PSD-95 in the anterior cingulate cortex contributes to neuropathic pain by interdependent activation with NR2B.

Studies suggest that the scaffolding protein, postsynaptic density protein-95 (PSD-95), is involved in multiple neurological dysfunctions. However, the role of PSD-95 in the anterior cingulate cortex (ACC) in neuropathic pain (NP) has not been investigated. The current study addressed the role of PSD-95 in the ACC in NP and its modulating profile with NMDA receptor subunit 2B (NR2B). The NP model was established by chronic constriction injury (CCI) of the sciatic nerve, and mechanical and thermal tests were used to evaluate behavioral hyperalgesia. Protein expression and distribution were evaluated using immunohistochemistry and western blotting. The results showed that PSD-95 and NR2B were co-localized in neurons in the ACC. After CCI, both PSD-95 and NR2B were upregulated in the ACC. Inhibiting NR2B with Ro 25-6981 attenuated pain hypersensitivity and decreased the over-expression of PSD-95 induced by CCI. Furthermore, intra-ACC administration of PSD-95 antisense oligonucleotide not only attenuated pain hypersensitivity but also downregulated the NR2B level and the phosphorylation of cyclic AMP response element-binding protein. These results demonstrated that PSD-95 in the ACC contributes to NP by interdependent activation of NR2B.

Circulation collapse caused by intracardiac thrombosis associated with tranexamic acid administration: A case report.

RATIONALE: Perioperative administration of tranexamic acid has been suggested to reduce bleeding and blood transfusion requirements in patients undergoing orthopedic surgery. Despite being sporadic, the potential risk for thrombotic complications cannot be ignored. However, intracardiac thrombosis associated with tranexamic acid administration is rare. We described a case of circulatory collapse caused by intracardiac thrombosis associated with tranexamic acid administration for a scheduled knee arthroplasty. PATIENT CONCERNS: A 62-year-old male patient was scheduled for a right knee arthroplasty. He had a history of hypertension and had undergone surgery for treatment of right femur fracture 30 years previously. Other than a high platelet count (498 × 109/L), results of laboratory investigations were within normal limits. The ultrasonic examination of both lower limbs showed no thrombosis. Upon sterilizing the surgical area, tranexamic acid (1.6 g) was intravenously administered after induction of anesthesia and intubation. Then the patient had a sudden circulatory collapse. Through cardiopulmonary resuscitation, the patient recovered spontaneous circulation. Transesophageal echocardiography revealed extensive thrombosis in the right atrium and ventricle. DIAGNOSIS: Circulation collapse caused by intracardiac thrombosis. INTERVENTIONS: Thrombolytic therapy was recommended after urgent multidisciplinary consultation. Thus, urokinase was administered intravenously. Fifty minutes after thrombolysis, the mass in ventricle disappeared. A shrunken mass was observed in the right atrium. After another half an hour, no abnormal echoes were seen in the right heart chambers. OUTCOMES: The patient was discharged after 43 days without any organ dysfunction. LESSONS: This case reminds clinicians that perioperative tranexamic acid administration may increase the risk of thrombosis, which needs focused attention from anesthesiologists. Prompt transesophageal echocardiography examination should be done to allow immediate diagnosis and effective thrombolysis therapy when unexplained cardiac arrest occurs during anesthesia.