Systematic Analysis of Metabolic Bottlenecks in the Methylerythritol 4-Phosphate (MEP) Pathway of Zymomonas mobilis.

Zymomonas mobilis is an industrially relevant aerotolerant anaerobic bacterium that can convert up to 96% of consumed glucose to ethanol. This highly catabolic metabolism could be leveraged to produce isoprenoid-based bioproducts via the methylerythritol 4-phosphate (MEP) pathway, but we currently have limited knowledge concerning the metabolic constraints of this pathway in Z. mobilis. Here, we performed an initial investigation of the metabolic bottlenecks within the MEP pathway of Z. mobilis using enzyme overexpression strains and quantitative metabolomics. Our analysis revealed that 1-deoxy-d-xylulose 5-phosphate synthase (DXS) represents the first enzymatic bottleneck in the Z. mobilis MEP pathway. DXS overexpression triggered large increases in the intracellular levels of the first five MEP pathway intermediates, of which the buildup in 2-C-methyl-d-erythritol 2,4-cyclodiphosphate (MEcDP) was the most substantial. The combined overexpression of DXS, 4-hydroxy-3-methylbut-2-enyl diphosphate (HMBDP) synthase (IspG), and HMBDP reductase (IspH) mitigated the bottleneck at MEcDP and mobilized carbon to downstream MEP pathway intermediates, indicating that IspG and IspH activity become the primary pathway constraints during DXS overexpression. Finally, we overexpressed DXS with other native MEP enzymes and a heterologous isoprene synthase and showed that isoprene can be used as a carbon sink in the Z. mobilis MEP pathway. By revealing key bottlenecks within the MEP pathway of Z. mobilis, this study will aid future engineering efforts aimed at developing this bacterium for industrial isoprenoid production. IMPORTANCE Engineered microorganisms have the potential to convert renewable substrates into biofuels and valuable bioproducts, which offers an environmentally sustainable alternative to fossil-fuel-derived products. Isoprenoids are a diverse class of biologically derived compounds that have commercial applications as various commodity chemicals, including biofuels and biofuel precursor molecules. Thus, isoprenoids represent a desirable target for large-scale microbial generation. However, our ability to engineer microbes for the industrial production of isoprenoid-derived bioproducts is limited by an incomplete understanding of the bottlenecks in the biosynthetic pathway responsible for isoprenoid precursor generation. In this study, we combined genetic engineering with quantitative analyses of metabolism to examine the capabilities and constraints of the isoprenoid biosynthetic pathway in the industrially relevant microbe Zymomonas mobilis. Our integrated and systematic approach identified multiple enzymes whose overexpression in Z. mobilis results in an increased production of isoprenoid precursor molecules and mitigation of metabolic bottlenecks.

Rapid Targeted Quantitation of Protein Overexpression with Direct Infusion Shotgun Proteome Analysis (DISPA-PRM).

While much effort has been placed on comprehensive quantitative proteome analysis, certain applications demand the measurement of only a few target proteins from complex systems. Traditional approaches to targeted proteomics rely on nanoliquid chromatography (nLC) and targeted mass spectrometry (MS) methods, e.g., parallel reaction monitoring (PRM). However, the time requirement for nLC can limit the throughput of targeted proteomics. To achieve rapid and high-throughput targeted methods, here we show that nLC separations can be eliminated and replaced with direct infusion shotgun proteome analysis (DISPA) using high-field asymmetric waveform ion mobility spectrometry (FAIMS) with PRM. We demonstrate the application of DISPA-PRM for rapid targeted quantification of bacterial enzymes utilized in the production of biofuels by monitoring temporal expression in 72 metabolically engineered bacterial cultures in less than 2.5 h, with a measured dynamic range >1200-fold. We conclude that DISPA-PRM presents a valuable innovative tool with results comparable to nLC-MS/MS, enabling fast and rapid detection of targeted proteins in complex mixtures.

Metabolic Remodeling during Nitrogen Fixation in Zymomonas mobilis.

