Overexpressed ski efficiently promotes neurorestoration, increases neuronal regeneration, and reduces astrogliosis after traumatic brain injury.

Traumatic brain injury (TBI) survivors suffer from long-term disability and neuropsychiatric sequelae due to irreparable brain tissue destruction. However, there are still few efficient therapies to promote neurorestoration in damaged brain tissue. This study aimed to investigate whether the pro-oncogenic gene ski can promote neurorestoration after TBI. We established a ski-overexpressing experimental TBI mouse model using adenovirus-mediated overexpression through immediate injection after injury. Hematoxylin-eosin staining, MRI-based 3D lesion volume reconstruction, neurobehavioral tests, and analyses of neuronal regeneration and astrogliosis were used to assess neurorestorative efficiency. The effects of ski overexpression on the proliferation of cultured immature neurons and astrocytes were evaluated using imaging flow cytometry. The Ski protein level increased in the perilesional region at 3 days post injury. ski overexpression further elevated Ski protein levels up to 14 days post injury. Lesion volume was attenuated by approximately 36-55% after ski overexpression, with better neurobehavioral recovery, more newborn immature and mature neurons, and less astrogliosis in the perilesional region. Imaging flow cytometry results showed that ski overexpression elevated the proliferation rate of immature neurons and reduced the proliferation rate of astrocytes. These results show that ski can be considered a novel neurorestoration-related gene that effectively promotes neurorestoration, facilitates neuronal regeneration, and reduces astrogliosis after TBI.

Ideal entry point and trajectory for C2 pedicle screw placement in children: a 3D computed tomography study.

PURPOSE: To identify the ideal entry point for pediatric C2 pedicle screw and to obtain parameters of it for the indication of pediatric atlantoaxial fusion arthrodesis. METHODS: The pediatric cervical CT images were reconstructed into the 3D digital models and the C2 vertebrae were separated. The location of ideal entry point and screw placement related linear and angular parameters were assessed on the 3D digital models. RESULTS: A total of 214 pedicles from 107 C2 digital models were analyzed. The average entry point for C2 was 3.80 ± 2.78 mm medial to the lateral notch (LN) and 2.57 ± 1.70 mm superior to the LN. The average pedicle diameter (PD) was 6.02 ± 1.31 mm, and the average pedicle screw length (PSL) was 25.63 ± 3.46 mm. Statistical differences were found between different sex for PD and PSL (P < 0.05). As patient age increases, using the most lateral and inferior edge of the lateral mass as a reference marker, the entry point tends to move medial and cephalad, when using the LN as a reference marker, the entry point tends to move medial and slightly caudad. Univariate linear regression analysis suggested that these linear parameters were associated with age (P < 0.01). CONCLUSION: In this study, we found that the measurement results of C2 pedicle screw varied based on sex, laterality, and ages for children younger than 18 years. The entry point of the screws facilitating ideal trajectory tends to change in a linear way as a function of age. This information helps the surgeon to establish the specific anatomy related to C2 pedicle screw placement to facilitate fixation in the pediatric patients.

PKC Mediates LPS-Induced IL-1ß Expression and Participates in the Pro-inflammatory Effect of A2AR Under High Glutamate Concentrations in Mouse Microglia.

Pathogens such as bacterial lipopolysaccharide (LPS) play an important role in promoting the production of the inflammatory cytokines interleukin-1 beta (IL-1ß) and tumour necrosis factor-α (TNF-α) in response to infection or damage in microglia. However, whether different signalling pathways regulate these two inflammatory factors remains unclear. The protein kinase C (PKC) family is involved in the regulation of inflammation, and our previous research showed that the activation of the PKC pathway played a key role in the LPS-induced transformation of the adenosine A2A receptor (A2AR) from anti-inflammatory activity to pro-inflammatory activity under high glutamate concentrations. Therefore, in the current study, we investigated the role of PKC in the LPS-induced production of these inflammatory cytokines in mouse primary microglia. GF109203X, a specific PKC inhibitor, inhibited the LPS-induced expression of IL-1ß messenger ribonucleic acid and intracellular protein in a dose-dependent manner. Moreover, 5 µM GF109203X prevented LPS-induced IL-1ß expression but did not significantly affect LPS-induced TNF-α expression. PKC promoted IL-1ß expression by regulating the activity of NF-κB but did not significantly impact the activity of ERK1/2. A2AR activation by CGS21680, an A2AR agonist, facilitated LPS-induced IL-1ß expression through the PKC pathway at high glutamate concentrations but did not significantly affect LPS-induced TNF-α expression. Taken together, these results suggest a new direction for specific intervention with LPS-induced inflammatory factors in response to specific signalling pathways and provide a mechanism for A2AR targeting, especially after brain injury, to influence inflammation by interfering with A2AR.

Reliability and Validity of A Novel Device for Evaluating the Cervical Proprioception.

INTRODUCTION: In clinical practice, cervical proprioception is usually evaluated by calculating the cervical joint position error (JPE) with laser pointer devices (LPD) or cervical range-of-motion (CROM) instruments. As technology continues to improve, more and more advanced tools are used to evaluate cervical proprioception. The purpose of this study was to analyze the reliability and validity of the WitMotion sensor (WS) device in evaluating cervical proprioception, and to explore a cheaper, more convenient, and more practical testing tool. METHODS: Twenty-eight healthy participants (16 women, 12 men; age 25-66 years) were recruited and evaluated for cervical joint position error with a WS and LPD by two independent observers. All participants repositioned their head to the target position and the deviation of repositioning was calculated using these two instruments. The intra- and inter-rater reliability of the instrument were determined by calculating the intraclass correlation coefficients (ICC), and the validity was analyzed by calculating the ICC and the Spearman's correlation. RESULTS: The intra-rater reliability of the WS (ICCs = 0.682-0.774) was higher than that of the LPD (ICCs = 0.512-0.719) for measuring JPE of cervical flexion, right lateral flexion, and left rotation. However, the LPD (ICCs = 0.767-0.796) outperformed the WS (ICCs = 0.507-0.661) in cervical extension, left lateral flexion, and right rotation. For the inter-rater reliability, the ICC values obtained by the WS and the LPD were above 0.70 for all cervical movements except cervical extension and left lateral flexion (ICCs = 0.580-0.679). For the validity, the ICC values were moderate to good (ICCs > 0.614) for measuring JPE in all movements with the WS and the LPD. CONCLUSIONS: Based on the high ICC values of reliability and validity, the novel device can be an alternative tool to evaluate cervical proprioception in clinical practice. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (ChiCTR2100047228).