Effects of Pterional and Osteoplastic Craniotomy on Temporalis Muscle and Calvarial Bone Graft Atrophy.

This study aims to compare the effects of osteoplastic craniotomy on temporalis muscle and bone graft atrophy in patients operated on with a pterional approach to the standard technique. Patients operated on for an intracranial aneurysm with a pterional approach between 2014 and 2018 were studied. Following the exclusion criteria, 36 patients were included in this retrospective study. Temporalis muscle volume and bone graft volume were calculated. The volumes were compared from preoperative and postoperative computed tomography images for temporalis muscle and from early and late postoperative computed tomography images for the bone graft. The osteoplastic craniotomy group (group I) had 17 patients, and the standard craniotomy group had 19 patients (group II). Temporalis muscle volume and bone graft volume decreased statistically significantly in group II after surgery. However, no significant volume difference was found in group I measurements. When compared with the standard technique, osteoplastic craniotomy reduces the likelihood of postoperative temporalis muscle and bone graft atrophy in patients undergoing pterional craniotomy. As a result, the patients' cosmetic and functional well-being is improved.

A novel surgical technique for treatment of symptomatic Tarlov cysts.

BACKGROUND: The aim of this retrospective study was to describe a novel, simple surgical technique for the treatment of symptomatic Tarlov cysts. METHODS: A total of 40 patients with symptomatic Tarlov cysts, admitted to our tertiary center between 1998 and 2019 constituted the study group. All patients underwent microsurgical puckering of the cyst, the technique we described to prevent a recurrence. Patients' symptoms, radiological findings, intraoperative findings, and clinical results were evaluated. RESULTS: Of the 40 patients (5 males, 35 females) whose charts were reviewed, the mean age was 28.4 (range, 17-61) years. The mean follow-up was 8 (range, 3 months to 21 years) years. Preoperatively, the most common symptoms were leg pain and numbness of the lower extremity. Postoperatively, no major complications were observed. Clinical progression was halted in all patients; 33 (82%) patients recovered completely and seven (17%) patients reported partial recovery. Cystic cavity persisted radiologically in five (12%) patients, decreased in size in 30 (75%) patients, and regressed completely in the remaining five (12%) patients. None of the patients had permanent neurological deficits. CONCLUSION: Puckering of the cyst membrane is a safe and easy-to-perform surgical technique for symptomatic Tarlov cysts. This technique can be used almost in all cases instead of the commonly used microsurgical cyst excision or cyst fenestration.

Quantifying Neurological Examination in 21st Century: Yilmaz- Ilbay Plantar Flexion Test, A Novel and Reliable Test for Evaluation of Plantar Flexion in L5-S1 Disc Herniation.

Background: Current methods used to measure the muscle strength required to achieve plantar flexion may yield highly variable results depending on the perception of the physician conducting the examination because these tests involve subjective and qualitative evaluation. Objective: To describe and evaluate the efficacy of a novel examination technique that can quantitatively measure plantar flexion in L5-S1 disc herniation. Materials and Methods: A total of 32 patients (average age: 49.4 years, range: 23-78) with L5-S1 disc herniations were included. The patient to be tested stood next to a table on which they could lean with their hands. The leg closer to the table was fully flexed at the knee, and the other foot was brought to maximum plantar flexion on the toes. At this point, a stopwatch was started to measure the time that passed until the muscles fatigued and the heel fell. The differences between the right and left plantar flexion times were noted. In addition, three different physicians graded muscle strength by using the classical "The Medical Research Council of the United Kingdom" method. Results: The time until fatigue in right and left plantar flexion was measured using the proposed method, and each test underwent a video recording. The Yilmaz-Ilbay plantar flexion test yielded the correct classification for all cases. Conclusion: We suggest that the proposed method "Yilmaz-Ilbay plantar flexion test" can serve as a useful, practical, and effective test to detect quantitative evaluation of plantar flexion in L5-S1 herniation.

Transforaminal Vertebroplasty for Screwed Vertebrae: A New Minimally Invasive Technique.

