Antioxidant and anti-inflammatory potential of crocin on the doxorubicin mediated hepatotoxicity in Wistar rats.

Doxorubicin (DXR) is widely used in cancer treatment. However, it has not yet been possible to prevent the side effects of DXR. The aim of this study was to investigate the hepatoprotective effect of crocin against DXR used in cancer treatment. For this reason; forty Wistar rats (male-250-300 g) were allocated into four groups (n = 10/group): Control, Crocin, DXR and DXR+Crocin. Control and Crocin groups were administered saline and crocin (40 mg/kg, i.p) for 15 days, respectively. DXR group, cumulative dose 12 mg/kg DXR, was administered for 12 days via 48 h intervals in six injections (2 mg/kg each, i.p). DXR+Crocin group, crocin (40 mg/kg-i.p) was administered for 15 days, and DXR was given as in the DXR group. The results revealed that serum liver markers (alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) increased significantly after DXR administration but recovered after crocin therapy. In addition, lipid peroxidation (MDA), and inflammatory cytokine (TNF-α) increased after DXR application and the antioxidative defense system (GSH, SOD, CAT) significantly decreased and re-achieved by crocin treatment. Our results conclude that crocin treatment was related to ameliorated hepatocellular architecture and reduced hepatic oxidative stress and inflammation in rats with DXR-induced hepatotoxicity.

Follicular fluid redox balance and DNA damage according to PCOS phenotype.

OBJECTIVE: Classification of polycystic ovary syndrome (PCOS) according to their phenotypes is important in terms of understanding which parameter has clinical and laboratory implications. This study was designed to measure the follicular fluid total oxidant capacity (TOC) and total antioxidant capacity (TAC) and DNA degradation products of 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in patients with different PCOS phenotypes undergoing In-Vitro Fertilization/Intra-Cytoplasmic Sperm Injection (IVF/ICSI). PATIENTS AND METHODS: Thirty women who were diagnosed with PCOS and twenty infertile patients who did not have the clinical and laboratory findings of PCOS were included. Women carrying at least two of the three parameters below were considered to have PCOS. (1) Biochemical or clinical manifestations of hyperandrogenism (HA); (2) Ovulatory dysfunction (OD); (3) Polycystic ovarian morphology (PCOM). Patients were then classified into four different PCOS phenotypes: (1) Phenotype A is also known as classical PCOS and meets all three criteria (HA/OD/PCOM). (2) Phenotype B has two criteria, HA and OD. (3) Phenotype C consists of HA and PCOM criteria. (4) Phenotype D is the non-hyperandrogenic form and consists of OD and PCOM criteria. Antagonist protocol was used in both PCOS and control groups. During oocyte pick-up, follicular fluid of the dominant follicle was collected. TAC and TOC levels, which are redox balance markers, and 8-OHdG levels, which are DNA degradation products, were measured in follicular fluid samples (FF). RESULTS: Follicular fluid 8-OHdG levels of all four types of phenotypes were significantly higher than the control group. When the phenotype groups were evaluated among themselves, FF-8-OHdG levels of each group were found to be similar. Serum TOC levels of each phenotype group were found to be significantly higher than the control group. TAC levels of the patients in the control group were significantly higher than the other four phenotype groups. Oxidative stress index (OSI) values were significantly higher in all four phenotype groups compared to the control group. OSI values of phenotype B and D groups were significantly higher than phenotypes A and C. CONCLUSIONS: In each phenotype of PCOS, TOC and OSI increased while TAC decreased. Increased OSI leads to DNA degradation and an increase in the level of 8-OHdG. The cumulative effect of oxidative stress and DNA degradation may be the main mechanism of PCOS-related subfertility.

Impact of body mass index and vitamin D on serum AMH levels and antral follicle count in PCOS.

