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.

Advanced age and low educational level are associated with decreased BDNF serum levels. Decreased BDNF serum levels correspond to the severity of cognitive impairment. There is no correlation between BDNF serum levels and depressive symptoms.

Injury of peripheral nerve is associated with the development of post-traumatic neuroma at the end of the proximal stump, often being the origin of neuropathic pain. This type of pain is therapy-resistant and therefore extremely nagging for patients. We examined the influence of the microcrystallic chitosan gel applied to the proximal stump of totally transected sciatic nerve on the neuroma formation and neuropathic pain development in rats. In 14 rats, right sciatic nerve was transected and the distal stump was removed to avoid spontaneous rejoining. In the chitosan (experimental) group (n = 7), the proximal stump was covered with a thin layer of the microcrystallic chitosan gel. In control animals (n = 7), the cut nerve was left unsecured. Autotomy, an animal model of neuropathic pain, was monitored daily for 20 weeks following surgery. Then, the animals were perfused transcardially and the proximal stumps of sciatic nerves were dissected and subjected to histologic evaluation. The presence, size, and characteristics of neuromas as well as extraneural fibrosis were examined. In chitosan group, the incidence and the size of the neuroma were markedly reduced, as compared with the control group; however, there was no difference in autotomy behavior between groups. In addition, extraneural fibrosis was significantly reduced in chitosan group when compared to the control group. The results demonstrate beneficial influence of microcrystallic chitosan applied to the site of nerve transection on the development of post-traumatic neuroma and reduction of extraneural fibrosis, however without reduction of neuropathic pain.

BackgroundAccording to recent studies, brain-derived neurotrophic factor (BDNF) probably plays a role in development of cerebral ischemia and can be significant for the prognosis of improved mobility after stroke. The aim of this prospective study was to evaluate the blood concentration of BDNF during the 1st day of first-ever ischemic stroke and find a potential association between BDNF concentration and the neurological status in the acute period, as well as between BDNF and the functional status in the sub-acute phase of stroke.Material/MethodsThe prospective study involved 87 patients aged 39–99 years (42 women, 45 men) with first-in-life complete ischemic stroke.All study subjects underwent analysis as follows: BDNF blood concentration and neurological status according to NIHSS on the 1st day of stroke, comorbidities, etiological type of ischemic stroke by ASCOD, and functional status on the 14th and 90th day after the onset according to mRankin scale.ResultsMean concentration of BDNF in the study group was 9.96 ng/mL±5.21, median 10.39 ng/mL. Patients aged ≤65 years (25 individuals) had a significantly higher mean concentration of BDNF (11.94 ng/mL±4.46; median 12.34 ng/mL) than the older subjects (62 individuals) with a mean concentration of 9.17 ng/mL±5.32 (median 8.66 ng/mL).The mean score by mRankin scale on the 90th day was significantly higher among patients with lower concentrations of BDNF on the 1st day of stroke, which reflects their poorer functional status.The functional status on the 90th day was significantly worse (3–6 points by Rankin scale) in patients who had BDNF below the mean value in the acute phase of stroke.The independent factors for poor functional status of patients on the 90th day after stroke were a score >4 points by NIHSS (RR 1.14; 95% CI: 1.00–1.31; p=0.027) and the concentration of BDNF below the mean value (assessed on the 1st day of stroke) (RR 14.49; CI 4.60–45.45; p=0.000).ConclusionsThe neurological status and concentration of BDNF on the 1st day of ischemic stroke are independent prognostic factors in medium-term observation.Reduction in the concentration of BDNF in the acute phase of stroke is a factor for poor prognosis in terms of the functional status of patients on the 90th day after onset.

Nutritional imbalance underlies many disease processes but can be very beneficial in certain cases; for instance, the antiepileptic action of a high fat and low carbohydrate ketogenic diet. Besides this therapeutic feature it is not clear how this abundant fat supply may affect homeostasis, leading to side effects. A ketogenic diet is used as anti-seizure therapy i.a. in tuberous sclerosis patients, but its impact on concomitant tumor growth is not known. To examine this we have evaluated the growth of renal lesions in Eker rats (Tsc2+/−) subjected to a ketogenic diet for 4, 6 and 8 months. In spite of existing opinions about the anticancer actions of a ketogenic diet, we have shown that this anti-seizure therapy, especially in its long term usage, leads to excessive tumor growth. Prolonged feeding of a ketogenic diet promotes the growth of renal tumors by recruiting ERK1/2 and mTOR which are associated with the accumulation of oleic acid and the overproduction of growth hormone. Simultaneously, we observed that Nrf2, p53 and 8-oxoguanine glycosylase α dependent antitumor mechanisms were launched by the ketogenic diet. However, the pro-cancerous mechanisms finally took the ascendency by boosting tumor growth.

