Edyta Olakowska

Interleukin-1β Increases Release of Endothelin-1 and Tumor Necrosis Factor as Well as Reactive Oxygen Species by Peripheral Leukocytes During Experimental Subarachnoid Hemorrhage

In the subarachnoid hemorrhage (SAH) blood mixes with cerebrospinal fluid, what starts immunoinflammatory processes - increased synthesis of proinflammatory cytokines, and formation of reactive oxygen species (ROS), resulting in pre-activation of different populations of peripheral leukocytes. Migration of leukocytes to the brain parenchyma through broken blood brain barrier may produce extra brain tissue injury besides of that resulting from SAH. We examined in adult rats the effect of interleukin-1β (IL-1β) neutralization on secretion of cytokines as well as production of ROS in the course of SAH. SAH was produced by injection of 150 μL of autologous arterial blood into cisterna magna. In 50% of animals, IL-1beta activity was inhibited by intracerebroventricular administration of anti-rat IL-1β antibodies. Ninety minutes or 24 hrs following surgery, blood samples were drawn from the extraorbital plexus and centrifuged to obtain two leukocyte subpopulations - polymorphonuclear (PMN) and mononuclear (MN). The chemiluminescence, a hallmark of ROS synthesis, was measured in PMNs. In supernatants from MNs cultures, concentrations endothelin-1 (ET-1), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were assessed. SAH caused the increase ofn PMNs chemiluminescence as well as the increase of production of ET-1 and TNF-α by MNs but had no influence on IL-6 concentration. Neutralization of IL-1β resulted in significant decrease of chemiluminescence as well as concentration of both ET-1 and TNF-α, while IL-6 concentration was increased. These revealed an important role of IL-1β in the activation of peripheral leukocytes in the course of subarachnoid hemorrhage.

Childhood pineal parenchymal tumors: clinical and therapeutic aspects

The aim of our study was to investigate the correlation of the clinical characteristic of pineal parenchymal tumors in children and adolescent with histopathological diagnosis and patient survival. Records of 27 patients with histologically diagnosed pineocytomas (n = 16) and pineoblastoma (n = 11) consecutively treated between 1991 and 2001 were reviewed retrospectively to identify factors predictive of aggressiveness. Among analyzed epidemiological, clinical, and radiological factors, we found that independent prognostic indicator in patients with childhood pineal parenchymal tumor was the extent of surgical resection.

Concentration of gelatinases and their tissue inhibitors in pancreatic inflammatory and neoplastic tumors and their influence on the early postoperative course.

UNLABELLED Pancreatic cancer (PC) is the fourth leading cause of death in the world, due to neoplastic disease. Chronic pancreatitis (CP) is a progressive disease leading towards pancreatic fibrosis. The aim of the study was to assess the impact of matrix metalloproteinases 2 and 9 (MMP2 and 9) and their tissue inhibitor (TIMP 1 and 2) concentrations in case of PC and CP tissue homogenates on early treatment results of patients subject to pancreatic resections. MATERIAL AND METHODS The study group comprised 63 patients, including 25 (39.68%) female and 38 (60.32%) male patients. Group 1 (CP) consisted of 31 patients with CP (F: M = 10/21). Group 2 (PC) consisted of 32 patients with PC (F: M = 15:17). The pancreatic tumor samples were collected from the resected pancreas, being subject to electrophoresis and immunoenzymatic studies. After confirming their activity, MMP2, MMP9, TIMP1, TIMP2 concentrations were determined. Correlation analysis of MMPs and TIMPs concentrations was performed in relation to the following: tumor diameter, age, BMI, hospitalization, duration of symptoms and surgery, blood loss, incidence of perioperative complications. RESULTS Group differences were presented in terms of: age, BMI, ASA, duration of symptoms, jaundice, tumor diameter, time of operation. There were no differences considering weight loss, blood loss, extent of resection, and hospitalization. Significant MMPs and TIMPs concentration differences between groups were demonstrated. CONCLUSIONS Comparison of PC to CP tissue samples showed significantly higher levels of metalloproteinases and TIMPs in the former. Positive correlations of MMP1, TIMP1 and 2 with tumor diameter (CP) were observed, and MMP2 with the duration of surgery and blood loss (PC). There was no MMPs and TIMPs concentration levels influence on the incidence of postoperative complications.

