[Long-term results of dental implantation in military personnel]. / Otdalennye rezul'taty dental'noi implantatsii u voennosluzhashchikh.

BACKGROUND: Currently, the use of the dental implantation method for the medical service of the Armed Forces of the Russian Federation is quite new. The method of dental implantation makes it possible to eliminate defects in the dentition of military personnel and other contingents eligible for medical care in military medical institutions of the Ministry of Defense of Russia. OBJECTIVE: The aim of the study is to substantiate the medical effectiveness of the use of dental implantation in military healthcare. MATERIAL AND METHODS: The study was conducted on the basis of the Department of Maxillofacial Surgery and Surgical Dentistry of the Military Medical Academy named after S.M. Kirov. The study is based on the analysis of long-term results of dental implantation according to medical histories and outpatient records. The study was conducted in 3 stages: stage 1 - study of the medical histories of patients who underwent dental implantation; stage 2 - examination of patients with dental implants and analysis of long-term results; stage 3 - a patient questionnaire was conducted to determine the effectiveness of dental implantation. RESULTS: The structure of complications during dental implantation was revealed. Clinical examples of long-term results of prosthetics using dental implants are presented. It has been established that due to the peculiarity of military service and the remoteness of the locations of military units from the military medical organization, it is not always possible to conduct regular medical examinations and examinations of patients. To identify early symptoms of peri-implantitis, which is more often asymptomatic, preventive examinations of military personnel should be carried out 1-2 times a year. CONCLUSION: To increase the service life of an orthopedic structure with installed dental implants, regular preventive examinations of patients to identify pathological processes are important. In favor of implantation, there is a choice for some categories of military personnel. This is especially important for flight and naval personnel, since dentures installed on dental implants are the only way to preserve their professional suitability in the military accounting specialty. The presence of teeth and the absence of removable dentures is an important requirement when performing combat missions.

[Sanation of petrous bone cholesteatoma in the otosurgical practice]. / Sanatsiia kholesteatomy piramidy visochnoi kosti v otokhirurgicheskoi praktike.

The present article reports the clinical cases of the surgical intervention on 20 patients presenting with petrous bone cholesteatoma. We have identified several clinical variants of petrous bone cholesteatoma based on the results of multispiral computed tomography (MSCT) of the temporal bones and categorized them into the following types in accordance with the classification proposed by Moffat-Smith an M. Sanna for this pathological condition: supralabyrinthine (n=8), supralabyrinthine-apical (n=2), infralabyrinthine (n=3), infralabyrinthine-apical (n=5), massive (n=1), and massive - apical (n=1). The surgical sanation of petrous bone cholesteatoma was performed in all the 20 patients in the absence of the pronounced bone destruction in the walls of the temporal bone pyramid and of the subdural expansion of cholesteatoma. In all the cases, the trepanation cavity remained open till its complete epidermization. The follow up period was around 3 years in duration on the average. The post-surgical analysis of the clinical conditions of each of the 20 patients was performed with special reference to the surgical technique applied for the removal of petrous bone cholesteatoma and the final outcome of the radical treatment.

[Intraoperative fluid therapy during esophagectomy followed by repair]. / Intraoperatsionnaia infuzionnaia terapiia pri ézofagéktomii s odnomomentnoi plastikoi pishchevoda.

AIM: To optimize fluid therapy in transhiatal eshophagectomy by using of goal-oriented infusion therapy based on stroke volume variation. MATERIAL AND METHODS: Our trial enrolled 30 patients who underwent transhiatal esophagectomy followed by repair for the period 2011-2014. Patients were divided into 2 groups. The first group (LT) included 16 patients with liberal fluid therapy. The second group (GDT) consisted of 14 patients in whom goal-oriented fluid therapy was performed. Goal-oriented fluid therapy was implemented via stroke volume variation (SVV). RESULTS: Infusion rate was 6.7 ml/kg/h and 11.5 ml/kg/h in the main and control groups, respectively. Morbidity rate was 28.6% (n=4) and 62.5% (n=10) in the main and control groups respectively. Clavien-Dindo IV complications were lung atelectasis (n=2, 14%), pneumonia (n=1, 7%). Hydrothorax required puncture was noted in 1 (7%) case. Acute respiratory failure as complication IVa was in 1 (9%) patient. In the control group complications were registered in 10 (62.5%) patients. Complications I-II degree included lung atelectasis (n=4, 25%), cervical anastomosis failure (n=1, 6%); complications IVa were observed in 8 cases (50%). It was significant respiratory failure with reduced PO2/FiO2<300. Patients of the main group required less time for postoperative mechanical ventilation (120 [90-300] vs. 315 [215-810] min (p=0.02) and ICU-stay (0.83 [0.7-0.8] vs. 1.75 [1.25-2.75] (p=0.0022).

