In the central nervous system, tuberous sclerosis complex (TSC) is characterized by a range of lesions including cortical tubers, white matter heterotopias, subependymal nodules, and subependymal giant cell astrocytomas (SEGAs). Recent studies have implicated an important role for the TSC genes TSC1 and TSC2, in a signaling pathway involving the mammalian target of rapamycin (mTOR) kinase. We performed immunohistochemical and genetic analyses on SEGAs from 7 TSC patients, 4 with mutations in TSC1, and 3 with mutations in TSC2. SEGA cells show high levels of phospho-S6K, phospho-S6, and phospho-Stat3, all proteins downstream of and indicative of mTOR activation. Such expression is not seen in histologically normal control tissue. Five of 6 SEGAs also showed evidence of biallelic mutation of TSC1 or TSC2, suggesting that SEGAs develop due to complete loss of a functional tuberin-hamartin complex. We conclude that TSC SEGAs likely arise through a two-hit mechanism of biallelic inactivation of TSC1 or TSC2, leading to activation of the mTOR kinase.

Acute cerebral ischemia triggers local and systemic immune response. The aims of this project was to assess the blood serum concentration of the markers of inflammation and markers of the blood brain barrier damage on the first day of ischemic stroke, and the mutual correlations between these marker levels. Methods Our prospective study included 138 patients with first-in-life stroke, who were analyzed according to: plasma concentration of the following markers on the first day of stroke: Il-2 and IL-6, S100B, TNF alfa, GRN, NSE, uPA, VEGF, BDNF, CRP, leucocyte and thrombocyte counts; their neurological status on the first day of stroke (NIHSS) and their functional status at 30 days following stroke (mRS). Result The study included 138 patients with mean age: 73.11 ± 11.48 [36-103]. Patients with a higher score on the NIHSS than those obtaining lower scores showed significantly higher concentrations of TNF-alpha, WBC, CRP, NSE, IL-6 and S100B. Patients with a higher score on the mRS than those obtaining lower scores showed significantly higher concentrations of WBC, CRP, GRN, IL-6, S100B. Factors with an independent influence on the neurological status on the first day of stroke were: sex, WBC, PLT, CRP, S100B and IL-6 levels. Atrial fibrillation, leukocyte count, CRP, NSA, uPA, interleukin 6 and S100B showed an independent impact on the functional status on the 30th day of stroke. Patients with symptomatic atherosclerosis of carotid/cerebral and/or coronary arteries, as compared to others, were older (p= 0.003) and had higher levels of CRP, Il-6, and S100B. In each case, the differences were statistically significant. Conclusions The concentration of Il-6 and S100B on the first day of stroke are significant for both the neurological status and the functional status in the acute period of the disease. Increased CRP and leukocyte count are associated with a worse prognosis regarding the course of acute stroke. The expression of pro-inflammatory agents and markers of blood-brain barrier damage in the acute phase of stroke is more prominent in patients with symptomatic atherosclerosis than in patients with no clinical features of atherosclerosis.

Painful neuroma is a common sequela of peripheral nerve injury which is usually resistant to pharmacologic treatment and requires surgical intervention. The widely accepted methods of neuroma management prevent regrowth of nerve fibers, thus precluding any functional repair. The present study reviews the currently used methods and experimental approaches to prevent and cure neuromas developing after peripheral nerve injury. The main recommendations are as follows. Special care should be taken to minimize scar formation when operating on peripheral nerves. The laser or scissors transection methods should be used to cut the nerve rather than electrocoagulation or cryoneurolysis. Direct nerve reconstruction, or, if a gap occurs, nerve grafting, should be performed immediately after nerve injury. Surgical resection of recurrent neuroma followed by implantation of the nerve into the muscle or capping the nerve stump with epineural graft seems to be the most effective method of prevention.

Understanding the pathomechanisms behind peripheral nerve damage and learning the course of regeneration seem to be crucial for selecting the appropriate methods of treatment. Autografts are currently the gold standard procedure in nerve reconstruction. However, due to the frequency of complications resulting from autografting and a desire to create a better environment for the regeneration of the damaged nerve, artificial conduits have become an approved alternative treatment method. The aim of this mini-review is to present the nerve scaffolds that have been applied in clinical practice to date, and the potential directions of developments in nerve conduit bioengineering. Articles regarding construction and characterization of nerve conduits were used as the theoretical background. All papers, available in PubMed database since 2000, presenting results of application of artificial nerve conduits in clinical trials were included into this mini-review. Fourteen studies including ≤10 patients and 10 trials conducted on >10 patients were analyzed as well as 24 papers focused on artificial nerve conduits per se. Taking into consideration the experiences of the authors investigating nerve conduits in clinical trials, it is essential to point out the emergence of bioresorbable scaffolds, which in the future may significantly change the treatment of peripheral nerve injuries. Also worth mentioning among the advanced conduits are hybrid conduits, which combine several modifications of a synthetic material to provide the optimal regeneration of a damaged nerve.

Retinal neurons are not able to undergo spontaneous regeneration in response to damage. A variety of stressors, i.e., UV radiation, high temperature, ischemia, allergens, and others, induce reactive oxygen species production, resulting in consecutive alteration of stress-response gene expression and finally can lead to cell apoptosis. Neurons have developed their own endogenous cellular protective systems. Some of them are preventing cell death and others are allowing functional recovery after injury. The high efficiency of these mechanisms is crucial for cell survival. In this review we focus on the contribution of the most recently studied endogenous neuroprotective factors involved in retinal ganglion cell (RGC) survival, among which, neurotrophic factors and their signaling pathways, processes regulating the redox status, and different pathways regulating cell death are the most important. Additionally, we summarize currently ongoing clinical trials for therapies for RGC degeneration and optic neuropathies, including glaucoma. Knowledge of the endogenous cellular protective mechanisms may help in the development of effective therapies and potential novel therapeutic targets in order to achieve progress in the treatment of retinal and optic nerve diseases.