Variations of perforating arteries of anterior communicating artery in cases with anterior communicating artery aneurysms: a cadaveric anatomical study.

PURPOSE: In terms of postoperative morbidity and mortality, preservation of the perforating arteries branching from the anterior communicating artery (ACoA) during clipping is particularly imperative in patients with ACoA aneurysm. In the present study, we aimed to investigate whether perforating arteries originated from ACoA were pushed away in a different location in patients with ACoA aneurysm. Furthermore, if they did so, we aimed to identify the direction in which they were dislocated and how the perforating arteries could be preserved during clipping. METHODS: Herein, we categorized 40 brains obtained from cadavers into two groups. The first (n = 26) and second (n = 14) groups included cases without and with ACoA aneurysms, respectively. After completing the preparation procedure, the brains were dissected using surgical microscope and the relevant anatomical region was examined and photographed. Finally, statistical analyses were performed on the data and the results were documented. RESULTS: In the aneurysms with posterior and superior projections, the perforators appeared to be pushed away inferiorly and were frequently noted at the anteroinferior part of the aneurysm neck. Most of the cases, where one of the A1s was larger at one side, the perforating arteries arose from the larger A1 side. CONCLUSION: The mortality and morbidity associated with damage to the perforators can be reduced by approaching the patient from the dominant A1 side and pursuing the perforators primarily at the anteroinferior part of the aneurysm neck in the aneurysms with superior and posterior projections.

NEAT1 Is a Novel Oncogenic LncRNA and Correlated with miR-143 in Pediatric Oligodendrogliomas.

INTRODUCTION: The noncoding RNAs (ncRNAs) play a role in biological processes of various cancers including gliomas. The majority of these transcripts are uniquely expressed in differentiated tissues or specific glioma types. Pediatric oligodendroglioma (POG) is a rare subtype of diffuse glioma and accounts for <1% of pediatric brain tumors. Because histologically POG resembles adult OG, the same treatment is applied as adults. However, the significance in predicting outcomes in POG patients is unclear. In this study, we aimed to investigate the prognostic significance of expression -profiles of microRNA (miRNA) and long noncoding RNA -(LncRNA) in POGs. METHODS: We investigated the levels of 13 known miRNAs and 6 LncRNAs in tumor samples from 9 patients with primary POG by using RT-PCR and analyzed their association with outcomes. RESULTS: The expression levels of miR-21, miR-106a, miR-10b, and LncRNA NEAT1 were higher, and the expression level of miR-143 was lower in POG tissues compared with normal brain tissues (p = 0.006, p = 0.032, p = 0.034, p = 0.002, and p = 0.001, respectively). High levels of NEAT1 and low expression of miR-143 were associated with decreased probability of short disease-free survival (p = 0.018 and p = 0.022, respectively). DISCUSSION: NEAT1 and miR-143 levels could serve as reciprocal prognostic predictors of disease progression in patients with POG. New treatment models to regulate the expression levels of NEAT1 and miR-143 will bring a new approach to the therapy of POG.

Olea europaea Leaf Extract Improves the Efficacy of Temozolomide Therapy by Inducing MGMT Methylation and Reducing P53 Expression in Glioblastoma.

Unmethylated O6-methylguanine-DNA-methyltransferase (MGMT) promoter leads to Temozolomide (TMZ) resistance in most of the glioblastoma multiforme (GBM) patients. We previously investigated the synergistic effect of Olea europaea leaf extract (OLE) on TMZ cytotoxicity through modulating microRNA expression. To date, knowledge about the effect of OLE on MGMT methylation is insufficient. The aim of the current study was to evaluate the potential modulating effect of OLE on the TMZ response of GBM tumors through MGMT methylation. Exposure to 1 mg/mL OLE caused a significant induction of CpG island methylation in the MGMT gene using Methyl quantitative PCR assay (P < 0.001). In WST-1 analysis, the use of 350 µM TMZ plus 1 mg/mL OLE significantly increased the TMZ response of MGMT unmethylated cells (P = 0.003). Using the comet assay, the impact of 1 mg/mL OLE plus 350 µM TMZ on the formation of DNA strand breaks was significantly higher than that of 450 µM TMZ alone (P < 0.001) and Western blot analysis revealed that, when cells are treated with 1-mg/mL OLE, the total p53 protein levels tended to decrease. The results presented in this study uniquely demonstrated that OLE synergistically increased the TMZ response of GBM tumors by regulating MGMT gene methylation and p53 expression. However, further studies to validate our findings are required.