OBJECTIVE: To investigate the effects of body mass index (BMI) values and 25(OH) vitamin D levels determined by Endocrine Society on serum Anti Mullerian Hormone (AMH) and antral follicle count (AFC) in women with polycystic ovary syndrome (PCOS). PATIENTS AND METHODS: Sixty infertile women with PCOS and 30 age-matched women with unexplained infertility (UEI), were included. Patients in PCOS and control groups were divided into three subgroups according to their BMI values as normal, overweight and obese. Each BMI group was divided into three subgroups according to vitamin D levels. While AMH and vitamin D levels were determined at first admission, AFC was measured on the third day of cycle. RESULTS: BMI, AFC, and AMH levels of women with PCOS were significantly higher than the UEI group. AMH values of women with PCOS with normal BMI were found to be significantly higher than UEI controls with normal BMI. AMH values of overweight and obese PCOS patients and controls were similar. As BMI values of the PCOS group increased, vitamin D levels decreased significantly. Vitamin D levels of the patients in the PCOS group were found to be significantly lower than the control group. When evaluated according to BMI, the vitamin D levels of normal, overweight and obese women with PCOS were significantly lower than the UEI. CONCLUSIONS: Rising BMI in PCOS leads to a significant decrease in vitamin D and AMH. Deficiency, insufficiency or normality of vitamin D do not affect the main markers of ovarian reserve.

Continuous and intermittent parathyroid hormone administration promotes osteogenic differentiation and activity of programmable cells of monocytic origin.

Bone healing deficiencies are challenging for orthopedic practice. The use of stem cells with scaffolds to treat bone tissue losses currently is popular for promoting regeneration of tissue. Programmable cells of monocytic origin (PCMO) may differentiate into three germ layers and may be a promising alternative treatment due to their stem cell-like properties. Parathyroid hormone (PTH) participates in bone metabolism. Intermittent administration of PTH promotes osteogenic activity of mesenchymal stem cdells (MSC). We investigated the osteogenic effects of continuous and intermittent administration of PTH on PCMO. Mononuclear cells were harvested from the peripheral blood of healthy donors. Isolated cells were cultured for six days in a de-differentiation medium. Indirect immunocytochemistry using anti-CD14, anti-CD45 and anti-CD90 primary antibodies, as well as electron microscopy were used to detect PCMO. PCMO then were cultured in an osteogenic differentiation medium supplemented with continuous or intermittent 50 ng/ml PTH. The PTH-free control group (CG), intermittent PTH treated group (IPG) and continuous PTH treated group (CPG) were cultured and assessed for their differentiation into osteogenic lineage cells by indirect immunocytochemistry using anti-collagen I, anti-osteonectin and anti-osteocalcin primary antibodies. Osteoblast-like cells obtained by continuous or intermittent PTH administration exhibited increased levels of collagen I, osteonectin and osteocalcin immunoreactivity. We found that continuous and intermittent PTH administration to PCMO enhanced their differentiation to osteogenic lineage cells and increased osteoblastic activity.

Unique Distal Enhancers Linked to the Mouse Tnfsf11 Gene Direct Tissue-Specific and Inflammation-Induced Expression of RANKL.

Receptor activator of nuclear factor κB ligand (RANKL) is expressed by a number of cell types to participate in diverse physiological functions. We have previously identified 10 distal RANKL enhancers. Earlier studies have shown that RL-D5 is a multifunctional RANKL enhancer. Deletion of RL-D5 from the mouse genome leads to lower skeletal and lymphoid tissue RANKL, causing a high bone mass phenotype. Herein, we determine the physiological role and lineage specificity of 2 additional RANKL enhancers, RL-D6 and RL-T1, which are located 83 and 123 kb upstream of the gene's transcriptional start site, respectively. Lack of RL-D6 or RL-T1 did not alter skeletal RANKL or bone mineral density up to 48 weeks of age. Although both RL-D5 and RL-T1 contributed to activation induction of T-cell RANKL, RL-T1 knockout mice had drastically low lymphocyte and lymphoid tissue RANKL levels, indicating that RL-T1 is the major regulator of lymphocyte RANKL. Moreover, RL-T1 knockout mice had lower circulating soluble RANKL, suggesting that lymphocytes are important sources of circulating soluble RANKL. Under physiological conditions, lack of RL-D6 did not alter RANKL expression. However, lack of RL-D5 or RL-D6, but not of RL-T1, blunted the oncostatin M and lipopolysaccharide induction of RANKL ex vivo and in vivo, suggesting that RL-D5 and RL-D6 coregulate the inflammation-mediated induction of RANKL in osteocytes and osteoblasts while lack of RL-D6 did not alter secondary hyperparathyroidism or lactation induction of RANKL or bone loss. These results suggest that although RL-D5 mediates RANKL expression in multiple lineages, other cell type- or factor-specific enhancers are required for its appropriate control, demonstrating the cell type-specific and complex regulation of RANKL expression.

An in vivo study on the effect of scaffold geometry and growth factor release on the healing of bone defects.