Oral buspirone causes a shift in the dose-response curve between the elevated-plus maze and Vogel conflict tests in Long-Evans rats: relation of brain levels of buspirone and 1-PP to anxiolytic action.

Most studies concerning the effects of oral buspirone in the rat elevated plus-maze (EPM) test, spontaneous motor activity (SMA) test, and Vogel conflict (VC) test have used Sprague-Dawley or Wistar rats. Although it has been documented that the behavior of Long-Evans rats is more sensitive to detection of anxiolytics when compared to the aforementioned strains, the effects of oral buspirone have not been fully characterized in the Long-Evans strain in the EPM and VC tests. Thus, we studied the effects of orally administered buspirone (0.03-10.0 mg/kg) in the EPM, SMA, and VC (0.3-60.0 mg/kg) tests in Long-Evans rats. In a separate experiment, brain and plasma concentrations of buspirone and 1-(2-pyrimidinyl)-piperazine (1-PP) were determined after oral administration of buspirone (0.3 and 10 mg/kg) to relate the behavioral effects of buspirone with brain and plasma concentrations of buspirone and 1-PP. Our results showed that buspirone exhibited an inverted-U-shaped dose-response curve in both the EPM and the VC tests. In the EPM, buspirone produced anxiolytic activity in a low, narrow dose-range (0.03, 0.1, 0.3 mg/kg, p.o.) with maximum efficacy at 0.3 mg/kg, whereas in the VC test, significant anxiolytic activity was observed in a high, narrow dose-range (10, 30 mg/kg, p.o.) with maximum efficacy occurring at 10 mg/kg. In the SMA test, buspirone (10 mg/kg, p.o.) significantly decreased horizontal activity and vertical movements suggestive of sedation. Also, one hour following oral doses of buspirone (0.3 and 10 mg/kg), both buspirone and 1-PP concentrations were higher in brain when compared with those in plasma. Additionally, the concentrations of 1-PP were always higher in brain and in plasma compared with the concentrations of buspirone. Of particular interest is our finding of the shift in the dose-response curve between the EPM and VC tests. This shift in the dose-response curve is discussed in relation to brain levels of buspirone and 1-PP levels and their anxiolytic action.

Different levels of gamma-synuclein mRNA in the cerebral cortex of dominant, neutral and submissive rats selected in the competition test.

Synucleins are small proteins regulating the filamentous network that in turn influences the release of dopamine and glutamate neurotransmitters involved in mood and motivation processes. We have studied the pattern of synuclein expression in animal models for mania and depression. Dominant behavior, as defined in a food competition test with dyads of rats, can serve as a model of mania and submissive behavior as a model of depression. The expression of alpha-, beta- and gamma-synuclein was analyzed in four regions of cortex from dominant, neutral and submissive rats using TaqMan reverse transcription-polymerase chain reaction technology. The expression levels of gamma-synuclein were elevated consistently in all regions of cerebral cortex of dominant rats (P <0.05; 23.5 +/- 1.1, normalized units) in contrast to the submissive rat group (10.3 +/- 1.2). Neutral rats had intermediate cerebral cortex levels of gamma-synuclein expression (15.7 +/- 1.4) that were significantly lower than that in dominant rats (P <0.05). No changes in alpha- or beta-synuclein expression were observed among the groups. These studies indicate that gamma-synuclein levels in the cerebral cortex were differentially associated with dominant and submissive behavior.

