion.

We here tested the potential activity and the underlying mechanisms of neuroligin-3 (NLGN3) against ischemia-reperfusion-induced neuronal cell injury. In SH-SY5Y neuronal cells and primary murine cortical neurons, NLGN3 activated Akt-mTOR and Erk signalings, and inhibited oxygen and glucose deprivation (OGD)/re-oxygenation (OGD/R)-induced cytotoxicity. Akt activation was required for NLGN3-induced neuroprotection. Gαi1/3 mediated NLGN3-induced downstream signaling activation. NLGN3-induced Akt-S6K1 activation was largely inhibited by Gαi1/3 silencing or knockout. Significantly, NLGN3-induced neuroprotection against OGD/R was almost abolished by Gαi1/3 silencing or knockout. In vivo, the middle cerebral artery occlusion (MCAO) procedure induced NLGN3 cleavage and secretion, and increased its expression and Akt activation in mouse brain tissues. ADAM10 (A Disintegrin and Metalloproteinase 10) inhibition blocked MCAO-induced NLGN3 cleavage and secretion, exacerbating ischemic brain injury in mice. Neuronal silencing of NLGN3 or Gαi1/3 in mice also inhibited Akt activation and intensified MCAO-induced ischemic brain injury. Conversely, neuronal overexpression of NLGN3 increased Akt activation and alleviated MCAO-induced ischemic brain injury. Together, NLGN3 activates Gαi1/3-Akt signaling to protect neuronal cells from ischemia-reperfusion injury.

Background. Enteral nutrition (EN) is often used in patients with traumatic brain injury (TBI), but some studies have shown that EN has its disadvantages. However, it is not clear which nutritional support is appropriate to reduce mortality, improve prognosis, and improve nutritional status in patients with TBI. We performed this Bayesian network meta-analysis to evaluate the improvement of nutritional indicators and the clinical outcomes of patients with TBI. Methods. We systematically searched PubMed, Embase, Cochrane Library, and Web of Science from inception until December 2021. All randomized controlled trials (RCTs) which compared the effects of different nutritional supports on clinical outcomes and nutritional indicators in patients with TBI were included. The co-primary outcomes included mortality and the value of serum albumin. The secondary outcomes were nitrogen balance, the length of study (LOS) in the ICU, and feeding-related complications. The network meta-analysis was performed to adjust for indirect comparison and mixed treatment analysis. Results. 7 studies enroll a total of 456 patients who received different nutritional supports including parenteral nutrition (PN), enteral nutrition (EN), and PN + EN. No effects on in-hospital mortality (Median RR = 1.06, 95% Crl = 0.12 to 1.77) and the value of 0-1 days of serum albumin were found between the included regimens. However, the value of 11–13 days of serum albumin of EN was better than that of PN (WMD = −4.95, 95% CI = −7.18 to −2.72, , I² = 0%), and 16–20 days of serum albumin of EN + PN was better than that of EN (WMD = −7.42, 95% CI = −14.51 to −0.34, , I² = 90%). No effects on the 5–7 day nitrogen balance were found between the included regimens. In addition, the complications including pneumonia and sepsis have no statistical difference between EN and PN. EN was superior to PN in terms of LOS in the ICU and the incidence rate of stress ulcers. Although the difference in indirect comparisons between the included regimens was not statistically significant, the results showed that PN seemed to rank behind other regimens, and the difference between them was extremely small. Conclusion. Available evidence suggests that EN + PN appears to be the most effective strategy for patients with TBI in improving clinical outcomes and nutritional support compared with other nutritional supports. Further trials are required.