The hypothesis of this study was that the extent of bone regeneration could be enhanced by using scaffolds with appropriate geometry, and that such an effect could be further increased by mimicking the natural timing of appearance of bone morphogenetic proteins BMP-2 and BMP-7 after fracture. Bioplotted poly(ε-caprolactone) (PCL) disks with four different fibre organizations were used to study the effect of 3D scaffold architecture on the healing of bone defects in a rat pelvis model. Moreover, one PCL construct was further modified by introducing a nanoparticulate sequential BMP-2/BMP-7 delivery system into this scaffold. Scaffolds and functionalized construct along with free nanocapsules were implanted using a rat iliac crest defect model. Six weeks post-implantation, the defects were evaluated by CT scan and histology. Analysis revealed that the basic architecture, having the highest pore volume for tissue ingrowth, presented the highest bone formation as determined by the bone mineral density (BMD) within the defect (144.2 ± 7.1); about four-fold higher than that of the empty defect (34.9 ± 10.7). It also showed the highest histological analysis scores with a high amount of bone formation within the defect, within the scaffold pores and along the outer surfaces of the scaffold. The basic scaffold carrying the BMP-2/BMP-7 delivery system showed significantly higher bone formation than the growth factor-free basic scaffold at 6 weeks (BMD 206.8 ± 15.7). Histological analysis also revealed new bone formation in close to or in direct contact with the construct interface. This study indicates the importance of open and interconnecting pore geometry on the better healing of bone defects, and that this effect could be further increased by supplying growth factors, as is the case in nature.

Primary diffuse choroid plexus T-cell lymphoma: case report.

We present here a case of primary choroid plexus T-cell lymphoma with no evidence of immunodeficiency or immunological disease. As ventricular T-cell lymphoma is extremely rare, there is only limited information on the radiological findings of ventricular T-cell lymphoma. In this report, we also include some unusual MRI findings in this case that have never been described before.

Etiologic factors in falls from height in pediatric cases.

OBJECTIVE: In this study, factors causing falls from height and precautions taken for their prevention were investigated. METHODS: The study was carried out prospectively between June 2009 and June 2010. Patients under 18 years of age presenting at the emergency department of a university hospital, for whom the primary reason for admission was an accidental fall from a height of at least one meter, were included in the study. The demographic characteristics of the patients, the characteristics of the falls, and clinical features were recorded. RESULTS: Data for 133 patients were evaluated. Among these patients, 72 (54.1%) were male; the median age was 4 (IQR 2-7). The most common fall site was a balcony (38%). Falls frequently happened in the spring and the summer. The mean fall height was 2.9 ± 2.5 m, the median GCS score was 15 (IQR 14-15), and the median PTS was 10 (IQR 9-11). The fall heights was higher in patients who lost consciousness (p < 0.001). Among the 95 patients who were 0-6 years old, it was found that about 55% were unaccompanied by their parents. The most common pathology in the patients was head trauma (63%), while 17.3% had multiple traumas. CONCLUSION: Since the vast majority of the fall cases were in the pre-school age group, most were due to falls from a balcony, and more than half of the cases were unaccompanied by parents or caregivers, there are two issues that need to be addressed in relation to pediatric falls from height: family education and legal regulations considering child safety in the design of doors, windows, and balconies of buildings.

Analysis of proximal radial nerve injury in the arm.

BACKGROUND: Radial nerve is the most frequently injured major nerve in the upper extremity. Proximal part of the radial nerve involvement can result from a humerus fracture, direct nerve trauma, compression and rarely from tumors. OBJECTIVES: The aim of the study is to determine the clinical characteristics and electrodiagnostic findings in patients with proximal radial nerve injuries, and also the outcome of surgical treatment. MATERIALS AND METHODS: The study subjects included 46 patients with radial nerve injuries seen between June 2000 and June 2008 at our hospital. The analysis included demographics, clinical features, etiology, pre-and postoperative EMNG (Electromyoneurography) findings. RESULTS: Surgical decompression resulted in neurological improvement in patients with radial entrapment neuropathies. Good neurological recovery was observed from decompression of callus of old humeral fracture. The worst results were observed in the direct missile injuries of the radial nerve. CONCLUSIONS: A detailed clinical and electrodiagnostic evaluation is of importance in patients with radial nerve injury to ensure an appropriate treatment. The choice of treatment, conservative or surgical, depends on the clinical presentation and the type of injury.

Cutaneous silent period changes in Type 2 diabetes mellitus patients with small fiber neuropathy.