Zymomonas mobilis is an ethanologenic bacterium currently being developed for production of advanced biofuels. Recent studies have shown that Z. mobilis can fix dinitrogen gas (N2) as a sole nitrogen source. During N2 fixation, Z. mobilis exhibits increased biomass-specific rates of ethanol production. In order to better understand the physiology of Z. mobilis during N2 fixation and during changes in ammonium (NH4+) availability, we performed liquid chromatography-mass spectrometry (LC-MS)-based targeted metabolomics and shotgun proteomics under three regimes of nitrogen availability: continuous N2 fixation, gradual NH4+ depletion, and acute NH4+ addition to N2-fixing cells. We report dynamic changes in abundance of proteins and metabolites related to nitrogen fixation, motility, ammonium assimilation, amino acid biosynthesis, nucleotide biosynthesis, isoprenoid biosynthesis, and Entner-Doudoroff (ED) glycolysis, providing insight into the regulatory mechanisms that control these processes in Z. mobilis. Our analysis identified potential physiological mechanisms that may contribute to increased specific ethanol production during N2 fixation, including decreased activity of biosynthetic pathways, increased protein abundance of alcohol dehydrogenase (ADHI), and increased thermodynamic favorability of the ED pathway. Of particular relevance to advanced biofuel production, we found that intermediates in the methylerythritol phosphate (MEP) pathway for isoprenoid biosynthesis were depleted during N2 fixation, coinciding with decreased protein abundance of deoxyxylulose 5-phosphate synthase (DXS), the first enzyme in the pathway. This implies that DXS protein abundance serves as a native control point in regulating MEP pathway activity in Z. mobilis. The results of this study will inform metabolic engineering to further develop Z. mobilis as a platform organism for biofuel production. IMPORTANCE Biofuels and bioproducts have the potential to serve as environmentally sustainable replacements for petroleum-derived fuels and commodity molecules. Advanced fuels such as higher alcohols and isoprenoids are more suitable gasoline replacements than bioethanol. Developing microbial systems to generate advanced biofuels requires metabolic engineering to reroute carbon away from ethanol and other native products and toward desired pathways, such as the MEP pathway for isoprenoid biosynthesis. However, rational engineering of microbial metabolism relies on understanding metabolic control points, in terms of both enzyme activity and thermodynamic favorability. In Z. mobilis, the factors that control glycolytic rates, ethanol production, and isoprenoid production are still not fully understood. In this study, we performed metabolomic, proteomic, and thermodynamic analysis of Z. mobilis during N2 fixation. This analysis identified key changes in metabolite levels, enzyme abundance, and glycolytic thermodynamic favorability that occurred during changes in NH4+ availability, helping to inform future efforts in metabolic engineering.

A novel hemostatic scaffold material and the importance of scaffold formation on ending hemorrhage: An experimental rat study.

BACKGROUND: Different pharmacological agents are developed to control bleeding. However, it is critical for these agents to induce thrombin formation and have an effect on vasoconstriction, coagulation, and scaffold. In this study, we aimed to demonstrate the agents' ability to stop bleeding properties on minor and major open bleedings after skin clefts, extracorporal injuries, traumatic cuts, spontaneous or surgical intervention besides scaffold properties. For this purpose, a new and authentic hemostatic agent, processed diatomite (PD) and the most preferred chitosan in the medical area were used to test blood stopping and scaffold effects in a rat femoral bleeding model. The samples were examined by scanning electron microscopy (SEM), and the results on blood stopping were shared. METHODS: The current experimental study was conducted on rats. The effects of hemostatic agents on our femoral bleeding model were determined. In this study, 22 male Wistar albino rats weighing 158-215 g, were used. The rats were assigned randomly to three groups: control group (n=6), chitosan group (n=8), and PD group (n=8). Bleeding time, scaffold formation, weight differences, histopathological effect and scanning electron microscope (SEM) analyses were performed. RESULTS: In our experimental model, weight loss was 5.0±1.3 g for the control group, 2.9±1.1 g for the chitosan group, and 2.7±1.0 g for the PD group, respectively. When weighed before and after the experiment, there was a significant change in weights of rats in chitosan, and PD groups regarding scaffold formation: it was complete for six rats (75%) and weak for two (25%) rats in chitosan group; however, it was complete for seven rats (87.5%) and weak for one (12.5%) rat in the PD group. Scaffold formation was significant for the chitosan and PD groups versus the control group (p=0.002). CONCLUSION: In our study, the scaffold formed by PD exerts appropriate porousness and contributes to fibrin formation and prevent re-bleeding. PD had a strong and significant scaffold effect. The effectiveness of PD to stop bleeding was equal to chitosan. Besides being natural, hemostatic agents should not induce cellular damage. We histopathologically demonstrated that PD was harmless for the natural structure of cells and vessels in the femoral site.

Genome Wide Phosphoproteome Analysis of Zymomonas mobilis Under Anaerobic, Aerobic, and N2-Fixing Conditions.