Investigation of topographical anatomy of Broca's area: an anatomic cadaveric study.

PURPOSE: The sulci constituting the structure of the pars triangularis and opercularis, considered as 'Broca's area', present wide anatomical and morphological variations between different hemispheres. The boundaries are described differently from one another in various studies. The aim of this study was to explore the topographical anatomy, confirm the morphological asymmetry and highlight anatomical variations in Broca's area. METHODS: This study was performed with 100 hemispheres to investigate the presence, continuity, patterns and connections of the sulcal structures that constitute the morphological asymmetry of Broca's area. RESULTS: Considerable individual anatomical and morphological variations between the inferior frontal gyrus and related sulcal structures were detected. Rare bilateralism findings supported the morphological asymmetry. The inferior frontal sulcus was identified as a single segment in 54 % of the right and two separate segments in 52 % of the left hemispheres, which was the most common pattern. The diagonal sulcus was present in 48 % of the right and 54 % of the left hemispheres. It was most frequently connected to the ascending ramus on both sides. A 'V' shape was observed in 42.5 % of the right hemispheres and a 'Y' shape in 38.3 % of the left hemispheres, which was the most common shape of the pars triangularis. Moreover, the full results are specified in detail. CONCLUSIONS: Knowledge of the anatomical variations in this region is indispensable for understanding the functional structure and performing safe surgery. However, most previously published studies have aimed to determine the anatomical asymmetry of the motor speech area without illuminating the topographical anatomy encountered during surgery.

microRNA expression pattern modulates temozolomide response in GBM tumors with cancer stem cells.

Temozolomide (TMZ) is widely used to treat glioblastoma multiforme (GBM). Although the MGMT gene methylation status is postulated to correlate with TMZ response, some patients with a methylated MGMT gene still do not benefit from TMZ therapy. Cancer stem cells (CSCs) may be one of the causes of therapeutic resistance, but the molecular mechanism underlying this resistance is unclear. microRNA (miRNA) deregulation has been recognized as another chemoresistance modulating mechanism. Thus, we aimed to evaluate the miRNA expression patterns associated with chemoresistance that is dependent on the CSC status in GBM tumors to identify therapeutic biomarkers. CSCs were identified in 5 of 20 patients' tumor tissues using magnetic separation. CSC (+) tumors displayed a significant induction of CpG island methylation in the MGMT gene promoter (p = 0.009). Using real-time reverse transcription polymerase chain reaction (qRT-PCR), 9 miRNAs related to GBM (mir-181b, miR-153, miR-137, miR-145, miR-10a, miR-10b, let-7d, miR-9, and miR-455-3p), which are associated with cell cycle and invasion was analyzed in tumor samples. Low miR-181b and high miR-455-3p expression levels were detected (p = 0.053, p = 0.004; respectively) in CSC (+) tumors. Analysis revealed a significant correlation between miR-455-3p expression and Smad2 protein levels as analyzed by immunohistochemistry in CSC (+) tumors (p = 0.002). Thus, miR-455-3p may be involved in TMZ resistance in MGMT methylated CSC (+) GBM patients. Further studies and evaluations are required, but this miRNA may provide novel therapeutic molecular targets for GBM treatment and new directions for the development of anticancer drugs.

Tailoring fenestrated aneurysm clips intraoperatively: Instant solution for a difficult problem.