Fiber-optic monitoring coupled with confocal microscopy for imaging gene expression in vitro and in vivo.

Detection of fluorescent signals in living cells is a common and powerful technique used to monitor gene expression for multiple biomedical applications. A disadvantage of this approach in vivo, is the limited accessibility for long-term monitoring of the fluorescent signals within organs in living animals. Because of the multiple applications of gene expression monitoring through fluorescent signals, innovative methods for readout are required. We developed a strategy combining gene transfer, fiber-optic or endoscope monitoring, and confocal microscopy for the brain interstitial or cavitary endoscopic visualization of the efficacy of gene delivery and expression in vivo. The approach is also effective in vitro and can be applied to multiple organs in vivo. We show an example of the detection of green fluorescent protein (GFP)-emitted fluorescence following the administration of recombinant GFP-expressing adenovirus or implantation of rat C6 glioblastoma cells infected with the recombinant GFP adenovirus into the rat hippocampus of chronically cannulated rats. The results show that fiber-optic monitoring coupled with confocal microscopy in gene transfer studies is a practical approach that results in a direct, efficient, rapid, and sensitive visualization of fluorescent signals in the brain. This allows for the continuous real-time in vitro or in vivo brain monitoring of gene expression, accurate anatomical localization, multiple experimental manipulations in the same subject or preparation, while no sacrifice of the animal is required to monitor the efficacy of gene transfer and/or expression.

Abnormal patterns of microtubule-associated protein-2 (MAP-2) immunolabeling in neuronal nuclei and Lewy bodies in Parkinson's disease substantia nigra brain tissues.

Parkinson's disease (PD) is a neurodegenerative disorder associated with the appearance of cytoplasmic Lewy bodies (LBs) in dopaminergic neurons of the substantia nigra and the progressive loss of these neurons. Cytoskeleton alterations and associated impairments of neuronal transport may contribute to neuronal death. Microtubule-associated protein-2 (MAP-2), a cytoskeleton protein is localized primarily in neuronal dendrites and is known to stabilize microtubule assembly and mediate their interactions with other neuronal cell components. To determine if alterations in MAP-2 morphology are present in PD neurons, we used single and double immunohistochemical and immunofluorescent techniques to characterize MAP-2 in PD neuronal tissues. We report abnormal MAP-2 immunolabeling in some neurons of the substantia nigra of PD brain tissues, which were not observed in the normal, age-matched, control brain tissues. Furthermore, MAP-2 was co-localized with alpha-synuclein and ubiquitin in cytoplasmic LBs of neurons. Surprisingly, MAP-2 was also found to form fibrous aggregates and crystal-like structures within neuronal nuclei. These PD-associated alterations in MAP-2 morphology and distribution suggest that impaired neuronal transport may contribute to the progression of neuronal loss in the brains of PD patients.

Pro-inflammatory and anti-inflammatory cytokine mRNA induction in the periphery and brain following intraperitoneal administration of bacterial lipopolysaccharide.

Gram-negative bacteria-derived lipopolysaccharide (LPS or endotoxin) is known to play an important role in immune and neurological manifestations during bacterial infections. LPS exerts its effects through cytokines, and peripheral or brain administration of LPS activates cytokine production in the brain. In this study, we investigated cytokine and neuropeptide mRNA profiles in specific brain regions and peripheral organs, as well as serum tumor necrosis factor (TNF)-alpha protein levels, in response to the intraperitoneal administration of LPS. For the first time, the simultaneous analysis of interleukin (IL)-1beta system components (ligand, signaling receptor, receptor accessory proteins, receptor antagonist), TNF-alpha, transforming growth factor (TGF)-beta1, glycoprotein 130 (IL-6 receptor signal transducer), OB protein (leptin) receptor, neuropeptide Y, and pro-opiomelanocortin (opioid peptide precursor) mRNAs was done in samples from specific brain regions in response to peripherally administered LPS. The same brain region/organ sample was assayed for all cytokine mRNA components. Peripherally administered LPS up-regulated pro-inflammatory cytokine (IL-1beta and/or TNF-alpha) mRNAs within the cerebral cortex, cerebellum, hippocampus, spleen, liver, and adipose tissue. LPS also increased plasma levels of TNF-alpha protein. LPS did not up-regulate inhibitory (anti-inflammatory) cytokine (IL-1 receptor antagonist and TGF-beta1) mRNAs in most brain regions (except for IL-1 receptor antagonist in the cerebral cortex and for TGF-beta1 in the hippocampus), while they were increased in the liver, and IL-1 receptor antagonist was up-regulated in the spleen and adipose tissue. Overall, peripherally administered LPS modulated the levels of IL-1beta system components within the brain and periphery, but did not affect the neuropeptide-related components studied. The data suggest specificity of transcriptional changes induced by LPS and that cytokine component up-regulation in specific brain regions is relevant to the neurological and neuropsychiatric manifestations associated with peripheral LPS challenge.