OBJECTIVE: Pedicle screw loosening and fractures of instrumented vertebrae are not uncommon and require reoperations, which are an immense burden on the patient and health care system. We aimed to describe a novel, simple percutaneous technique on instrumented vertebrae for treating pedicle screw loosening and demonstrate that corpus with osteoporotic vertebral compression fractures can be managed with this simple technique. METHODS: This retrospective study was performed using data gathered from 15 patients who underwent transforaminal vertebroplasty due to symptomatic pedicle screw loosening and vertebral body fracture between 2020 and 2021. Patients' symptoms, radiologic findings, intraoperative findings, and clinical outcomes were noted. RESULTS: This series consisted of 5 male and 10 female patients, and the mean duration of follow-up was 8 months (range: 3 to 13). The average age was 66.67 ± 4.59 years (range: 55-72). Preoperatively, symptoms were leg pain, numbness of the lower extremity, and back pain. Postoperatively, no major complications were observed. Clinical progression of pedicle screw loosening and osteoporotic vertebral compression fractures were halted in all patients. None of the patients had permanent neurologic deficits. All the patients reported a dramatic decrease in pain immediately after the procedure. The vertebral fracture was detected in 3 patients, and screw loosening occurred in 12 patients. All symptoms resolved during follow-up. CONCLUSIONS: Our preliminary results imply that transforaminal vertebroplasty is a safe and easy percutaneous technique in symptomatic pedicle screw loosening and osteoporotic vertebral compression fractures in the instrumented vertebrae. Further trials on larger series are necessary to validate our data.

Methylation Profiling of Specific Genes in Ependymomas.

OBJECTIVE: Ependymomas are neuroepithelial tumors of the central nervous system with heterogeneous biology and clinical course. The aim of the present study is to investigate the relationship between the methylation status and clinicopathological parameters in ependymomas. MATERIAL AND METHOD: DNA methylation status of CDKN2A, RASSF1A, KLF4 and ZIC2 genes were quantitatively analyzed with pyrosequencing in 44 ependymoma tumor tissues. The relationship of methylation profiles with tumor subtype, histological grade and patient age was statistically analyzed. RESULTS: DNA methylation analyses for CDKN2A revealed no difference in methylation levels. Of the 31 included samples for optimal ZIC2 methylation analysis, 10 were hypermethylated (32.3%) and this change was significantly found in the adult spinal ependymomas (p=0.01). KLF4 hypermethylation was observed in 6 of the overall included 35 samples (17.1%); however, there was no statistically significant relation of the methylation status with tumor subtype, histological grade or age group. RASSF1A hypermethylation was observed in overall 40 included samples with varying methylation levels. Higher levels of hypermethylation were significantly related to the grade 3 histology (p=0.01) and spinal ependymomas (p=0.006). The pediatric cases with grade 3 ependymomas and ependymomas of adulthood showed significantly increased RASSF1A hypermethylation levels (p < 0.001 and p=0.001, respectively). CONCLUSION: DNA methylation changes are likely to have biological importance in ependymomas. Both ZIC2 and RASSF1A methylation status may be useful parameters in the subclassification of these tumors.

Quantitative Analysis of Serum Zinc Levels in Primary Brain Tumor Patients.

Although the close relationships between most of the trace elements and tumor formation mechanisms are very well-defined, studies on some elements such as zinc are still ongoing. When examining studies on brain tumors, it was observed that studies investigating the role played by serum zinc levels on tumor etiology and prognosis have gained momentum. In this study, we investigate the relationship between different brain tumor types and serum zinc levels by quantitatively analyzing serum zinc levels in patients with primary brain tumors. In this study, we measured serum zinc levels of 33 brain tumor patients as well as 35 healthy individuals serving as a control group. Metal concentrations were measured using atomic absorption spectrophotometry. Serum zinc levels were lower in patients with primary brain tumors compared to control group (p < 0.05). Additionally, patients' serum zinc levels were significantly different according to their brain tumor types and also according to their age (p < 0.05). Our findings suggest that brain tumor patients' serum zinc levels may play a role in tumor etiology, typology, and prognosis.