The anterior communicating artery (AcoA) aneurysms represent the most complex aneurysms of the anterior circulation. For years, surgical challenges including the intricate anatomy and narrow surgical corridor have been overcome using supplementary techniques including extended craniotomies, wide opening of the cisterns, gyrus rectus resection and special clips like fenestrated clips. However, imaginative solutions such as intraoperative clip modification may be inevitable in particular cases for safe clipping. We retrospectively analyzed clinical records of two patients who required clip modification intraoperatively. Case #1 underwent microsurgical clipping of a ruptured, 4-mm AcoA aneurysm. Unfortunately, given the short distance between the two A2s, it was not possible to clip the aneurysm without a compromise to the contralateral A2 with the available shortest 3mm-fenestrated clip. We then used the clip modification technique intraoperatively by shortening the clip tips with mesh-plaque cutter and smoothening the remaining sharp ends using cautery sanding. Eventually, the aneurysm was clipped successfully with the modified-fenestrated clip. Post-clipping imagings confirmed complete occlusion of the aneurysm and patency of parent arteries. Case 2# underwent microsurgical clipping for a ruptured, 1-mm AcoA aneurysm. Like Case 1#, the initial clipping attempt with the available shortest 4mm-fenestrated clip failed given the excessive length of the tips. The patient, thus, required clip modification as described above. The aneurysm was then clipped successfully using the modified-fenestrated clip, protecting bilateral A2s. Post-clipping imagings demonstrated patency of parent arteries with no residual aneurysm filling. Clip modification seems to be an effective option in clipping the AcoA aneurysms when available clips are too long to secure them safely.

Neurosurgery training camp for medical student: experience of the Turkish neurosugery academy and Bursa Uludag University.

Introduction: To highlight the importance of hands-on experiences and mentorship in shaping the future workforce of specialized medical professionals via a Neurosurgery Training Camp. Methods: Responses of the questionnaire regarding the Neurosurgery Training Camp organized by Bursa Uludag University's Faculty of Medicine and the Turkish Neurosurgery Academy were reviewed retrospectively. A one-day program was organized to introduce neurosurgery to medical students. During the camp, the students participated in interactive presentations delivered by faculty members, had lunch together, became acquainted with neurosurgical tools and technologies, and performed interventions. With pre and postworkshop questionnaire, student's expectations and thoughts about camp was evaluated. Results: Forty-one students from 10 medical schools, spanning every year of study, attended the camp. Approximately 39% of the attendees (n = 16) were women and 61% (n = 25) were men. The post-workshop survey results demonstrated that 73% of the students (n = 30) were inclined to pursue a career in neurosurgery after the camp, 21.9% (n = 9) remained undecided, and 4.8% (n = 2) chose not to pursue neurosurgery. Feedback from the post-workshop questionnaire highlighted that all students perceived the camp as beneficial in providing insights into their future careers and aiding in making a decision regarding their career paths. Discussion: The neurosurgical training camp effectively inspired and educated medical students about the discipline of neurosurgery. Furthermore, the camp effectively altered the career aspirations and perceptions of neurosurgery among the participating students.

The artery of Percheron revisited: a cadaveric anatomical study.

BACKGROUND: The artery of Percheron (AOP) is a single thalamoperforating arterial trunk that provides bilateral supply to the paramedian thalami and the rostral midbrain. As this rare anatomical variant artery may be involved in endovascular procedures or encountered surgically during basilar terminus aneurysms, the present study was warranted. METHOD: Thirty-four adult (20 male and 14 female) formalin-fixed cadaveric brains underwent dissection of the 68 posterior cerebral arteries. Observations were made of the presence and the variations of the thalamoperforating arteries as well as the presence of the AOP. FINDINGS: Thalamoperforating arteries arose from the superior or posterior surfaces of the P1 segment at a mean of a 1.87 mm (range, 0.39-5.25 mm) distance from the basilar apex and entered the brain through the posterior perforated substance. The average number was 4.25 (range 1-9), and the mean diameter was 0.73 mm (range 0.46-1.16 mm). Thalamoperforating arteries were classified into four different types according to their origin at the P1 segment: type I (bilateral multiple, n = 19), 55.8 %; type II (unilateral multiple, unilateral single, n = 4), 11.7 %; type III (bilateral single, n = 7), 20.5 %; type IV [one side with a single branch, the other side with no branches (the AOP), n = 4], 11.7 %. In three separate specimens with ruptured basilar artery aneurysms, the origin of the thalamoperforating arteries was incorporated not only into the posterior aspect of the aneurysm neck but also into the fundus. CONCLUSIONS: In about one tenth of cases the possibility of the presence of a single arterial trunk that supplies the two paramedian thalamic territories should be taken into consideration during treatment planning of basilar terminus aneurysms. Furthermore, our data show that the thalamoperforating arteries may take off from both the aneurysm neck and the fundus.