An efficient, reliable and inexpensive device for the rapid homogenization of multiple tissue samples by centrifugation.

Homogenization of tissue samples is a common first step in the majority of current protocols for RNA, DNA, and protein isolation. This report describes a simple device for centrifugation-mediated homogenization of tissue samples. The method presented is applicable to RNA, DNA, and protein isolation, and we show examples where high quality total cell RNA, DNA, and protein were obtained from brain and other tissue samples. The advantages of the approach presented include: (1) a significant reduction in time investment relative to hand-driven or individual motorized-driven pestle homogenization; (2) easy construction of the device from inexpensive parts available in any laboratory; (3) high replicability in the processing; and (4) the capacity for the parallel processing of multiple tissue samples, thus allowing higher efficiency, reliability, and standardization.

Neither acute nor chronic exposure to a naturalistic (predator) stressor influences the interleukin-1beta system, tumor necrosis factor-alpha, transforming growth factor-beta1, and neuropeptide mRNAs in specific brain regions.

Physical (neurogenic) stressors may influence immune functioning and interleukin-1beta (IL-1beta) mRNA levels within several brain regions. The present study assessed the effects of an acute or repeated naturalistic, psychogenic stressor (predator exposure) on brain cytokine and neuropeptide mRNAs. Acute predator (ferret) exposure induced stress-like behavioral effects, including elicitation of a startle response and reduced exploratory behaviors; these responses diminished after 30 sessions. Moreover, acute and repeated predator exposure, like acute restraint stress, increased plasma corticosterone levels measured 5 min later, but not 2 h after stressor exposure. In contrast, none of the stressors used influenced IL-1beta, IL-1 receptor antagonist, IL-1 receptor type I, IL-1 receptor accessory proteins I and II, or tumor necrosis factor-alpha mRNA levels in the prefrontal cortex, amygdala, hippocampus, or hypothalamus. Likewise, there were no stressor effects on transforming growth factor-beta1, neuropeptide Y, glycoprotein 130, or leptin receptor mRNAs in brain regions. Thus, the naturalistic/psychogenic stressor used does not affect any of the brain cytokine component mRNAs studied. It is suggested that this type of stressor activates homeostatic mechanisms (e.g., glucocorticoid release), which act to preclude brain cytokine alterations that would otherwise favor neuroinflammatory/neuroimmunological responses and the consequent increase of brain sensitivity to neurotoxic and neurodegenerative processes.

Autoregulation of the interleukin-1 system and cytokine-cytokine interactions in primary human astrocytoma cells.