OBJECTIVE: Small myelinated (A-delta) and unmyelinated (C) somatic sensory fibers are initially affected and may be the earliest exhibited sign of neuropathy in glucose dysmetabolism. Cutaneous silent period (CSP) is an inhibitory spinal reflex and its afferents consist of A-delta nerve fibers. The aim of this study was to evaluate CSP changes in Type 2 diabetic patients with small fiber neuropathy. METHODS: Forty-three patients and 41 healthy volunteers were included. CSP latency and duration, as well as CSP latency difference of the upper and lower extremities, were examined. RESULTS: Nerve conduction studies were within normal limits in both groups. Lower extremity CSP latency was longer (122.1+/-15.5 vs. 96.4+/-6.4 ms; p<0.001), CSP duration was shorter (29.5+/-8.9 vs. 43.1+/-5.0 ms; p<0.001), and latency difference was longer (48.1+/-12.6 vs. 22.7+/-3.7; p<0.001) in patients than controls. The difference was more significant in patients with neuropathic pain. No significant difference existed in upper extremity on CSP evaluation. CONCLUSION: The CSP evaluation together with nerve conduction study, has been demonstrated to be beneficial and performance of latency difference in addition to CSP latency and duration may be a valuable parameter in electrophysiological assessment of diabetic patients with small fiber neuropathy. SIGNIFICANCE: An additional CSP evaluation may be considered in cases which nerve conduction studies do not provide sufficient information.

Fournier's gangrene: evaluation of 68 patients and analysis of prognostic variables.

CONTEXT: Fournier's gangrene (FG) is a rapidly progressing acute gangrenous infection of the anorectal and urogenital area. AIMS: The objectives of this study were to investigate patients with FG and to determine risk factors that affect mortality. SETTINGS AND DESIGN: Retrospective clinical study. MATERIALS AND METHODS: Clinical presentations and outcomes of surgical treatments were evaluated in 68 patients with FG. STATISTICAL ANALYSIS USED: Chi-square, Student's t -test, and logistic regression test. RESULTS: Mean age of patients was 54 and female-to-male ratio was 9:59. Among the predisposing factors, diabetes mellitus (DM) was the most common ( n =24, 35.3%), and sepsis on admission was detected in 31 (45.6%) and 15 (22.1%) patients, respectively. Seven (10.3%) patients died. Using logistic regression test, Fournier's Gangrene Severity Index (FGSI)> 9, DM and sepsis on admission were found as prognostic factors. CONCLUSIONS: FG has a high mortality rate, especially in patients with DM and sepsis. An FGSI value> 9 indicates high mortality rate.

Laparoscopic cholecystectomy accompanied by simultaneous umbilical hernia repair: a retrospective study.

BACKGROUND: Umbilical defects may cause technical problems for general surgeons in patients during laparoscopic cholecystectomy (LC) operations and may increase the incidence of incisional hernia. AIM: The objectives of this study were to determine the optimal repair method for umbilical hernias that already exist or are encountered incidentally and to present data regarding potential problems that may occur during LC. SETTINGS AND DESIGN: Medical records of patients who had received simultaneous umbilical hernia repair (UHR) with LC were investigated retrospectively. MATERIALS AND METHODS: Cholelithiasis was accompanied by umbilical hernia in 64 (8.6%) out of 745 patients who underwent LC and UHR simultaneously in our hospital between 2000 and 2004. STATISTICAL ANALYSIS USED: The Mann-Whitney U, Chi-square, One-Way Anova, Kaplan-Meier survival analysis, the log-rank test and t test were used for statistical analyses. RESULTS: LC was followed by UHR using primary suture (Group 1), Mayo repair (Group 2) and flat mesh-based repair (Group 3) in 32 (50%), 18 (28.1%) and 14 (21.9%) patients, respectively. Mean body mass indexes (BMI) of patients were 26.6 kg/m 2, 29.2 kg/m 2 and 39.9 kg/m 2 in Groups 1, 2 and 3, respectively. Recurrence rates were 9.4%, 5.6% and none (0%) in Groups 1, 2 and 3, respectively. Recurrence was observed in three (7.0%) out of 43(67.2%) patients with BMI > or = 30 kg/m 2 while umbilical hernia recurred in one (4.8%) out of 21 (32.8%) patients with BMI < 30 kg/m 2. Overall morbidity and mortality rates were 14.1% and 0%, respectively. CONCLUSIONS: The outcomes of the UHR with mesh after laparoscopic surgeries appear to be better for either obese or non-obese patients than primary suture techniques in recurrence rates.