Crystal storing histiocytosis forming a mass lesion in temporal lobe.

Crystal storing histiocytosis is a disorder characterized by local or diffuse infiltration of histiocytes containing crystalline inclusions. This entity has been reported in several organs, however the involvement of the central nervous system (CNS) is extremely rare and to date only 7 cases of crystal storing histiocytosis (CSH) of CNS have been reported in the English literature. More than 90% patients with CSH had an underlying lymphoproliferative or plasma cell disorders, especially multiple myeloma, lymphoplasmacytic lymphoma or monoclonal gammopathy. Radiologically and intraoperatively, CSH may mimic an infectious process or neoplasm, hence its histopathological confirmation is important to facilitate appropriate treatment. In this report, we describe an additional case of crystal storing histiocytosis in a 48 year old female who presented with a mass lesion in the right temporal lobe of the cerebrum.

Diabetes Mellitus-Mediated MALAT1 Expression Induces Glioblastoma Aggressiveness.

AIM: To describe the role of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in glioblastoma (GB) progression in patients concurrently diagnosed with diabetes mellitus (DM). MATERIAL AND METHODS: Formalin-fixed paraffin-embedded (FFPE) tumor samples of 47 patients diagnosed with GB only and 13 patients diagnosed with GB and DM (GB-DM) were enrolled in this study. Data for p53 and Ki67 immunohistochemical staining of the tumors and blood HbA1c levels of patients with DM were retrospectively collected. MALAT1 expression was assessed using quantitative real-time polymerase chain reaction. RESULTS: The coexistence of GB and DM induced the nuclear expression of p53 and Ki67 compared with GB only. MALAT1 expression was higher in GB-DM tumors than in GB only tumors. The expression of MALAT1 and HbA1c levels were positively correlated. Additionally, MALAT1 was positively correlated with tumoral p53 and Ki67. The disease-free survival of patients with GB-DM with high MALAT1 expression was shorter than that of those diagnosed with GB only and with a lower MALAT1 expression. CONCLUSION: Our findings suggest that one of the mechanisms of the facilitating effect of DM on GB tumor aggressiveness is via MALAT1 expression.

Olea europaea Leaf Phenolics Oleuropein, Hydroxytyrosol, Tyrosol, and Rutin Induce Apoptosis and Additionally Affect Temozolomide against Glioblastoma: In Particular, Oleuropein Inhibits Spheroid Growth by Attenuating Stem-like Cell Phenotype.

The effects of Olea europaea leaf extract (OLE) phenolics, including oleuropein (OL), hydroxytyrosol (HT), tyrosol (TYR), and rutin against glioblastoma (GB), independently and in combination with temozolomide (TMZ), were investigated in T98G and A172 cells. Cell growth was assessed by WST-1, real-time cell analysis, colony formation, and cell cycle distribution assays. A dual acridine orange propidium iodide (AO/PI) staining and annexin V assay determined cell viability. A sphere-forming assay, an intracellular oxidative stress assay, and the RNA expression of CD133 and OCT4 investigated the GB stem-like cell (GSC) phenotype. A scratch wound-healing assay evaluated migration capacity. OL was as effective as OLE in terms of apoptosis promotion (p < 0.001) and GSC inhibition (p < 0.001). HT inhibited cell viability, GSC phenotype, and migration rate (p < 0.001), but its anti-GB effect was less than the total effect of OLE alone. Rutin decreased reactive oxygen species production and inhibited colony formation and cell migration (p < 0.001). TYR demonstrated the least effect. The additive effects of OL, HT, TYR and rutin with TMZ were significant (p < 0.001). Our data suggest that OL may represent a novel therapeutic approach against GB cells, while HT and rutin show promise in increasing the efficacy of TMZ therapy.

