The nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome plays a crucial role in the prognosis of subarachnoid hemorrhage (SAH). WNK1 kinase negatively regulates NLRP3 in various inflammatory conditions, but its role in early brain injury (EBI) after SAH remains unclear. In this study, we used an in vivo SAH model in rats/mice and AAV-WNK1 intraventricular injection to investigate its neuroprotective mechanisms. WNK1 expression was significantly reduced in SAH patient blood and SAH model brain tissue, correlating negatively with microglial activation. AAV-WNK1 alleviated brain edema, neuronal necrosis, behavioral deficits, and inflammation by inhibiting NLRP3 inflammasome activation. In hemin-stimulated BV-2 cells, WNK1 overexpression reduced NLRP3 activation and inflammatory cytokines. Chloride counteracted WNK1's inhibitory effects, and WNK1 suppressed P2X7R-induced NLRP3 activation. Mechanistically, WNK1 functioned via the OXSR1/STK39 pathway. These findings highlight WNK1 as a key regulator of intracellular chloride balance and neuroinflammation, presenting a potential therapeutic target for SAH treatment.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Subarachnoid Hemorrhage/complications* ; Inflammasomes/metabolism* ; Rats ; Mice ; Neuroinflammatory Diseases/metabolism* ; WNK Lysine-Deficient Protein Kinase 1/genetics* ; Male ; Humans ; Chlorides/metabolism* ; Mice, Inbred C57BL ; Rats, Sprague-Dawley ; Brain Injuries/metabolism* ; Microglia/metabolism* ; Protein Serine-Threonine Kinases

Objective:To explore the clinical value of the three-dimensional fat suppression fast spoiled gradient echo (3D-FS-FSPGR) MRI sequence in the preoperative evaluation of congenital radial polydactyly.Methods:The data of children with congenital radial polydactyly who underwent surgical treatment in the Department of Orthopedics at Shanxi Children’s Hospital from May 2021 to April 2022 were retrospectively analyzed. Preoperative X-ray examinations and MRI 3D-FS-FSPGR sequence scans were performed on the children. Radiologists first described the morphological characteristics of the articular cartilage, and then orthopedic surgeons performed the Wassel classification based on the X-ray and MRI imaging result, focusing on the bifurcation level, morphology, and articular surface of the phalangeal and metacarpal cartilage. The corresponding surgical method was selected according to the Wassel classification, and intraoperative incision exploration was used as the gold standard. Six months after surgery, the surgical outcome was evaluated using the modified Tada scoring system [with a total score of 0-7, and classified as excellent: >5 points, good: 3-5 points, and poor: <3 points; the excellent and good rate = (excellent + good) cases/total number of cases × 100%]. The appearance, function and recurrence of the operated finger were evaluated 1 year after surgery. Descriptive statistics were performed using SPSS 26.0 software, and the Kappa coefficient was used to evaluate the consistency of the Wassel classification result between radiographs, MRI 3D-FS-FSPGR sequences and intraoperative exploration respectively.Results:A total of 45 children (55 fingers) with congenital radial polydactyly were enrolled, including 25 males and 20 females, aged 5 to 60 months, with the median age of 9 months. Unilateral findings were seen in 35 cases and bilateral findings in 10 cases. MRI 3D-FS-FSPGR imaging sequences clearly demonstrated the level of cartilage bifurcation and bone tissue growth and development, which were consistent with intraoperative exploration findings. The accuracy of the MRI 3D-FS-FSPGR Wassel classification was 100% (55/55), and the accuracy of the X-ray Wassel classification was 81.8% (45/55). Disagreements were found in the classifications of five fingers: three with X-ray classifications of Wassel type Ⅳ but actually classified as type Ⅲ, and two with X-ray classifications of Wassel type Ⅳ but actually classified as type Ⅴ. The Kappa coefficients were all >0.85. All patients were followed up for 1 year. The modified Tada score showed excellent in 41 fingers, good in 6 fingers, and poor in 8 fingers, for an excellent and good rate of 85.5% (47/55). At final follow-up, the reconstructed thumbs showed significant improvement in appearance, with normal bone axis restoration, no deviation of the digits, and normal nail appearance. There was no significant scarring or contracture. Functions of thumb flexion, extension, grasping, and opposition were good. There was no postoperative deformity or recurrence.Conclusion:MRI 3D-FS-FSPGR sequences can accurately classify congenital radial polydactyly preoperatively, optimize the surgical incision and osteotomy alignment, and achieve excellent surgical outcomes.

Objective:To explore the clinical value of the three-dimensional fat suppression fast spoiled gradient echo (3D-FS-FSPGR) MRI sequence in the preoperative evaluation of congenital radial polydactyly.Methods:The data of children with congenital radial polydactyly who underwent surgical treatment in the Department of Orthopedics at Shanxi Children’s Hospital from May 2021 to April 2022 were retrospectively analyzed. Preoperative X-ray examinations and MRI 3D-FS-FSPGR sequence scans were performed on the children. Radiologists first described the morphological characteristics of the articular cartilage, and then orthopedic surgeons performed the Wassel classification based on the X-ray and MRI imaging result, focusing on the bifurcation level, morphology, and articular surface of the phalangeal and metacarpal cartilage. The corresponding surgical method was selected according to the Wassel classification, and intraoperative incision exploration was used as the gold standard. Six months after surgery, the surgical outcome was evaluated using the modified Tada scoring system [with a total score of 0-7, and classified as excellent: >5 points, good: 3-5 points, and poor: <3 points; the excellent and good rate = (excellent + good) cases/total number of cases × 100%]. The appearance, function and recurrence of the operated finger were evaluated 1 year after surgery. Descriptive statistics were performed using SPSS 26.0 software, and the Kappa coefficient was used to evaluate the consistency of the Wassel classification result between radiographs, MRI 3D-FS-FSPGR sequences and intraoperative exploration respectively.Results:A total of 45 children (55 fingers) with congenital radial polydactyly were enrolled, including 25 males and 20 females, aged 5 to 60 months, with the median age of 9 months. Unilateral findings were seen in 35 cases and bilateral findings in 10 cases. MRI 3D-FS-FSPGR imaging sequences clearly demonstrated the level of cartilage bifurcation and bone tissue growth and development, which were consistent with intraoperative exploration findings. The accuracy of the MRI 3D-FS-FSPGR Wassel classification was 100% (55/55), and the accuracy of the X-ray Wassel classification was 81.8% (45/55). Disagreements were found in the classifications of five fingers: three with X-ray classifications of Wassel type Ⅳ but actually classified as type Ⅲ, and two with X-ray classifications of Wassel type Ⅳ but actually classified as type Ⅴ. The Kappa coefficients were all >0.85. All patients were followed up for 1 year. The modified Tada score showed excellent in 41 fingers, good in 6 fingers, and poor in 8 fingers, for an excellent and good rate of 85.5% (47/55). At final follow-up, the reconstructed thumbs showed significant improvement in appearance, with normal bone axis restoration, no deviation of the digits, and normal nail appearance. There was no significant scarring or contracture. Functions of thumb flexion, extension, grasping, and opposition were good. There was no postoperative deformity or recurrence.Conclusion:MRI 3D-FS-FSPGR sequences can accurately classify congenital radial polydactyly preoperatively, optimize the surgical incision and osteotomy alignment, and achieve excellent surgical outcomes.