The effects of intra-cerebroventricular administered rocuronium on the central nervous system of rats and determination of its epileptic seizure-inducing dose / Efeitos da administração intracerebroventricular de rocurônio sobre o sistema nervoso central de ratos e determinação da dose indutora de crise epiléptica

Abstract Background: The aim of this study was to investigate the effects of intracerebroventricularly administered rocuronium bromide on the central nervous system, determine the seizure threshold dose of rocuronium bromide in rats, and investigate the effects of rocuronium on the central nervous system at 1/5, 1/10, and 1/100 dilutions of the determined seizure threshold dose. Methods: A permanent cannula was placed in the lateral cerebral ventricle of the animals. The study was designed in two phases. In the first phase, the seizure threshold dose of rocuronium bromide was determined. In the second phase, Group R 1/5 (n = 6), Group 1/10 (n = 6), and Group 1/100 (n = 6) were formed using doses of 1/5, 1/10, and 1/100, respectively, of the obtained rocuronium bromide seizure threshold dose. Results: The rocuronium bromide seizure threshold value was found to be 0.056 ± 0.009 µmoL. The seizure threshold, as a function of the body weight of rats, was calculated as 0.286 µmoL/kg-1. A dose of 1/5 of the seizure threshold dose primarily caused splayed limbs, posturing, and tremors of the entire body, whereas the dose of 1/10 of the seizure threshold dose caused agitation and shivering. A dose of 1/100 of the seizure threshold dose was associated with decreased locomotor activity. Conclusions: This study showed that rocuronium bromide has dose-related deleterious effects on the central nervous system and can produce dose-dependent excitatory effects and seizures.

Resumo Justificativa: O objetivo deste estudo foi investigar os efeitos do brometo de rocurônio administrado intracerebroventricularmente sobre o sistema nervoso central, determinar a dose do limiar convulsivo de rocurônio em ratos e investigar os efeitos de rocurônio no sistema nervoso central em diluições de 1/5, 1/10 e 1/100 da dose do limiar convulsivo determinada. Métodos: Uma cânula permanente foi colocada no ventrículo lateral do cérebro dos animais. O estudo foi projetado em duas fases. Na primeira, a dose do limiar convulsivo do brometo de rocurônio foi determinada. Na segunda, o Grupo R 1/5 (n = 6), o Grupo 1/10 (n = 6) e Grupo 1/100 (n = 6) foram formados com doses de 1/5, 1/10 e 1/100, respectivamente, da dose do limiar convulsivo de brometo de rocurônio obtida. Resultados: Descobrimos que o valor do limiar convulsivo de brometo de rocurônio é 0,056 ± 0,009 µmoL. O limiar convulsivo, como uma função do peso corporal dos ratos, foi calculado como 0,286 µmoL/kg-1. Uma dose de 1/5 da dose do limiar convulsivo causou principalmente abertura postural dos membros e tremores em todo o corpo, enquanto uma dose de 1/10 da dose do limiar convulsivo causou agitação e tremores. Uma dose de 1/100 da dose do limiar convulsivo foi associada à diminuição da atividade locomotora. Conclusões: Este estudo mostrou que o brometo de rocurônio tem efeitos deletérios relacionados com a dose sobre o sistema nervoso central e pode produzir efeitos excitatórios dependentes da dose e convulsões.

[The effects of intra-cerebroventricular administered rocuronium on the central nervous system of rats and determination of its epileptic seizure-inducing dose]. / Efeitos da administração intracerebroventricular de rocurônio sobre o sistema nervoso central de ratos e determinação da dose indutora de crise epiléptica.