Co-loading of Temozolomide with Oleuropein or rutin into polylactic acid core-shell nanofiber webs inhibit glioblastoma cell by controlled release.

Glioblastoma (GB) has susceptibility to post-surgical recurrence. Therefore, local treatment methods are required against recurrent GB cells in the post-surgical area. In this study, we developed a nanofiber-based local therapy against GB cells using Oleuropein (OL), and rutin and their combinations with Temozolomide (TMZ). The polylactic acid (PLA) core-shell nanofiber webs were encapsulated with OL (PLAOL), rutin (PLArutin), and TMZ (PLATMZ) by an electrospinning process. A SEM visualized the morphology and the total immersion method determined the release characteristics of PLA webs. Real-time cell tracking analysis for cell growth, dual Acridine Orange/Propidium Iodide staining for cell viability, a scratch wound healing assay for migration capacity, and a sphere formation assay for tumor spheroid aggressiveness were used. All polymeric nanofiber webs had core-shell structures with an average diameter between 133 ± 30.7-139 ± 20.5 nm. All PLA webs promoted apoptotic cell death, suppressed cell migration, and spheres growth (p < 0.0001). PLAOL and PLATMZ suppressed GB cell viability with a controlled release that increased over 120 h, while PLArutin caused rapid cell inhibition (p < 0.0001). Collectively, our findings suggest that core-shell nano-webs could be a novel and effective therapeutic tool for the controlled release of OL and TMZ against recurrent GB cells.

Magnetic resonance spectroscopy findings of pyogenic, tuberculous, and Cryptococcus intracranial abscesses.

Proton magnetic resonance spectroscopy (MRS) complements conventional methods used to differentiate intracranial cystic lesions. We report MRS findings of three cases that were diagnosed as pyogenic, tuberculous, and Cryptococcus abscesses before instituting any medical or surgical therapy. The pyogenic brain abscess had typical specific spectral findings (i.e., the demonstration of amino acids). Lactate and lipid peaks were visible in the tuberculous abscess. Cryptococcus neoformans can appear differently in different brain regions, which may lead to different spectral findings.

Cerebellar granulocytic sarcoma: a case report.

Granulocytic sarcoma is a rare tumor composed of immature granulocytic cells that is usually associated with acute myelogenous leukemia. Intraparenchymal cranial localization without skull, meningeal, or bone marrow invasion is extremely rare. The mechanisms of intraparenchymal cranial localization of GS remains unknown, as only 10 cases with cerebellar granulocytic sarcoma have been previously reported. Herein, we report a four year old boy with cerebellar localization of granulocytic sarcoma.

Long non-coding RNAs as a predictive markers of group 3 medulloblastomas.

ObjectiveThe appropriate treatments for the different molecular subgroups of medulloblastomas are challenging to determine. Hence, this study aimed to examine the expression profiles of long non-coding RNAs (LncRNAs) to determine a marker that may be important for treatment selection in these subgroups.MethodsChanges in the expression of LncRNAs in the tissues of patients with medulloblastoma, which are classified into four subgroups according to their clinical characteristics and gene expression profiles, were examined via reverse transcription polymerase chain reaction. Moreover, there association with patient prognosis was evaluated.ResultsThe expression levels of MALAT1 and SNGH16 were significantly higher in patients with group 3 medulloblastoma than in those with other subtypes. Patients with high expression levels of MALAT1 and SNGH16 had a relatively shorter overall survival than those with low expression levels.ConclusionsPatients with group 3 medulloblastoma have a high MALAT1 level, which is associated with poor prognosis. Therefore, MALAT1 can be a new therapeutic target in medulloblastoma.