Modified experimental mild traumatic brain injury model.

BACKGROUND: Experimental models of traumatic brain injury (TBI), using a variety of techniques and species, have been devised with the aim of producing repeatable lesions resembling those found in head injuries. There are various TBI models mentioned in the literature. In experimental head trauma models, emphasis has been placed on the severe head injuries. There are only a few models developed to study mild traumatic brain injury (MTBI). In fact, MTBI is as important a problem as severe head injuries for neurosurgeons. METHODS: Fifty-six male Sprague-Dawley rats were subjected to MTBI with a weight-drop device, which was described by Marmarou et al. The said model was used in its original form as well as in modified forms by employing different weights dropped from the same height. Animals were divided into four groups of 14 rats as follows: Group I (n=14), head injury was induced using 450 g-1 m weight-height impact; Group II (n=14), head injury was induced using 350 g-l m weight-height impact; Group III (n=14), head injury was induced using 300 g-1 m weight-height impact; Group IV (n=14), control group, no injury was applied. Animals were evaluated neurologically, physiologically, electrophysiologically, and histopathologically. RESULTS: Group I and II animals (450 and 350 g-1m weight-height impact, respectively) showed the symptoms of severe head injury, whereas Group III animals (300 g-l m) showed more MTBI symptoms. CONCLUSION: We recommend the application of the modified MTBI model used for group III (300 g-l m weight-height impact) as the most appropriate and the simplest model for future MTBI studies.

The effects of environmental light--dark changes on experimental mild traumatic brain injury.

OBJECTIVES: The aim of this study was to investigate the effects of environmental light-dark changes on the outcome of mild traumatic brain injury (MTBI) using an experimental rodent model. The functions of endogenous and exogenous melatonin on the outcome of injury were also investigated METHODS: Mild traumatic brain injury was experimentally induced in 56 male Sprague-Dawley rats using a weight-drop device. Animals were divided into four groups of 14 each as follows: (i) sham-operated (trauma only, normal day-night cycle), (ii) treated with melatonin (trauma+melatonin, normal day-night cycle), (iii) darkness-induced (trauma+48 h constant dark), and (iv) treated with melatonin and darkness-induced (trauma+48 h constant dark+melatonin). Melatonin (50 mg/kg) was administered, intraperitoneally, immediately after trauma. EEG recordings were taken at three time periods (pretrauma, immediately after trauma, and 48 h after trauma). Motor functions were tested pretrauma, 24 and 48 h post-trauma. Serum melatonin levels were determined pretrauma and 48 h post-trauma. Tissue samples from right frontal area were taken 48 h after trauma for light and electron microscopic examinations. CONCLUSION: Following MTBI light deprivation alone and light deprivation in combination with exogenously administered melatonin indicated significant neuroprotective effects. Although there may be other important pathways, darkness-induced elevation in endogenous melatonin secretion appears to play an important role in this neuroprotective outcome.

The effects of citicoline and lamotrigine alone and in combination following permanent middle cerebral artery occlusion in rats.

The neuroprotective efficacies of citicoline and lamotrigine, alone and in combination, were investigated in experimental permanent focal ischemia. Seven groups of adult male rats underwent focal cerebral ischemia and were given the following treatments: placebo (P), low and high doses of citicoline (C250 and C500, 250 and 500 mg/kg/day i.p., respectively), low and high doses of lamotrigine (L50 and L100, 50 and 100 mg/kg/day p.o., respectively), and combination regimes of both drugs in low (C250 + L50) and high doses (C500 + L100). Citicoline, but not lamotrigine, exerted neuroprotective efficacy during this acute ischemic stroke model. The citicoline and lamotrigine combination did not provide a significant additive neuroprotective effect.

The effect of skin transplantation on tumor growth in mice.