Protein phosphorylation is a post-translational modification with widespread regulatory roles in both eukaryotes and prokaryotes. Using mass spectrometry, we performed a genome wide investigation of protein phosphorylation in the non-model organism and biofuel producer Zymomonas mobilis under anaerobic, aerobic, and N2-fixing conditions. Our phosphoproteome analysis revealed 125 unique phosphorylated proteins, belonging to major pathways such as glycolysis, TCA cycle, electron transport, nitrogen metabolism, and protein synthesis. Quantitative analysis revealed significant and widespread changes in protein phosphorylation across growth conditions. For example, we observed increased phosphorylation of nearly all glycolytic enzymes and a large fraction of ribosomal proteins during aerobic and N2-fixing conditions. We also observed substantial changes in the phosphorylation status of enzymes and regulatory proteins involved in nitrogen fixation and ammonia assimilation during N2-fixing conditions, including nitrogenase, the Rnf electron transport complex, the transcription factor NifA, GS-GOGAT cycle enzymes, and the P II regulatory protein. This suggested that protein phosphorylation may play an important role at regulating all aspects of nitrogen metabolism in Z. mobilis. This study provides new knowledge regarding the specific pathways and cellular processes that may be regulated by protein phosphorylation in this important industrial organism and provides a useful road map for future experiments that investigate the physiological role of specific phosphorylation events in Z. mobilis.

Physical abuse of the elderly: a 4-year retrospective evaluation in the emergency department.

AIM: Elderly physical abuse (EPA) is defined as injury or assault to or the restriction of an elderly person. Although EPA is an important social problem, its diagnosis is difficult because of tendency to cover up the event. In this study, patients aged 65 years and over who presented at the emergency department (ED) for forensic reasons and in whom physical abuse was suspected were examined. The aim of this study was to raise ED awareness of EPA and thereby to contribute to treatment plans for these patients in the ED. METHODS: The study was conducted over a 4-year period between January 2013 and January 2017. Patients were selected retrospectively from the hospital information system according to the following criteria: (i) admission to ED with trauma; (ii) aged 65 and older; and (iii) evaluated as having forensic trauma by an ED specialist based on either the patient's history or the specialist's observations and suspicions. RESULTS: The patients included 80 men (69%) and 36 women (31%), with a mean age of 73.92 ± 7.08 years. The length of ED stay was 0-1 h in 27.6% of patients and 1-6 h in 46.6%. When the causes of physical trauma were examined, general assault was seen as the most prevalent, occurring in nearly 63% of the patients. CONCLUSIONS: There may be three conclusions for the current study: First, although EPA is a rare problem for patients referred to emergency services, health professionals should be suspicious when examining patients 65 years or older because of the difficulties of diagnosing EPA. Second, in patients with no history of suspicious trauma or suspicious radiological imaging results, EPA is also common. Third, because of the undetected EPA mechanism, patients should be examined forensically in suspicious cases and deaths.

Methemoglobinemia treated with hyperbaric oxygen therapy: A case report.

Methemoglobinemia is a rare but clinically important condition that should be considered among differential diagnosis' in cyanosis. The conventional treatments of methemoglobinemia are high flow oxygen and methylene blue therapies. We present a 52-year-old male patient who admitted to emergency room with severe cyanosis and dyspnea after he was exposed to paint thinner and zinc phosphate solution. The patient was diagnosed with methemoglobinemia with a MetHb level of 49.1mm/Hg in his arterial blood gas test. Patient's symptoms and increased MetHb levels were resistant to high flow oxygen and methylene blue therapies so hyperbaric oxygen therapy (HBO) as an alternative treatment was initiated and the patient was cured promptly. In this case presentation, we aim to discuss the alternative treatment modalities in methemoglobinemia patients with persistent hypoxia and cyanosis, who are unresponsive to standard methylene blue treatment.

Serum and Tissue HIF-2 Alpha Expression in CIN, N-Acetyl Cysteine, and Sildenafil-Treated Rat Models: An Experimental Study.