Reliability of CT angiography scoring systems used for brain death and the effect of cranial interventions on the results.

OBJECTIVE: To assess vascular opacifications, the efficiency, and interobserver agreement (IOA) of five different computed tomography angiography (CTA) brain death (BD) scoring systems in patients with and without cranial interventions, for determining alternative findings correctly supporting BD diagnosis by CTA even in cranial intervention presence. METHODS: 45 patients clinically identified with BD and evaluated with CTA were included. IOA of five different scoring systems used for CTA BD diagnosis, the effect of intracranial interventions on scoring systems, and vascular opacification were evaluated. RESULTS: IOA was almost perfect (κ = 0.843-0.911, p < 0.05) and substantial (κ = 0.771-0.776, p < 0.05) in all scoring systems. Significant relationships were observed between craniectomy presence and middle cerebral artery M4 segment and internal cerebral vein (ICV) opacification. No opacification was observed in straight sinus (SS) by observers in any of the craniectomized patients. CONCLUSION: IOA of CTA scoring systems is adequate. But a significant degree of false-negative results is observed due to ICV filling in craniectomy cases. Opacification presence in SS can give an idea of BD in these cases.

Coexistence of TERT C228T mutation and MALAT1 dysregulation in primary glioblastoma: new prognostic and therapeutic targets.

Objective: This study was designed to conduct molecular classification based on IDH1/2, TERT, ATRX, and DAXX changes in pediatric and adult primary glioblastoma (GB) and to analyze the potential interaction of LncRNA MALAT1 in the determined homogeneous subgroups.Methods: We analyzed the expression profiles of ATRX/DAXX and MALAT1 using the qRT-PCR method and IDH and TERT mutation status using DNA sequencing analysis in 85 primary pediatric and adult GB patients.Results: IDH1 mutation was observed in 5 (5.88%) and TERT mutation in 65 (76.47%) primary pediatric and adult GB patients. ATRX and DAXX were detected in 18 (21.18%) and 7 (8.24%) patients. TERT mutation and loss of ATRX/DAXX were associated with short overall survival (p < 0.001, p < 0.001, respectively). Patients carrying especially TERT C228T mutation had worse prognosis (p < 0.001). Six subgroups were obtained from the genetic analysis. Among the subgroups, MALAT1 was highly expressed in group A that had a single TERT mutation as compared to that in groups D and E (p = 0.001 and p < 0.001, respectively); further, high MALAT1 expression was associated with worse prognosis in patients with C228T mutation (p < 0.001).Conclusions: Our findings highlight that the presence of TERT C228T mutation and expression of MALAT1 can be used as primary targets during the follow-up of primary GB patients and in the development of new treatment strategies.

Diagnostic value of the CSF levels of D-Lactate and pro-inflammatory cytokines (TNF-alpha, IL-6, IL-8 and IL-17) in the patients with suspected nosocomial meningitis.

INTRODUCTION: This study aims to determine the diagnostic value of IL-6, IL-8, IL-17, TNF-α and D-lactate levels in the cerebrospinal fluid (CSF) in nosocomial meningitis. METHODS: CSF levels of cytokines and D-lactate were compared across 29 episodes who were diagnosed with nosocomial meningitis, 38 episodes with pleocytosis but without meningitis and 54 control subjects. RESULTS: CSF levels of IL-6, IL-8, and D-lactate were higher in the group with nosocomial meningitis compared to the control group and to the group with pleocytosis without meningitis (p<0.05). For the levels of IL-6, when the threshold was considered to be > 440 pg/mL, the sensitivity and specificity were 55.17% and 94.74%, respectively. For IL-8 levels, when the threshold was considered to be >1249 pg/mL, the sensitivity and specificity were 44.83% and 84.21%, respectively. In the patients with nosocomial meningitis, when the threshold of D-lactate levels was considered to be >1.05µmol/mL, the sensitivity and specificity were found to be 75.86% and 63.16%, respectively. In the pleocytosis without meningitis CSF samples and in the CSF samples diagnosed with nosocomial meningitis, the highest AUC was calculated for triple combination model of IL-6, IL-8, and D-lactate levels (AUC= 0.801, p<0.001), and double combination model IL-6 and IL-8 (AUC= 0.790) (p<0.001). CONCLUSION: In our study, we have concluded that IL-6, IL-8 and D-lactate levels could be diagnostic markers for nosocomial meningitis.