Cytokines are proposed to play important roles in brain tumor biology. Previous studies reported on interleukin-1beta (IL-1beta) production and IL-1 receptor type I (IL-1RI, signaling receptor) expression in human astrocytomas, and on IL-1beta action in astrocytoma cell lines. However, all studies that have tested the direct action of cytokines have used exclusively astrocytoma cell lines, which do not recapitulate the in situ astrocytoma. Here, we demonstrate that astrocytoma cells obtained shortly after tumor neurosurgical resection respond to the direct application of human IL-1beta with a significant upregulation of IL-1alpha, IL-1beta, IL-1RI, and tumor necrosis factor-alpha (TNF-alpha) mRNAs. IL-1 receptor antagonist (IL-1Ra, an endogenous inhibitor that blocks IL-1alpha and IL-1beta actions) mRNA was not upregulated. Application of heat-inactivated IL-1beta had no effect on any cytokine component examined, demonstrating specificity of action. On the other hand, IL-1beta application did not modulate any cytokine component in acutely resected and dissociated primitive neuroectodermal tumor cells. The data have implications for a positive autoregulatory IL-1beta feedback system and synergistic IL-1beta <=> TNF-alpha interactions, which can be involved in the growth of pilocytic astrocytomas. The results together with our previous studies also support the notion that IL-1Ra or a compound with similar cytokine inhibitory activity could be useful for brain immunotherapy of astrocytomas.

Kindling modulates the IL-1beta system, TNF-alpha, TGF-beta1, and neuropeptide mRNAs in specific brain regions.

Cytokines and neuropeptides may be involved in seizure-associated processes. Following amygdala kindling in rats, we determined alterations of IL-1beta, IL-1 receptor antagonist (IL-1Ra), IL-1 receptor type I (IL-1RI), IL-1 receptor accessory proteins (IL-1R AcPs) I and II, TNF-alpha, TGF-beta1, neuropeptide Y (NPY), glycoprotein 130 (gp 130) and pro-opiomelanocortin (POMC) mRNA levels in the parietal, prefrontal and piriform cortices, amygdala, hippocampus and hypothalamus. Messenger RNAs expression in all brain regions was determined 2 h or 3 weeks following the last generalized convulsive seizure triggered from the ipsilateral kindled amygdala. The same brain region sample was used to assay for changes of all mRNA components. The results show that the 2 h-kindled group exhibited a significant up-regulation of IL-1beta, IL-1RI, TNF-alpha and TGF-beta1 mRNAs in all three cortical brain regions, amygdala and hippocampus. The largest up-regulation occurred in the prefrontal cortex (about 30-fold induction for IL-1beta and TNF-alpha mRNAs). IL-1R AcP I and II mRNA levels were also up-regulated in the cortical regions. No changes in IL-1beta, IL-1RI or TNF-alpha mRNA levels occurred in the 3 week-kindled group. NPY mRNA levels increased in the hippocampus, prefrontal and piriform cortices in the 2 h-kindled group, while IL-1Ra, gp 130, or POMC mRNA levels did not change in any group. The overall profile of mRNA changes shows specificity of transcriptional modulation induced by amygdala kindling. The data support a role of cytokines and NPY in the adaptive mechanisms associated with generalized seizure activity, with implications for neuroprotection, neuronal dysfunction and vulnerability associated with epileptic activity.

Two new diterpenoids, sarcophytins B and C, from the Indian Ocean soft coral Sarcophyton species.

Two new diterpenoids, sarcophytins B and C (1, 2), and the previously known sarcophytin (4) have been isolated from the Indian Ocean soft coral Sarcophyton sp. Structures of 1 and 2 were established by spectral data and supported by X-ray analysis of 1.

Feeding status and bacterial LPS-induced cytokine and neuropeptide gene expression in hypothalamus.

This study determined the effects of feeding status on basal and lipopolysaccharide (LPS)-stimulated cytokine and neuropeptide gene expression in the hypothalamus. With the use of RNase protection assays, we measured mRNA levels of interleukin-1beta (IL-1beta), IL-1 receptor antagonist (IL-1RA), IL-1 receptor type I (IL-1RI), IL-1R accessory proteins (AcP I and II), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta1 (TGF-beta1), glycoprotein 130 (Gp 130), leptin receptor (OB-R), neuropeptide Y (NPY), preprodynorphin, and proopiomelanocortin (POMC). Analyses were done in ad libitum-fed, fasted, and fasted and refed rats treated with the intracerebroventricular administration of physiological saline or LPS. The data show that food deprivation increases the basal mRNA expression of IL-1beta, IL-1RA, TNF-alpha, IL-1RI, and IL-1R AcP I, whereas mRNA levels of POMC showed a decrease. Five hours of refeeding returned cytokine levels to those observed in the ad libitum-fed group. LPS administration induced a robust upregulation of IL-1beta, TNF-alpha, and IL-1RI during all three feeding conditions. Acute food deprivation did not modulate LPS-induced changes in hypothalamic cytokine mRNA profiles. These findings show that 1) cytokine modulation occurs as an adaptive response to the stress of acute fasting and 2) acute fasting does not affect LPS-induced cytokine mRNA modulation in the hypothalamus. The data have implications to gram-negative infections associated with acute anorexia.

