ABSTRACT
Following peripheral nerve injury, a sequence of events termed Wallerian degeneration (WD) takes place at the distal stump in order to allow the regenerating axons to grow back toward the target organs. Schwann cells (SCs) play a lead role in this by initiating the inflammatory response attracting macrophages and immune cells, as well as producing neurotrophic signals that are essential for nerve regeneration. The majority of existing research has focused on tools to improve regeneration, overlooking the critical degeneration phase. This is also due to the lack of in vitro models recapitulating the features of in vivo WD. In particular, to understand the initial SC response following injury, and to investigate potential interventions, a model that isolates the nerve from other systemic influences is required. Stem cell intervention has been extensively studied as a potential therapeutic intervention to augment regeneration; however, data regarding their role in WD is lacking. Thus, in this study we describe an in vitro model using rat sciatic nerve explants degenerating up to 14 days. Characterisation of this model was performed by gene and protein expression for key markers of WD, in addition to immunohistochemical analysis and electron microscopy. We found changes in keeping with WD in vivo: upregulation of repair program protein CJUN, downregulation of myelin protein genes and subsequent disorganisation and breakdown of myelin structure. As a means of testing the effects of stem cell intervention on WD we established indirect co-cultures of human adipose-derived mesenchymal stem cells (AD-MSC) with the degenerating nerve explants. The stem cell intervention potentiated neurotrophic factors and Cjun expression. We conclude that our in vitro model shares the main features of in vivo WD, and we provide proof of principle on its effectiveness to study experimental approaches for nerve regeneration focused on the events happening during WD.
ABSTRACT
BACKGROUND: Idiopathic intracranial hypertension (IIH) denotes the condition of increased intracranial pressure without a clear underlying pathologic condition of the brain. The treatment plan should be conducted to save vision. Treatment options include medications, serial lumbar punctures, and surgical intervention. Surgery is indicated once visual loss continues despite optimum medical therapy. METHODS: This is a prospective study carried out during a period of 2 years. Cases were those who fulfilled the modified Dandy criteria for the diagnosis of IIH. All cases experienced a previously failed lumboperitoneal shunt. This study was approved by The Ethical Committee of Mansoura Faculty of Medicine. The following data were gathered for analysis: age, sex, presenting symptoms, number of shunt failures, apparent causes of failure, cerebrospinal fluid opening pressure on lumbar puncture, visual acuity before surgery, operative time, visual acuity at 3 and 6 months and 1 year, and any procedure-related or device-related complication. RESULTS: Our study included 12 patients with lumboperitoneal shunt failure, all of which were women with mean age of 33 years. The major presenting symptom was headache. The main cause of failure was shunt migration (n = 10, 83.3%). Mean cerebrospinal fluid opening pressures was 37 cmH2O. The mean operative time was 42.5 minutes. CONCLUSIONS: The lumbopleural shunt is a potentially effective technique in terms of symptoms control and vision improvement in treatment of IIH. The technique is safe, less time-consuming, and more suitable for morbid obese patients with high body fat percentages.