BACKGROUND: Skin allograft is an immunostimulant. Skin allograft activates effector arms of the immune system including the cytotoxic T lymphocytes, activated macrophages, and natural killer cells. These cells may be involved in the destruction of tumor cells. METHODS: Balb/c mice were divided into the study (n = 10) and control (n = 10) groups. Alloskin grafts 1 cm in diameter from the backs of Swiss albino mice were placed on the backs of balb/c mice (study group). The same size autoskin grafts from the backs of other balb/c mice were used for the control group. Fourteen days after grafting, we inoculated 1,000 Ehrlich ascites tumor cells intraperitoneally into both groups. Two days after tumor inoculation, we used secondary allografts and autografts (which were about 2 to 3 mm in diameter) for the same groups. We followed up graft survival and animal survival in both groups. RESULTS: All 10 of the autografted mice died between the 18th and 25th days owing to malignancy. In the allografted group, 2 mice died (1 on day 17 and the other on day 23). Allograft rejection had not occurred in these 2 mice at the time of their death. The other 8 mice in the same group rejected allograft, on average within 9 days (9+/-3, median 8). These 8 mice were alive and without apparent health problems during the 4 months of follow-up. CONCLUSION: Allo-skin graft rejection may help rejection of tumor cells and may be of use in immunotherapy of cancer.

Brainstem auditory and visual evoked potentials in children with protein-energy malnutrition.

BACKGROUND: To determine the effects of malnutrition on the developing brain with brainstem auditory evoked potentials (BAEP) and flash visual evoked potentials (fVEP). METHODS: The BAEP and fVEP of 11 kwashiorkor (8 +/- 1.56 months) and 10 marasmus (7.9 +/- 1.27 months) patients and 10 healthy control subjects (7.65 +/- 0.82 months) were recorded and the measurements were compared with each other in relation with plasma total protein and albumin levels. RESULTS: There were no differences between the mean latencies of the waves I, II, III and IV and mean interpeak latencies (IPL) of the waves I-III of the BAEP and the wave IV (N2) of the fVEP between the three groups. Mean latency of the wave V and mean IPL of the waves I-V and the waves III-V were significantly different between the three groups. The kwashiorkor group had significantly longer mean latency of the wave V than the marasmus group on the right ear and the control group on the both of the ears. The kwashiorkor group had significantly longer mean IPL of the waves I-V than the marasmus group on the right ear and than the control group on the left ear. The kwashiorkor group had also significantly longer mean IPL of the waves III-V than the control group on the left. CONCLUSIONS: The BAEP and fVEP are non-invasive electrophysiologic methods reflecting the integrity or disruption of the central neurologic pathways. The present results confirm the disruption of the central nervous system with the BAEP in children with protein-energy malnutrition, especially in kwashiorkor patients.

Synergistic effects of citicoline and MK-801 in temporary experimental focal ischemia in rats.

BACKGROUND AND PURPOSE: Citicoline, a naturally occurring precursor of phosphatidylcholine, is neuroprotective and is currently being assessed in clinical trials. To evaluate potential synergistic neuroprotective effects of prolonged citicoline treatment and early N-methyl-D-aspartate (NMDA) antagonist therapy, suboptimal treatment regimens of citicoline and MK-801 were tested alone and in combination in a rat model of temporary focal ischemia. METHODS: Four groups of Sprague-Dawley rats (n = 12 per group) underwent 90 minutes of temporary middle cerebral artery occlusion (MCAO) with the suture model. Animals were randomly and blindly assigned to one of four treatment groups: (1) saline, vehicle; (2) MK-801, 0.5 mg/kg IV bolus at 60 minutes after MCAO followed by saline 1 mL/kg IP daily for 7 days; (3) saline IV at 60 minutes after MCAO followed by citicoline 250 mg/kg IP daily for 7 days; or (4) both MK-801 and citicoline (daily for 7 days) active treatment. Triphenyltetrazolium chloride staining was used to assess postmortem infarct volume. Neurological scores were determined daily. RESULTS: Premature mortality between days 2 and 4 was 33.3% in group 1, 41.7% in groups 2 and 3, and 25.0% in group 4. Mean corrected infarct volume was significantly reduced in group 4 compared with the others (175.2 +/- 89.3 mm3 in group 1, 179.1 +/- 78.5 mm3 in group 2, 163.9 +/- 73.7 mm3 in group 3, and 84.7 +/- 56.8 mm3 in group 4 [P < .02, ANOVA and P < .05, Scheffé's test for group 1 versus group 4]). Mean infarct volume in animals dying prematurely was significantly (P < .05, Student's t test) larger in group 1 than those surviving for 7 days (247.2 +/- 89.5 versus 139.2 +/- 68.2 mm3), but there was no significant difference in infarct volume in groups 2, 3, and 4 between animals dying prematurely and those surviving for 7 days. CONCLUSIONS: These results demonstrate synergistic neuroprotective effects of citicoline and an NMDA antagonist in temporary experimental focal ischemia.