Functional and structural alterations of clustered postsynaptic ligand gated ion channels in neuronal cells are thought to contribute to synaptic plasticity and memory formation in the human brain. Here, we describe a novel molecular mechanism for structural alterations of NR1 subunits of the NMDA receptor. In cultured rat spinal cord neurons, chronic NMDA receptor stimulation induces disappearance of extracellular epitopes of NMDA receptor NR1 subunits, which was prevented by inhibiting matrix metalloproteinases (MMPs). Immunoblotting revealed the digestion of solubilized NR1 subunits by MMP-3 and identified a fragment of about 60 kDa as MMPs-activity-dependent cleavage product of the NR1 subunit in cultured neurons. The expression of MMP-3 in the spinal cord culture was shown by immunoblotting and immunofluorescence microscopy. Recombinant NR1 glycine binding protein was used to identify MMP-3 cleavage sites within the extracellular S1 and S2-domains. N-terminal sequencing and site-directed mutagenesis revealed S542 and L790 as two putative major MMP-3 cleavage sites of the NR1 subunit. In conclusion, our data indicate that MMPs, and in particular MMP-3, are involved in the activity dependent alteration of NMDA receptor structure at postsynaptic membrane specializations in the CNS.
Purpose The purpose of this study was to determine the outcome of unstable type C pelvic fractures treated with posterior stabilisation and the anterior subcutaneous internal fixator (ASIF). Methods Altogether, 36 consecutive patients were treated for unstable type C pelvic ring fractures using posterior stabilisation and ASIF. After a minimum of 18 months, the clinical and radiological outcome was retrospectively investigated. Results Overall, three patients (8.3 %) died, and 31 patients (86 %) were available for follow-up after a mean of 4.5 years. Thirty of 31 patients (97 %) showed radiographic bone consolidation of both the posterior and anterior pelvic ring. Only one non-union and two infections due to the anterior device were observed. The total German pelvic outcome score showed an excellent or good rating for 64.5 % of the patients, and a fair or poor for 35.5 %. The SF-12 questionnaire showed a significantly reduced total score for physical and mental health compared to a general reference population. Conclusions The ASIF represents an innovative surgical procedure for the treatment of type C pelvic ring fractures. In the medium term, patient satisfaction was high and the complication rate was low, despite the small number of patients. More cases must be investigated before the procedure can be recommended in general, possibly replacing the external fixator for the treatment of pelvic ring fractures in the future.
The pelvic subcutaneous cross-over internal fixator is a minimally invasive technique for the fixation of instable anterior pelvic ring fractures. A USS-II-VAS screw is anchored bilaterally in the supra-acetabular region of the os ileum by a mini-incision approach. An angled fixation rod is inserted subcutaneously and after successful closed reduction attached to the screws forming a locking internal fixation. In a retrospective study of the clinical and radiological outcomes of 19 patients after an average follow-up of 2.54 years, results were excellent and good in 31.6%, moderate in 63.2% and poor in 5.3%. Complications were one wound infection, one loosening of the VAS screw and seven temporary lesions of the lateral femoral cutaneous nerve. The main benefits are a simple surgical technique preventing damage to soft tissue, a low risk of neurovascular lesions and the avoidance of pin infections. Moreover patients with multiple trauma profit from a shorter time of surgery and greater comfort allowing a prone position. The new procedure combines the advantages of internal osteosynthesis and a minimally invasive technique, providing early mobilization under full-weight bearing for instable pelvic fractures.
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