Postoperative delirium (POD) is common in the elderly and is associated with poor clinical outcomes. Reactive oxygen species (ROS) and blood-brain barrier (BBB) damage have been implicated in the development of POD, but the association between these two factors and the potential mechanism is not clear. Cyclophilin A (CypA) is a specifically chemotactic leukocyte factor that can be secreted in response to ROS, which activates matrix metalloproteinase 9 (MMP9) and mediates BBB breakdown. We, therefore, hypothesized that ROS may contribute to anesthesia/surgery-induced BBB damage and delirium-like behavior via the CypA/MMP9 pathway. To test these hypotheses, 16-month-old mice were subjected to laparotomy under 3% sevoflurane anesthesia (anesthesia/surgery) for 3 h. ROS scavenger (N-acetyl-cysteine) and CypA inhibitor (Cyclosporin A) were used 0.5 h before anesthesia/surgery. A battery of behavior tests (buried food test, open field test, and Y maze test) was employed to evaluate behavioral changes at 24 h before and after surgery in the mice. Levels of tight junction proteins, CypA, MMP9, postsynaptic density protein (PSD)-95, and synaptophysin in the prefrontal cortex were assessed by western blotting. The amounts of ROS and IgG in the cortex of mice were observed by fluorescent staining. The concentration of S100β in the serum was detected by ELISA. ROS scavenger prevented the reduction in TJ proteins and restored the permeability of BBB as well as reduced the levels of CypA/MMP9, and further alleviated delirium-like behavior induced by anesthesia/surgery. Furthermore, the CypA inhibitor abolished the increased levels of CypA/MMP, which reversed BBB damage and ameliorated delirium-like behavior caused by ROS accumulation. Our findings demonstrated that ROS may participate in regulating BBB permeability in aged mice with POD via the CypA/MMP9 pathway, suggesting that CypA may be a potential molecular target for preventing POD.

BACKGROUND: Laparoscopic-assisted colorectal surgery is an effective surgery to treat colorectal cancer. During the laparoscopic-assisted colorectal surgery, a midline incision and several trocar insertions are required during the surgery. OBJECTIVE: To observe whether the rectus sheath block based on the locations of the surgical incision and trocars can significantly reduce the pain score on the first day after surgery. DESIGN: This study was a prospective, double-blinded, randomized controlled trial approved by the Ethics Committee of First Affiliated Hospital of Anhui Medical University (registration number: ChiCTR2100044684). SETTINGS: All patients were recruited from 1 hospital. PATIENTS: Forty-six patients aged 18 to 75 years undergoing elective laparoscopic-assisted colorectal surgery were successfully recruited, and 44 patients completed the trial. INTERVENTIONS: Patients in the experimental group received rectus sheath block, with 0.4% ropivacaine 40 to 50 mL, whereas the control group received an equal volume of normal saline. MAIN OUTCOME MEASURES: The primary outcome was pain score on postoperative day 1. Secondary outcomes included patient-controlled analgesia use at 24 and 48 hours after surgery and pain score at 6, 12, and 48 hours after surgery. RESULTS: Pain scores at rest and during activity at 6, 12, 24, and 48 hours after surgery and patient-controlled analgesia consumption of patients on the first day after surgery were significantly lower in the experimental group than those in the control group (all p < 0.05). LIMITATIONS: We did not separate pain into visceral and somatic pain because patients often had difficulty differentiating the source of pain. CONCLUSIONS: Our research indicates that in the context of multimodal analgesia, the rectus sheath block according to the midline incision and the positions of the trocars can reduce the pain scores and consumption of analgesic drugs on the first day after surgery for patients undergoing laparoscopic-assisted colorectal surgery. LA EFICIENCIA DEL BLOQUEO DE LA VAINA DEL RECTO DE VARIOS PUNTOS SEGÚN LA UBICACIÓN DE LA INCISIÓN EN LA CIRUGÍA COLORRECTAL ASISTIDA POR LAPAROSCOPIA: UN ENSAYO CLÍNICO ALEATORIZADO ANTECEDENTES: La cirugía colorrectal asistida por laparoscopia es una cirugía eficaz para tratar el cáncer colorrectal. Durante la cirugía colorrectal asistida por laparoscopia, se requiere una incisión en la línea media y varias inserciones de trócares OBJETIVO: El propósito de nuestro estudio fue observar si el bloqueo de la vaina del recto basado en las ubicaciones de la incisión quirúrgica y los trocares puede reducir significativamente la puntuación del dolor en el primer día después de la cirugía. DISEÑO: Este estudio fue un ensayo controlado aleatorio prospectivo, doble ciego, aprobado por el Comité de Ética del Primer Hospital Afiliado de la Universidad Médica de Anhui (número de registro: ChiCTR2100044684). ESCENARIO: Todos los pacientes fueron reclutados en un hospital. PACIENTES: Cuarenta y seis pacientes de 18 a 75 años de edad que se sometieron a cirugía colorrectal electiva asistida por laparoscopía fueron reclutados con éxito y cuarenta y cuatro pacientes completaron el ensayo. INTERVENCIONES: Los pacientes del grupo experimental recibieron bloqueo de la vaina del recto con 40-50 ml de ropivacaína al 0.4%, mientras que el grupo de control recibió el mismo volumen de solución salina normal. PRINCIPALES MEDIDAS DE RESULTADO: El resultado primario fue la puntuación del dolor en el día 1 postoperatorio. Los resultados secundarios incluyeron el uso de analgesia controlada por el paciente a las 24 y 48 horas después de la cirugía y la puntuación del dolor a las 6, 12, y 48 horas después de la cirugía. RESULTADOS: Las puntuaciones de dolor en reposo y durante la actividad a las 6, 12, 24, y 48 horas después de la cirugía, y el consumo de PCA de los pacientes el primer día después de la cirugía fueron significativamente más bajos en el grupo experimental que en el grupo control (todos p < 0.05). LIMITACIONES: No separamos el dolor en dolor visceral y somático porque los pacientes a menudo tenían dificultades para diferenciar la fuente del dolor. CONCLUSIONES: Nuestra investigación indica que, en el contexto de la analgesia multimodal, el bloqueo de la vaina del recto de acuerdo con la incisión de la línea media y las posiciones de los trócares pueden reducir los puntajes de dolor y el consumo de analgésicos en el primer día después de la cirugía para pacientes sometidos a cirugía colorrectal laparoscópica. (Traducción—Dr. Jorge Silva Velazco)