Background and Objectives: Contrast-induced nephropathy (CIN), is acute renal damage due to contrast agents. This study is conducted to evaluate serum and renal heterodimeric nuclear transcription factor (HIF)-2 alpha levels and its tissue expression in contrast-induced nephropathy, and in N-acetyl cysteine (NAC)-and Sildenafil-treated rat models. Materials/Methods: This randomized, controlled, interventional animal study was conducted on Wistar rats. Rats (n = 36) were randomly assigned to four groups: control (n = 9), CIN group (n = 9), CIN + NAC group (n = 9), and sildenafil (n = 9). The rat model was used to form iohexol-originated CIN. During the modeling, prophylactic treatment was performed at the 24th and 48th h. After 48 h of modeling, blood, urine, and tissue samples were obtained for biochemical analyses. HIF-2-α levels were measured in renal tissue, serum, and urine samples. Renal sections were also performed for histopathologic and immunohistochemical evaluations of renal injury and HIF-2-α expression. Results: In the CIN model, HIF-2α levels and other biochemical parameters were significantly increased (p < 0.01). Both sildenafil and NAC efficiently decreased renal damage due to contrast agents, as shown in histopathologic examinations (p < 0.05). Similarly, after treatment with sildenafil and NAC, HIF-2α levels were significantly decreased (p < 0.05). Conclusions: The current study shows that serum and tissue HIF-2α levels decrease in CIN. Besides, the levels and tissue expression of HIF-2α decrease with both NAC and sildenafil treatments. With further studies, HIF-2α can be investigated as a biomarker of CIN and can be used in the follow-up of patients with CIN.

Isolation and Characterization of Cyclic C33 Botryococcenes and a Trimethylsqualene Isomer from Botryococcus braunii Race B.

Three cyclic C33 botryococcenes and one new trimethylsqualene isomer were isolated from the B race, Showa (Berkeley) strain of Botryococcus braunii, which is known to produce large amounts of isoprenoid hydrocarbons ranging in carbon number from 30 to 34. Their purity was determined by GC-MS, and structures were characterized by 1D and 2D NMR. One of these molecules, cyclic C33-1 botryococcene (5), has an unusual connection of a methylenecyclohexane ring to the molecule backbone not seen before in botryococcenes. This report further adds to our knowledge of the wide range of isoprenoid hydrocarbon structures produced by B. braunii.

High-throughput droplet microfluidics screening platform for selecting fast-growing and high lipid-producing microalgae from a mutant library.

Biofuels derived from microalgal lipids have demonstrated a promising potential as future renewable bioenergy. However, the production costs for microalgae-based biofuels are not economically competitive, and one strategy to overcome this limitation is to develop better-performing microalgal strains that have faster growth and higher lipid content through genetic screening and metabolic engineering. In this work, we present a high-throughput droplet microfluidics-based screening platform capable of analyzing growth and lipid content in populations derived from single cells of a randomly mutated microalgal library to identify and sort variants that exhibit the desired traits such as higher growth rate and increased lipid content. By encapsulating single cells into water-in-oil emulsion droplets, each variant was separately cultured inside an individual droplet that functioned as an independent bioreactor. In conjunction with an on-chip fluorescent lipid staining process within droplets, microalgal growth and lipid content were characterized by measuring chlorophyll and BODIPY fluorescence intensities through an integrated optical detection system in a flow-through manner. Droplets containing cells with higher growth and lipid content were selectively retrieved and further analyzed off-chip. The growth and lipid content screening capabilities of the developed platform were successfully demonstrated by first carrying out proof-of-concept screening using known Chlamydomonas reinhardtii mutants. The platform was then utilized to screen an ethyl methanesulfonate (EMS)-mutated C. reinhardtii population, where eight potential mutants showing faster growth and higher lipid content were selected from 200,000 examined samples, demonstrating the capability of the platform as a high-throughput screening tool for microalgal biofuel development.

Trigeminal neuropathic pain following honeybee sting: a case report.

The neurological complications of bee venom poisoning vary from optic neuritis to pontine hematoma. However, to our best knowledge, trigeminal neuropathic pain secondary to bee sting has not been reported previously in the literature. We report the case of a 52-year-old male patient with right-sided trigeminal neuropathic pain that began a month earlier, following a honeybee sting to the right forehead. The patient was successfully treated by CT-guided percutaneous trigeminal tractotomy. The present report demonstrated that a honeybee sting may result in trigeminal neuropathic pain and CT-guided percutaneous trigeminal tractotomy is effective in the treatment of such cases.

[Falls from height in childhood in Diyarbakir province: a questionnaire study combined with clinical data]. / Diyarbakir'da çocukluk çaginda damdan düsmeler: Klinik çalisma ile desteklenmis bir anket çalismasi.