APP/SOD1 overexpressing mice present reduced neuropathic pain sensitivity

There are controversies regarding pain expression in mentally disabled people, including Down syndrome patients. The aim of this study was to examine neuropathic pain-related behavior and peripheral nerve regeneration in mouse model of Down syndrome. Sciatic nerves of double transgenic mice, overexpressing both amyloid precursor protein (APP) and Cu/Zn superoxide dismutase (SOD1) genes, and FVB/N wild type mice were transected and immediately resutured. Evaluation of autotomy and functional recovery was carried out during 4-week follow-up. We found markedly less severe autotomy in transgenic animals, although the onset of autotomy was significantly delayed in control mice. Interestingly, neuroma formation at the injury site was significantly more prominent in transgenic animals. Sciatic function index outcome was better in transgenic mice than in wild-type group. Histological evaluation revealed no statistically significant differences in the number of GAP-43-positive growth cones and macrophages in the distal stump of the transected nerve between groups. However, in transgenic animals, the regenerating axons were arranged more chaotically. The number of Schwann cells in the distal stump of the transected nerves was significantly lower in transgenic mice. The number of surviving motoneurons was markedly decreased in transgenic group. We measured also the atrophy of denervated muscles and found it decreased in APP/SOD1 overexpressing mice. Taken together, in this model of Down syndrome, we observed increased neuroma formation and decreased autotomy after peripheral nerve injury. Our findings suggest that APP/SOD1 overexpressing mice are less sensitive for neuropathic pain associated with neuroma.

Schwann cells in therapy of spinal cord injuries

Schwann cells (SC) have a special activity in the repair processes after injury of the nervous system because of the capability of differentiation, migration, proliferation and myelinization of axons. They enhance production of numerous neurotrophic factors, thus creating a permissive environment for axonal regeneration. Experimental studies using SC in neuronal transplants showed that these cells with their basal membrane with adhesion molecules are attractive material for neural prostheses facilitating axon growth. Moreover, SC can produce stable myelin, restoring normal function of the neuron. Transplantations of SC in myelin injury have been used in animal models of multiple sclerosis, Parkinsons disease, and brain and spinal cord injuries. Because the transplanted SC have no ability to migrate within the normal nervous system, in many experiments SC derived from rat embryos were applied. Such cells migrated through normal nervous tissue and co-operated with host cells, their survival was longer, and myelin was not destroyed in multiple sclerosis. Also, fast recovery of motor activity in injured axons in rat spinal cord was observed, especially after transplantation of SC derived from skin progenitor cells or progenitor cells which have a phenotype characteristic for SC. Many authors have reported early apoptosis of transplanted SC, so a more complex repair strategy is needed that combines SC transplantation with other methods in order to achieve longer survival and optimal functional recovery following spinal cord injury.

The neuroprotective effect of N-acetylcysteine in spinal cord-injured rats

BACKGROUND Spinal cord injury (SCI) is an important cause of impairment of sensory and motor nerve function. It has been shown that free-radical species play an important role in the pathogenesis of acute tissue trauma after SCI. There are no proven pharmacological therapies that provide neuroprotection and stimulate axonal growth after trauma. OBJECTIVES The aim of this study was to investigate the neuroprotective effect of N-acetylcysteine (NAC) on the regeneration of spinal cord injuries in rats. MATERIAL AND METHODS A total of 20 male Wistar C rats were subjected to SCI and divided into control and experimental groups. In the control group (n = 10) trepanation and SCI by means of a pressure impactor was performed without any therapy. In the study group (n = 10), 1 dose of NAC was applied intraperitoneally (150 mg/kg b.w.) immediately after SCI, and another one after 24 h. The functional outcome on the Basso-Beattie-Bresnahan (BBB) scale and sciatic functional index (SFI) and morphological features of regeneration were analyzed during a 12-week follow-up. The spinal cords and brains were collected 12 weeks after SCI for histopathological and immunohistochemical analyses. RESULTS The rats treated with NAC presented some improvement in locomotor activity and spinal cord morphology when compared to the control group. Namely, the hind paw angle of rotation was significantly lower in the NAC group than in the control group. No differences were observed between the control and study groups in terms of interlimb coordination. The area of the main lesion was only slightly decreased in the NAC group as compared to the control group. The length of lesions in the injured spinal cord in the NAC group was diminished in comparison to the control group. The number of FG-positive cells was higher in the NAC group than in the control group. CONCLUSIONS The study showed that the neuroprotective activity of NAC had limited positive influence on the regeneration of the isolated SCI in rats.