BACKGROUND: The aim of this study was to investigate the effects of intracerebroventricularly administered rocuronium bromide on the central nervous system, determine the seizure threshold dose of rocuronium bromide in rats, and investigate the effects of rocuronium on the central nervous system at 1/5, 1/10, and 1/100 dilutions of the determined seizure threshold dose. METHODS: A permanent cannula was placed in the lateral cerebral ventricle of the animals. The study was designed in two phases. In the first phase, the seizure threshold dose of rocuronium bromide was determined. In the second phase, Group R 1/5 (n=6), Group 1/10 (n=6), and Group 1/100 (n=6) were formed using doses of 1/5, 1/10, and 1/100, respectively, of the obtained rocuronium bromide seizure threshold dose. RESULTS: The rocuronium bromide seizure threshold value was found to be 0.056±0.009µmoL. The seizure threshold, as a function of the body weight of rats, was calculated as 0.286µmoL/kg-1. A dose of 1/5 of the seizure threshold dose primarily caused splayed limbs, posturing, and tremors of the entire body, whereas the dose of 1/10 of the seizure threshold dose caused agitation and shivering. A dose of 1/100 of the seizure threshold dose was associated with decreased locomotor activity. CONCLUSIONS: This study showed that rocuronium bromide has dose-related deleterious effects on the central nervous system and can produce dose-dependent excitatory effects and seizures.

The effects of intra-cerebroventricular administered rocuronium on the central nervous system of rats and determination of its epileptic seizure-inducing dose.

BACKGROUND: The aim of this study was to investigate the effects of intracerebroventricularly administered rocuronium bromide on the central nervous system, determine the seizure threshold dose of rocuronium bromide in rats, and investigate the effects of rocuronium on the central nervous system at 1/5, 1/10, and 1/100 dilutions of the determined seizure threshold dose. METHODS: A permanent cannula was placed in the lateral cerebral ventricle of the animals. The study was designed in two phases. In the first phase, the seizure threshold dose of rocuronium bromide was determined. In the second phase, Group R 1/5 (n=6), Group 1/10 (n=6), and Group 1/100 (n=6) were formed using doses of 1/5, 1/10, and 1/100, respectively, of the obtained rocuronium bromide seizure threshold dose. RESULTS: The rocuronium bromide seizure threshold value was found to be 0.056±0.009µmoL. The seizure threshold, as a function of the body weight of rats, was calculated as 0.286µmoL/kg-1. A dose of 1/5 of the seizure threshold dose primarily caused splayed limbs, posturing, and tremors of the entire body, whereas the dose of 1/10 of the seizure threshold dose caused agitation and shivering. A dose of 1/100 of the seizure threshold dose was associated with decreased locomotor activity. CONCLUSIONS: This study showed that rocuronium bromide has dose-related deleterious effects on the central nervous system and can produce dose-dependent excitatory effects and seizures.

Cardioprotective Effects of Remifentanil in a Sympathetic Hyperactivity Model in Rabbits.

OBJECTIVE: In this study, the antiarrhythmic and anti-ischemic effects of a 6 µg kg(-1) min(-1) infusion dose of remifentanil are investigated in a central sympathetic hyperactivity model in rabbits. METHODS: In this study, 18 New Zealand rabbits were used. The subjects were randomly divided into three groups (n=6) and received 10 µmol L(-1) glutamate intracerebroventricularly to provide the central sympathetic hyperactivity. In group 1, 10 µmol L(-1) glutamate was used; in group 2, 1 h before L-glutamate injection, 40 mg kg(-1) N (omega)-nitro-L-arginine methyl ester was intravenously (iv) administered; and in group 3, also 1 h before L-glutamate injection, 40 mg kg(-1) N (omega)-nitro-L-arginine methyl ester was iv administered. A 6 µg kg(-1) min(-1) dose of remifentanil infusion was administered 5 min before L-glutamate injection. Heart rate, systolic arterial pressure and mean arterial pressure were measured and recorded. Within 15 min of the intracerebroventricular L-glutamate injection, premature ventricular complexes, bigeminy ventricular arrhythmia, ventricular tachycardia, ST-segment shift and T-wave inversions were recorded. RESULTS: When incidences of heart rate, rate pressure product, premature ventricular complexes and bigeminy ventricular arrhythmia were compared between groups, significant differences were not determined. Mean arterial pressure was more significantly increased in group 2 than in the other groups (p<0.05). Ventricular tachycardia, ST-segment shift and T-wave inversions were significantly lower in group 3 than in groups 1 and 2 (p<0.05). CONCLUSION: Remifentanil (6 µg kg(-1) min(-1) for 5 min of infusion) prevented life-threatening ventricular tachycardia and electrocardiographic signs of myocardial ischemia in a model of arrhythmia resulting from the association of central sympathetic overactivity.