BACKGROUND: In Diyarbakir, the rate of falls from height increases during summer months since people sleep on the unprotected balconies and roofs of their houses. We aimed to determine the frequency of falls from height and the related risk factors. METHODS: We used questionnaire method and clinical data in this study. The questionnaire was administered in 1445 residences. Clinical data were obtained from files of patients hospitalized due to trauma in the Neurosurgery Clinic of Dicle University over the last six years. RESULTS: In this questionnaire study, it was determined that 246 people had fallen, their average age was 15.4 years, 98% of them had fallen accidentally (mostly from 3.6 m height in summer months), mortality was 6.9%, and the prevalence of falls from height over the previous six years was 472/100,000. Of 464 patients who were hospitalized during the last six years, 326 were cases of fall from height and 59% of these patients were falls from a roof. The average age of these patients was 8.9 years, and average height of the fall was 4.2 m. CONCLUSION: Falls from height, particularly from roofs in Diyarbakir, remain a serious problem in terms of public health.

Pituitary carcinoma presenting with multiple metastases: case report.

Pituitary carcinoma, an uncommon tumor in adults, generally presents with craniospinal and systemic metastases. We report a case of pituitary carcinoma with multiple craniospinal metastases in a child. A 9-year-old girl, who had had a ventriculoperitoneal shunt operation 3 years ago, presented with complaints of progressive visual disturbance, headache, speech difficulty, and gait disturbance for the past 2 months. Neurological examination revealed papilledema, visual loss, and dysarthria. Cranial magnetic resonance imaging revealed a large contrast-enhanced tumor in the left frontal region together with multiple lesions in the sellar-parasellar region and posterior fossa. Multiple intraspinal contrast-enhanced metastatic lesions were also seen. Histopathological and immunohistochemical examination of the excised left frontal mass revealed pituitary carcinoma. Treatment with cyclic temozolomide was started after the operation, but the patient died after 2 months without response to medical therapy. This is the first pediatric case, to the authors' knowledge, of a pituitary carcinoma with widespread intracranial and intraspinal metastases.

Anatomoradiological landmarks for accuracy of radiofrequency thermorhizotomy in the treatment of trigeminal neuralgia.

OBJECTIVE: The correct positioning of the electrode is of prime importance for effectiveness and selectivity of percutaneous trigeminal radiofrequency thermorhizotomy (RF-TR) for the treatment of trigeminal neuralgia (TN). The aim of our study was to establish some anatomoradiological landmarks for the purpose of accurate placement of the electrode tip in RF-TR. METHODS: Of 1000 patients who underwent RF-TR, 100 were retrospective and randomly selected and divided into study groups according to postoperative hypoesthesia in the trigeminal nerve divisions. The patients' petroclival angle, petroelectrodal angle, electrode tip, and the petroelectrodal angle/petroclival angle ratio were calculated on lateral cranial x-rays. These measurements were then correlated with the topography of hypoesthesia obtained by the RF-TR to define the anatomoradiological x-ray landmarks corresponding to the divisions of the trigeminal root. The postoperative hypoesthesia groups were correlated with their respective preoperative pain topography to check the accuracy of the thermolesion. In addition, the intraoperatively evoked paresthesia responses and the side effects were evaluated. The results were analyzed using a paired-samples Student's t test, the chi test, and one-way analysis of variance, followed by Bonferroni and Tamhane post hoc tests. RESULTS: All study groups were comparable with respect to age, sex, side effects, electrode tip location, side of TN, and values of petroclival angle. The lowest values of petroelectrodal angle/orbitomeatal electrodal angle and petroelectrodal angle/ petroclival angle were detected in patients with V3 TN, whereas the greatest values were in patients who had TN in all branches of the trigeminal nerve. The greatest height of the electrode was in patients who had TN in all branches, whereas the least height was in patients with V3 TN. When the results were compared with each other, the mean differences were found to be statistically significant between V3 TN patients and the other groups with different P values. There was no statistical difference between the postoperative hypoesthesia data and the preoperative pain topography, which demonstrated evidence of the accuracy of the thermolesion in our series. CONCLUSION: Our data suggest that the determination of the presented landmarks allows customization to individual patient anatomy and may help the surgeon achieve a more selective effect with a variety of percutaneous procedures for each branch of the trigeminal root.

Serum neuron-specific enolase as a predictor of short-term outcome and its correlation with Glasgow Coma Scale in traumatic brain injury.