Persistent Borna disease virus infection of neonatal rats causes brain regional changes of mRNAs for cytokines, cytokine receptor components and neuropeptides.

Borna disease virus (BDV) replicates in brain cells. The neonatally infected rat with BDV exhibits developmental-neuromorphological abnormalities, neuronal cytolysis, and multiple behavioral and physiological alterations. Here, we report on the levels of interleukin-1beta (IL-1beta), IL-1 receptor antagonist (IL-1Ra), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta1 (TGF-beta1), IL-1 receptor type I (IL-1RI), IL-1 receptor accessory protein (IL-1R AcP) I and II, glycoprotein 130, and various neuropeptide mRNAs in the cerebellum, parieto-frontal cortex, hippocampus and hypothalamus of BDV-infected rats at 7 and 28 days postintracerebral BDV inoculation. The data show that cytokine and neuropeptide mRNA components are abnormal and differentially modulated in brain regions. IL-1beta, TNF-alpha and TGF-beta1 mRNA levels were up-regulated in all brain regions following BDV inoculation. The same cerebellar samples from BDV-infected animals exhibited the highest levels of IL-1beta, IL-1Ra, TNF-alpha, IL-1RI, and IL-1R AcP II mRNA expression. The profiles of IL-1beta, IL-1Ra, TNF-alpha, and TGF-beta1 mRNA induction in the cerebellar samples were highly intercorrelated, indicating an association among cytokine ligand mRNAs. Cytokine mRNA induction was differentially up-regulated among brain regions, except for TGF-beta1. Specificity of transcriptional changes in response to BDV infection is also suggested by the up-regulation of cytokine and neuropeptide Y mRNAs associated with down-regulation of pro-opiomelanocortin, and with no change of IL-1R AcPI, dynorphin and leptin receptor mRNAs in the same brain region samples. Other data also show a differential mRNA component modulation in distinct brain regions obtained from the same rats depending on the stage of BDV infection. The conclusion of these studies is that cytokines may play a role in the neuropathophysiology of neonatally BDV-infected rats.

Brain tumor development in rats is associated with changes in central nervous system cytokine and neuropeptide systems.

Cytokines have roles in tumor biology and induce neurological manifestations. Cytokines produced in response to a brain tumor may generate neurological manifestations via paracrine action. We investigated cytokine modulation in an in vivo brain tumor model with behavioral, morphological, and molecular approaches. Rat C6 glioma cells were implanted into the third cerebral ventricle of Wistar rats, their behavior was monitored, and the development of an intracranial tumor of astrocytic origin was confirmed by histology and positive immunostaining for vimentin, S-100 protein, and glial fibrillary acidic protein. Sensitive and specific RNase protection assays were used to analyze cytokine messenger RNA (mRNA) in brain regions from anorexic brain tumor-bearing animals. Brain tumor formation was associated with significant increased levels of interleukin (IL)-1beta, IL-1 receptor antagonist, IL-1 receptor type I, tumor necrosis factor (TNF)-alpha, and transforming growth factor (TGF)-beta1 mRNAs in the cerebellum, hippocampus, and hypothalamus. IL-1 receptor accessory proteins I and II mRNAs were increased in the cerebellum and hypothalamus. We also examined hypothalamic feeding-associated components: neuropeptide Y and proopiomelanocortin mRNAs were down-regulated, glycoprotein 130 mRNA levels were up-regulated, and leptin receptor (OB-R) mRNA levels were unchanged. These dissimilar profiles of mRNA expression suggest specificity of brain tumor-induced transcriptional changes. The data implicate cytokines as important factors in brain tumor-host interactions in vivo. The data also show that the C6 cell-induced glioma can be used as a behavioral-molecular model to study cytokine and neuropeptide modulation and action during the host biochemical and physiological responses to brain tumor development. Paracrine interactions seem pivotal because cytokine modulation was observed in various brain regions. These results also suggest that cytokine and neuropeptide changes during brain tumor progression are involved in brain tumor-associated neurological and neuropsychiatrical manifestations.