Experimental traumatic spinal cord injury.

Animal models are important to develop therapies for individuals suffering from spinal cord injuries. For this purpose, rats are commonly preferred. In sharp injury models, spinal cord is completely or incompletely cut to assess axonal regeneration. On the other hand, spinal cord is compressed or contused to mimic the human injury in blunt injury models for understanding as well as managing the secondary pathophysiologic processes following injury. Especially, contusions are thought to be biomechanically similar to vertebral fractures and/or dislocations and thus provide the most realistic experimental setting in which to test potential neuroprotective and regenerative strategies.

Erythropoietin-induced changes in brain gene expression reveal induction of synaptic plasticity genes in experimental stroke.

Erythropoietin (EPO) is a neuroprotective cytokine in models of ischemic and nervous system injury, where it reduces neuronal apoptosis and inflammatory cytokines and increases neurogenesis and angiogenesis. EPO also improves cognition in healthy volunteers and schizophrenic patients. We studied the effect of EPO administration on the gene-expression profile in the ischemic cortex of rats after cerebral ischemia at early time points (2 and 6 h). EPO treatment up-regulated genes already increased by ischemia. Hierarchical clustering and analysis of overrepresented functional categories identified genes implicated in synaptic plasticity-Arc, BDNF, Egr1, and Egr2, of which Egr2 was the most significantly regulated. Up-regulation of Arc, BDNF, Dusp5, Egr1, Egr2, Egr4, and Nr4a3 was confirmed by quantitative PCR. We investigated the up-regulation of Egr2/Krox20 further because of its role in neuronal plasticity. Its elevation by EPO was confirmed in an independent in vivo experiment of cerebral ischemia in rats. Using the rat neuroblastoma B104, we found that wild-type cells that do not express EPO receptor (EPOR) do not respond to EPO by inducing Egr2. However, EPOR-expressing B104 cells induce Egr2 early upon incubation with EPO, indicating that Egr2 induction is a direct effect of EPO and that EPOR mediates this effect. Because these changes occur in vivo before decreased inflammatory cytokines or neuronal apoptosis is evident, these findings provide a molecular mechanism for the neuroreparative effects of cytokines and suggest a mechanism of neuroprotection by which promotion of a plastic phenotype results in decreased inflammation and neuronal death.

The effect of TENS on pain, function, depression, and analgesic consumption in the early postoperative period with spinal surgery patients.

AIM: The aim of our study was to examine the effects of the use of Transcutaneous Electrical Nerve Stimulation (TENS) in patients who had undergone spinal surgery on pain, functionality, depression and consumption of analgesic agents. MATERIAL AND METHODS: Fifty-Four patients were randomized and placed into two groups, patient-controlled analgesia (PCA) plus TENS and only PCA. To assess the pain levels of the patients, the Visual Analog Scale (VAS) was used. In the assessment of their functional levels, the Timed Up and Go test (TUG) was utilized and in the assessment of their depression, the Beck Depression Inventory (BDI) was used. The measurements were performed before the operation and on the first and second postoperative days. The side effects were recorded from the analgesic agents. RESULTS: During the first and second days after the operation, a decrease in the pain levels was noticed in the TENS group (p < 0.05. In the TENS group, the consumption of analgesic agents also decreased and thus side effects were less frequent. From the viewpoint of functional and depression levels, no significant difference between the groups was noticed (p > 0.05). CONCLUSION: TENS was effective in reducing analgesic agent-related side effects and in reducing analgesic consumption. In addition, TENS also decreased activity related pain.

Nonerythropoietic tissue protective compounds are highly effective facilitators of wound healing.