AbstractMatrix metalloproteinase 9 (MMP-9) plays an important role in inflammatory and pathological processes by enabling the inflow of leukocytes to the site of infection or tissue damage. MMP-9 and tissue inhibitor of metalloproteinase 1 (TIMP-1) have been described as potential prognostic biomarkers in various clinical settings. The aim of the study was to evaluate the usefulness of plasma levels of MMP-9 and TIMP-1 as well as the MMP-9/ TIMP-1 ratio in predicting the outcome in patients admitted to the intensive care unit (ICU). The study included 56 critically ill patients with multiple organ failure. Plasma levels of MMP-9 and TIMP-1 were determined on hospitalization day 1, 2, 3 and 7. Nineteen (35.7%) patients died. The level of TIMP-1 was statistically significantly higher on day 1 and 7 of hospitalization in non-survivors, as compared to survivors (p=0.01). A statistically significant positive correlation was found between MMP-9 and TIMP-1. The MMP-9/TIMP-1 ratio was comparable in both groups during of observation (0.62 on day 1). The MMP-9/TIMP-1 ratio was positively correlated with the level of lactate and negatively correlated with platelet count. Likewise, TIMP-1 was positively correlated with the level of lactate. The level of MMP-9 was higher in the non-survivor group only on day 7 of observation. In conclusion, although TIMP-1 and MMP-9 concentrations were higher in non-survivors and the MMP-9/TIMP-1 ratio was related to some parameters of critical illness, further research is needed to verify whether they can serve as reliable biomarkers for early prognostication of ICU patients.

Subarachnoid hemorrhage (SAH) develops when extravasated arterial blood enters subarachnoid space and mixes with cerebrospinal fluid. As a result, many pathologies develop, including arterial vasospasm that leads to the ischemia and hypoxia. Immuno-inflammatory response is considered as the cause of numerous complications following SAH. In the study, we examined the role of one of major cytokines, interleukin 1-beta (IL-1beta), on the vascular pathologies after experimental SAH in adult rats. SAH was produced by injection of 150 uL of autologous arterial blood into cisterna magna. In 50% of animals, IL-1beta activity was inhibited by intracerebroventricular administration of anti-rat IL-1beta antibodies (SAH' groups). Control group consisted of sham-operated rats. Ninety minutes or 24 hrs following surgery, animals were perfused transcardially and whole brains were collected. Spasm index (ratio of vessel diameter to the mean wall thickness) of basilar artery as well as blood vessel density (number of vessels per square millimeter) at brain stem and frontal part of the brain were measured. SAH led to the vasospasm of basilar artery and increased the density of blood vessel. Neutralization of IL-1beta activity significantly reduced both the vasospasm and blood vessel density only 24 hrs after SAH. The results demonstrate an important role of IL-1beta in the delayed development of vascular pathologies after subarachnoid hemorrhage.

PurposeEstradiol (E2)-loaded poly(L-lactide-co-glycolide-trimethylenecarbonate) (P(L-LA:GA:TMC)) rods with shape-memory were developed for the treatment of neurodegenerative diseases. Usefulness of the extrusion method in the obtaining process was also considered. The influence of structural and surface properties during hydrolytic degradation was developed. The possible therapeutic aspect of rods with E2 was determined.MethodsThe extruded rods were incubated in a PBS solution (pH 7.4, 37°C, 240 rpm). The amount of released E2 in vitro conditions was estimated by UV-VIS method. The following methods in the degradation of rods were applied: NMR, DSC, FTIR, GPC, SEM, and optical microscopy. Changes in water uptake and weight loss were also determined. In vivo study was performed on rats. Measurements of E2 level were performed before and after ovariectomy of rats using ELISA method. A sample of tissue adjacent to the site of the rod implantation was analysed under an optical microscope.ResultsA stable and steady degradation process ensured zero-order release of E2. The in vivo study indicated a significant increase in the E2 level in serum after ovariectomy. Moreover, structural and surface features indicated that the extrusion method was appropriate for obtaining E2-loaded rods.ConclusionsShape-memory P(L-LA:GA:TMC) rods with E2 are an adequate proposal for further research in the field of neurological disorders.