Elevated serum neuron-specific enolase levels are correlated with brain cell damage. Low scores according to Glasgow Coma Scale are also considered as serious poor prognostic factor. The aims of the study were to investigate whether there is a correlation between the two measurements in patients with traumatic brain injury and whether serum neuron-specific enolase levels have potential as a screening test to predict outcome. A total of 169 consecutive patients with traumatic brain injury admitted to our clinic between 2002 and 2005 are included in this study. Those patients, who had any major health problem before trauma, were excluded from the study. However, patients with isolated head injury were included in the study. Serial serum neuron-specific enolase concentrations taken at the first 2, 24, and 48 h after traumatic brain injury were analyzed. A computed tomography was performed on each patient on admission. Their Glasgow Coma Scale scores were recorded serially. The relationship between Glasgow Coma Scale scores and the serum neuron-specific enolase levels were assessed by statistical methods. There was a significant negative correlation between the serum neuron-specific enolase levels and Glasgow Coma Scale scores. The levels of neuron-specific enolase were significantly higher in the patients who died in 30 days after trauma and whose scores were lower than or equal to 8 points in Glasgow Coma Scale. Although there are several serious limitations of the use of neuron-specific enolase as a biomarker in traumatic brain injury (i.e., hypoperfusion, extracranial trauma, bleeding, liver, or kidney damage also increase the level of neuron-specific enolase), its concentrations may be useful as a practical and helpful screening test to identify neurotrauma patients who are at increased risk and may provide supplementary estimation with radiological and clinical findings.

Multifocal Ewing's sarcoma of the brain, calvarium, leptomeninges, spine and other bones in a child.

Ewing's sarcoma (ES) is a malignant osseous neoplasm that mostly affects children and young male adults, and usually presents as a solitary bony lesion. Multifocal ES of the central nervous system is extremely rare, with an incidence ranging from 1.1% to 4.3%. Clinically, ES may mimic osteomyelitis. In this report, we describe the case of an 11-year-old boy who had multiple calvarial, leptomeningeal, spinal and various other bony lesions of ES, which were diagnosed radiologically and histopathologically. To the best of our knowledge, this is the first time that multiple brain, calvarial and spinal lesions of ES in a single patient have been reported in the English-language literature. We discuss possible mechanisms and differential diagnoses for this rare pathology.

Primary cerebral intraventricular hydatid cyst: a case report and review of the literature.

Intracranial hydatid cysts, which are common in certain areas worldwide, almost always develop at an intraparenchymal site. However, the literature on intraventricular hydatid cysts consists of only 6 independent case reports and about 30 cases that are described in large series. We report on a 10-year-old girl who was admitted with an intracranial cyst. She complained of headache of 10 months' duration that had intensified significantly over the 3 weeks immediately before her admission. The results of a neurologic examination showed bilateral papilledema and slight left hemiparesis. Magnetic resonance imaging revealed a right temporo-parieto-occipital cystic lesion that was causing the shifting of the midline structures to the contralateral side. The giant cyst was successfully removed without rupture. The possibility of infection with Echinococcus granulosus should be included in the differential diagnosis of unspecific neurologic symptoms such as a progressively worsening headache, especially in pediatric patients from the geographic areas in which that parasite is endemic.

An experimental Staphylococcus aureus meningitis model for investigating induced leptomeningeal and subpial inflammation in rats: a transmission electron microscopy study.

OBJECTIVE: To evaluate leptomeningeal and subpial inflammatory responses of experimental Staphylococcus aureus bacteriemia following intraperitoneal and intravenous applications and to compare the inflammatory reactions in different regions of central nervous system. MATERIAL AND METHODS: Forty anesthetized rats were divided into four groups equal in number. The rats in group-I were given 1 ml suspension of Staphylococcus aureus intraperitoneally. Group-II was the control group of group I; it was administrated 1 ml 0.9% NaCl in water intraperitoneally. The rats in group-III were given the same amount of bacteria intravenously. Group IV was the control group of the group-III; it was administrated 1 ml 0.9% NaCl solution intravenously. The rats were sacrificed on the 21st day. Inflammatory changes of different regions of the central nervous system were examined under transmission electron microscopy. Statistical analysis was done by using variance analysis, Bonferroni, Tamhane post hoc, Student's t and univariate tests. RESULTS: Thoracic and occipital regions were the most vulnerable zones. Increasing of collagen tissue was the most detected inflammatory change. CONCLUSION: This experimental model can be used for inducing subpial and leptomeningeal inflammations and it may be developed for investigations of pathogenesis of leptomeningitis during systemic infections.