Erythropoietin (EPO) is a type I cytokine that utilizes different receptor isoforms either to maintain hematopoiesis or protect against injuries that arise from widely diverse etiologies. EPO also facilitates healing by reducing inflammation and mobilizing endothelial progenitor cells to participate in restorative neoangiogenesis, but it is unclear which EPO receptor isoform is responsible for healing and whether this receptor use varies according to the type of wound. In the present studies carried out in the rat, we have utilized receptor-selective derivatives of EPO to determine which receptor type operates in (i) a nonischemic wound (skin punch biopsy), (ii) a permanently ischemic wound (raised musculocutaneous flap), (iii) an intermittent ischemic reperfusion wound (pressure or decubitus ulcer), or (iv) wounds complicated by infection (cecal ligation and perforation). Using these models, we demonstrate that nonerythropoietic tissue protective compounds administered immediately following injury limit wound size and accelerate eschar closure independent of wound type. Moreover, in a model of peritonitis-induced adhesions, daily administration of the nonerythropoietic derivative carbamyl-EPO (10 microg/kg-bw) was associated with significantly lower serum TNFalpha concentration, illness scores, increased survival, as well as decreased adhesion formation. These results confirm that wound healing is mediated by the tissue protective receptor isoform and argue that nonerythropoietic tissue protective molecules constitute promising new.

Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin.

Erythropoietin (EPO), a member of the type 1 cytokine superfamily, plays a critical hormonal role regulating erythrocyte production as well as a paracrine/autocrine role in which locally produced EPO protects a wide variety of tissues from diverse injuries. Significantly, these functions are mediated by distinct receptors: hematopoiesis via the EPO receptor homodimer and tissue protection via a heterocomplex composed of the EPO receptor and CD131, the beta common receptor. In the present work, we have delimited tissue-protective domains within EPO to short peptide sequences. We demonstrate that helix B (amino acid residues 58-82) of EPO, which faces the aqueous medium when EPO is bound to the receptor homodimer, is both neuroprotective in vitro and tissue protective in vivo in a variety of models, including ischemic stroke, diabetes-induced retinal edema, and peripheral nerve trauma. Remarkably, an 11-aa peptide composed of adjacent amino acids forming the aqueous face of helix B is also tissue protective, as confirmed by its therapeutic benefit in models of ischemic stroke and renal ischemia-reperfusion. Further, this peptide simulating the aqueous surface of helix B also exhibits EPO's trophic effects by accelerating wound healing and augmenting cognitive function in rodents. As anticipated, neither helix B nor the 11-aa peptide is erythropoietic in vitro or in vivo. Thus, the tissue-protective activities of EPO are mimicked by small, nonerythropoietic peptides that simulate a portion of EPO's three-dimensional structure.

The physical activity of patients after herniated lumbar disc surgery.

OBJECTIVE: We evaluated the level of pain, disability, performance, and physical activity changes in patients who underwent lumbar disc hernia surgery. METHODS: This study included 31 patients who underwent lumbar disc hernia surgery in the Neurosurgery Department of Dokuz Eylul University Hospital, Izmir, Turkey over a 13-month period from April 2003 to May 2004. Changes in the patients` pain were determined using a visual analog scale, and disability changes were evaluated using the Oswestry Disability Index. Total times for the following performance tests were recorded: rolling from right to left and vice versa, loaded reach, repeated sitting/standing, 50-foot walk, and 5-min walk. The Compendium of Physical Activities questionnaire was used to assess physical activity levels in a 24-hour period. The assessments were performed 2, 4, and 6 months postoperatively. RESULTS: Significant differences were observed in the pain, disability, performance, and physical activity levels 2, 4, and 6 months postoperatively (p=0.000), with the worst values at 2 months and the best at 6 months. CONCLUSION: A need exists not only to direct patients toward more active lifestyles and physical fitness, but also to use assessments to accelerate the recovery period, ensuring continuity in the postoperative period.

Erythropoietin protects the intestine against ischemia/ reperfusion injury in rats.