Basal and IL-1beta-stimulated cytokine and neuropeptide mRNA expression in brain regions of young and old Long-Evans rats.

Young and old Long-Evans rats respond with fevers of equal magnitude and duration to the brain administration of interleukin-1beta (IL-1beta). Here, we characterized brain regional mRNA expression of cytokine and neuropeptide components in response to the brain administration of IL-1beta. We used specific and highly sensitive RNase protection assays to determine mRNA changes for IL-1beta, IL-1 receptor type I (IL-1RI), IL-1R accessory proteins I and II (IL-1R AcP I and II), IL-1 receptor antagonist (IL-1Ra), transforming growth factor-beta1 (TGF-beta1), glycoprotein 130 (gp 130), leptin receptor (OB-R), neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) in the cerebellum, parieto-frontal cortex, hippocampus, hypothalamus, and midbrain of male young (3-5 months) and old (24-26 months) Long-Evans rats. In both young and old rats, IL-1beta induced a significant up-regulation of cerebellar IL-1Ra, IL-1RI, and TGF-beta1 mRNAs; hippocampal TGF-beta1 mRNA; hypothalamic IL-1beta, IL-1Ra, TGF-beta1, and gp 130 mRNAs; and midbrain IL-1beta and TGF-beta1 mRNAs. There were no age-related differences in any cytokine mRNA levels under basal or IL-1beta-stimulated conditions. Levels of hypothalamic POMC mRNA were different between age groups under basal and stimulated conditions. IL-1R AcP I and leptin receptor did not change in any brain region from either young or old rats, suggesting specificity of transcriptional changes. The data show that old Long-Evans rats are not defective in their capacity to develop an appropriate cytokine response to the brain administration of IL-1beta. The implications of these findings for neuroimmunological-neuroinflammatory and neurotoxic/neurodegenerative processes are discussed.

Gram-negative and gram-positive bacterial products induce differential cytokine profiles in the brain: analysis using an integrative molecular-behavioral in vivo model.

Bacterial-derived products [e.g., lipopolysaccharide (LPS) from Gram-negative and muramyl dipeptide (MDP) from Gram-positive bacteria] are proposed to play a pivotal role in the generation of neurological and neuroinflammatory/immunological responses during bacterial infections of the nervous system. LPS and MDP may act through cytokines; cytokine-neuropeptide interactions may also be involved. Here, we investigated cytokine and neuropeptide mRNA profiles in specific brain regions in response to the intracerebroventricular administration of LPS and MDP. IL-beta1 system components (ligand, signalling receptor, receptor accessory proteins, receptor antagonist), TNF-alpha, TGF-beta1, glycoprotein 130 (IL-6 receptor signal transducer), OB protein (leptin) receptor, neuropeptide Y, Y5 receptor, and pro-opiomelanocortin (opioid peptide precursor) mRNAs were analyzed. The same brain region sample was assayed for all components. LPS and MDP administration induced significantly different behavioral and molecular profiles. LPS was significantly more potent than MDP in inducing anorexia and in up-regulating pro-inflammatory cytokines (IL- beta1 and TNF-alpha mRNAs in the cerebellum, hippocampus and hypothalamus; MDP was more potent in up-regulating anti-inflammatory cytokine (IL-1 receptor antagonist and TGF-beta1) mRNAs. LPS and MDP also modulated hypothalamic IL-1 receptor mRNA components, but did not affect any of the neuropeptide-related components examined. The results suggest that the magnitude of neurological manifestations induced by LPS and MDP may involve the ratio between stimulatory and inhibitory cytokines, and this ratio may have implications for the neuroinflammatory/neurotoxic events associated with bacterial infections of the central nervous system.