Comparison of Clinical and Molecular Wnt and SHH Subgroups in Medulloblastoma Tumor Cases.

AIM: To determine the Wnt and SHH subtypes at the molecular level, and to compare them clinically by examining the changes in CTNNB1, AXIN, PTCH1, SMO, SUFU, and GLI1 mRNA expression in the medulloblastoma of a Turkish population determined according to patient selection criteria. In this context, the clinical distinction between Wnt and SHH groups are realized by considering the age, gender, survival time, location of the lesion, and radiological features of the patients. MATERIAL AND METHODS: Molecular separation was performed by RT-PCR analysis of CTNNB1, AXIN, PTCH1, SMO, SUFU, and GLI1 mRNA expression changes. RESULTS: About 17.8% and 22.2% of the cases were included in the Wnt and the SHH group, respectively. When comparing group differences based on clinical and molecular data, 72.7% and 66.6% of matches were observed in the Wnt and the SHH group, respectively. CONCLUSION: It has been revealed that molecular analysis and grouping of patients with medulloblastoma can provide support for clinically determined subgroups.

Citicoline and postconditioning provides neuroprotection in a rat model of ischemic spinal cord injury.

BACKGROUND: Ischemic spinal cord injury is a chain of events caused by the reduction and/or cessation of spinal cord blood flow, which results in neuronal degeneration and loss. Ischemic postconditioning is defined as a series of intermittent interruptions of blood flow in the early phase of reperfusion and has been shown to reduce the infarct size in cerebral ischemia. Our study aimed to characterize the relationship between the neuronal injury-decreasing effects of citicoline and ischemic postconditioning, which were proven to be effective against the apoptotic process. METHOD: Spinal cord ischemia was produced in rats using an intrathoracic approach to implement the synchronous arcus aorta and subclavian artery clipping method. In our study, 42 male Sprague-Dawley rats (309 +/- 27 g) were used. Animals were divided into sham operated, spinal ischemia, citicoline, postconditioning, and postconditioning citicoline groups. Postconditioning was generated by six cycles of 1 min occlusion/5 min reperfusion. A 600 mmol/kg dose of citicoline was given intraperitoneally before ischemia in the citicoline and postconditioning citicoline groups. All rats were sacrificed 96 h after reperfusion. For immunohistochemical analysis, bcl-2, caspase 3, caspase 9, and bax immune staining were performed. Caspase 3, caspase 9, bax, and bcl-2 were used as apoptotic and antiapoptotic markers, respectively. FINDINGS: The blood pressure values obtained at the onset of reperfusion were significantly lower than the preischemic values. A difference in immunohistochemical scoring was detected between the caspase 3, caspase 9, bax, and bcl-2 groups. When comparisons between the ischemia (groups 2, 3, 4, and 5) and sham groups (group 1) were performed, a significant increase in caspase 3, caspase 9, bax, and bcl-2 was detected. When comparing the subgroups, the average score of caspase 9 was found to be significantly higher in ischemia group 2. The average score of bcl-2 was also found to be significantly higher in postconditioning and citicoline group 5. CONCLUSIONS: It is thus thought that combining citicoline with postconditioning provides protection by inhibiting the caspase pathway and by increasing the antiapoptotic proteins.