Previous studies have shown that erythropoietin (EPO) has protective effects against ischemia/reperfusion (I/R) injury in several tissues. The aim of this study was to determine whether EPO could prevent intestinal tissue injury induced by I/R. Wistar rats were subjected to intestinal ischemia (30 min) and reperfusion (60 min). A single dose of EPO (5000 U/kg) was administered intraperitoneally at two different time points: either at five minutes before the onset of ischemia or at the onset of reperfusion. At the end of the reperfusion period, jejunum was removed for examinations. Myeloperoxidase (MPO), malondialdehyde (MDA), and antioxidant defense system were assessed by biochemical analyses. Histological evaluation was performed according to the Chiu scoring method. Endothelial nitric oxide synthase (eNOS) was demonstrated by immunohistochemistry. Apoptotic cells were determined by TUNEL staining. Compared with the sham, I/R caused intestinal tissue injury (Chiu score, 3+/-0.36 vs 0.4+/-0.24, P<0.01) and was accompanied by increases in MDA levels (0.747+/-0.076 vs 0.492+/-0.033, P<0.05), MPO activity (10.51+/-1.87 vs 4.3+/-0.45, P<0.05), intensity of eNOS immunolabelling (3+/-0.4 vs 1.3+/-0.33, P<0.05), the number of TUNEL-positive cells (20.4+/-2.6 vs 4.6+/-1.2, P<0.001), and a decrease in catalase activity (16.83+/-2.6 vs 43.15+/-4.7, P<0.01). Compared with the vehicle-treated I/R, EPO improved tissue injury; decreased the intensity of eNOS immunolabelling (1.6+/-0.24 vs 3+/-0.4, P<0.05), the number of TUNEL-positive cells (9.2+/-2.7 vs 20.4+/-2.6, P<0.01), and the high histological scores (1+/-0.51 vs 3+/-0.36, P<0.01), and increased catalase activity (42.85+/-6 vs 16.83+/-2.6, P<0.01) when given before ischemia, while it was found to have decreased the levels of MDA (0.483+/-0.025 vs 0.747+/-0.076, P<0.05) and MPO activity (3.86+/-0.76 vs 10.51+/-1.87, P<0.05), intensity of eNOS immunolabelling (1.4+/-0.24 vs 3+/-0.4, P<0.01), the number of TUNEL-positive cells (9.1+/-3 vs 20.4+/-2.6, P<0.01), and the number of high histological scores (1.16+/-0.4 vs 3+/-0.36, P<0.05) when given at the onset of reperfusion. These results demonstrate that EPO protects against intestinal I/R injury in rats by reducing oxidative stress and apoptosis. We attributed this beneficial effect to the antioxidative properties of EPO.

Carbamylated erythropoietin reduces radiosurgically-induced brain injury.

Gamma knife radiosurgery is an attractive noninvasive treatment of brain tumors and vascular malformations that minimizes collateral tissue damage. However, exposure of normal tissue to even low-dose radiation triggers a cascade of acute and chronic injury and potentially significant morbidity and mortality. Because many irradiated patients now survive for years, identifying methods to prevent radiotherapy-induced collateral tissue damage is a major focus of current research. Erythropoietin (EPO), a cytokine produced locally by many tissues in response to injury, antagonizes apoptosis, reduces inflammation, and promotes healing. Systemic administration of recombinant EPO, widely used for treatment of anemia, provides robust protection from numerous insults in a variety of tissues, including the brain. Although irradiation injury is likely sensitive to EPO, the hematopoietic activity of EPO is undesirable in this setting, increasing erythrocyte number and predisposing to thrombosis. To avoid these potential adverse effects, we developed carbamylated EPO (CEPO) which does not stimulate the bone marrow. In this study, we show that CEPO (50 microg kg(-1) intraperitoneally) improves functional outcome when administered to adult rats just before, and then once daily for 10 d after, a necrotizing dose of radiation (100 Gy) to the right striatum. Immediately following irradiation, use and reflex movements of the contralateral forelimb to vibrissae stimulation were abnormal but rapidly improved in animals receiving CEPO. Moreover, histological examination revealed that the extent of brain necrosis after 90 days was reduced by approximately 50%. These findings further extend the kinds of injury for which administration of a tissue-protective cytokine provides benefit.