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Cerebral inflammation with invasion of neutrophils and lymphocytes is a crucial factor in the process of secondary brain damage after traumatic brain injury (TBI). In TBI the intrinsic renin-angiotensin system is an important mediator of cerebral inflammation, as inhibition of the angiotensin II receptor type 1 (AT1) reduces secondary brain damage and the invasion of neutrophil granulocytes into injured cerebral tissue. The present study investigated the role of immune cells in AT1 inhibition-mediated neuroprotection after experimental TBI. In four different cohorts, male mice were studied to examine effects of neutropenia (anti-Ly6G antibody mediated neutrophil depletion; C57BL/6) or lymphopenia (RAG1 deficiency, RAG1-/-) alone, or in combination with candesartan-mediated AT1 inhibition. The present results demonstrate that reduction of neutrophils (neutrophil depletion in wild type mice) and of lymphocytes (RAG1-/-) as well as AT1 inhibition in (control antibody treated) wild type and RAG1-/- mice reduce brain damage and neuroinflammation after TBI compared to control groups, while in neutropenic mice, candesartan had no effect. However, AT1 inhibition was neuroprotective in RAG1-/- mice, but not in neutropenic mice. Therefore, the results indicate that AT1 inhibition mediated neuroprotection may be exerted by anti-inflammatory effects on neutrophils, with a subsequent reduction of neutrophil invasion.

Background The benzodiazepine midazolam is a γ-aminobutyric acid (GABA)-A receptor agonist frequently used for sedation or stress control in patients suffering from traumatic brain injury (TBI). However, experimental studies on benzodiazepines have reported divergent results, raising concerns about its widespread use in patients. Some studies indicate that benzodiazepine-mediated potentiation of GABAergic neurotransmission is detrimental in brain-injured animals. However, other experimental investigations demonstrate neuroprotective effects, especially in pretreatment paradigms. This study investigated whether single-bolus midazolam administration influences secondary brain damage post-TBI. Methods Two different midazolam dosages (0.5 and 5 mg/kg BW), a combination of midazolam and its competitive antagonist flumazenil, or vehicle solution (NaCl 0.9%) was injected intravenously to mice 24 h after experimental TBI induced by controlled cortical impact. Mice were evaluated for neurological and motor deficits using a 15-point neuroscore and the rotarod test. Histopathological brain damage and mRNA expression of inflammatory marker genes were analyzed using quantitative polymerase chain reaction three days after insult. Results Histological brain damage was not affected by posttraumatic midazolam administration. Midazolam impaired functional recovery, and this effect could not be counteracted by administering the midazolam antagonist flumazenil. An increase in IL-1β mRNA levels due to postinjury application of midazolam was reversible by flumazenil administration. However, other inflammatory parameters were not affected. Conclusions This study merely reports minor effects of a postinjury midazolam application. Further studies focusing on a time-dependent analysis of posttraumatic benzodiazepine administration are required.

Background: Cerebral inflammation with invasion of neutrophils and lymphocytes is an important factor in the process of secondary brain damage expansion after traumatic brain injury (TBI). Depletion of neutrophils in mice has been shown to reduce neurologic impairment after TBI. The intrinsic cerebral renin-angiotensin system is an important mediator of cerebral inflammation, as inhibition of the angiotensin II receptor type 1 (AT1) with candesartan improves neurologic recovery, and reduces secondary brain damage and cerebral neutrophil invasion after TBI. The present study was therefore designed to determine the role of immune cells in AT1 inhibition-mediated neuroprotection after TBI. Methods: In study A we assessed the effect of neutrophil depletion in mice after TBI. In study B we investigated the impact of RAG1 deficiency (RAG1-/-; mice without mature B- and T-lymphocytes) after TBI. In study C we investigated the role of neutrophils in candesartan mediated protection after TBI in wild-type mice with and without neutrophil depletion. In study D we examined the role of lymphocytes in AT1 inhibition mediated neuroprotection after TBI in RAG1-/-.Results: Neutropenic and RAG1-/- mice showed reduced brain damage compared to control groups. In control antibody treated wild type mice AT1 inhibition reduced lesion volumes and inflammation compared to vehicle, while in neutropenic mice, candesartan had no effect. In RAG1-/- mice AT1 inhibition resulted in reduction of brain damage and neuroinflammation compared to vehicle group. Conclusion: The present results demonstrate, that reduction of neutrophils and of lymphocytes as well as AT1 inhibition in wild type and RAG1-/- mice reduce brain damage and inflammation after TBI. However, AT1 inhibition was neuroprotective in RAG1-/- mice, but not in neutropenic mice. Therefore, the results indicate that AT1 inhibition mediated neuroprotection may be exerted by anti-inflammatory effects on neutrophils, with a subsequent reduction of neutrophil invasion.

Sağır, Özlem (Balikesir Author), Introduction More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. Methods and analysis EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. Ethics and dissemination EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369. ©

Background Prolonged time to extubation after general anaesthesia has been defined as a time from the end of surgery to airway extubation of at least 15 min. This occurrence can result in ineffective utilisation of operating rooms and delays in patient care. It is unknown if unanticipated delayed extubation is associated with escalation of care. Objectives To assess the frequency of 'prolonged extubation' after general anaesthesia and its association with 'escalation of care before discharge from the postanaesthesia care unit', defined as administration of reversal agents for opioids and benzodiazepines, airway re-intubation and need for ventilatory support. In addition, we tried to identify independent factors associated with 'prolonged extubation'. Design Single-centre retrospective study of cases performed from 1 January 2010 to 31 December 2014. Setting A large US tertiary academic medical centre. Patients Adult general anaesthesia cases excluding cardiothoracic, otolaryngology and neurosurgery procedures, classified as: Group 1 - regular extubation (≤15 min); Group 2 - prolonged extubation (≥16 and ≤60 min); Group 3 - very prolonged extubation (≥61 min). Main outcome measures First, cases with prolonged time to extubation; second, instances of escalation of care per extubation group; third, independent factors associated with prolonged time to extubation. Results A total of 86 123 cases were analysed. Prolonged extubation occurred in 8138 cases (9.5%) and very prolonged extubation in 357 cases (0.4%). In Groups 1, 2 and 3 respectively, naloxone was used in 0.4, 4.1 and 3.9% of cases, flumazenil in 0.03, 0.6 and 2% and respiratory support in 0.2, 0.7 and 2%, and immediate re-intubation occurred in 0.1, 0.3 and 2.8% of cases. Several patient-related, anaesthesia-related and procedure-related factors were independently associated with prolonged time to extubation. Conclusion Prolonged time to extubation occurred in nearly 10% of cases and was associated with an increased incidence of escalation of care. Many independent factors associated with 'prolonged extubation' were nonmodifiable by anaesthetic management.

Acute cerebral lesions are associated with dysregulation of brain glucose homeostasis. Previous studies showed that knockdown of Na+ -D-glucose cotransporter SGLT1 impaired outcome after middle cerebral artery occlusion and that widely expressed intracellular RS1 (RSC1A1) is involved in transcriptional and post-translational down-regulation of SGLT1. In the present study, we investigated whether SGLT1 is up-regulated during traumatic brain injury (TBI) and whether removal of RS1 in mice (RS1-KO) influences SGLT1 expression and outcome. Unexpectedly, brain SGLT1 mRNA in RS1-KO was similar to wild-type whereas it was increased in small intestine and decreased in kidney. One day after TBI, SGLT1 mRNA in the ipsilateral cortex was increased 160% in wild-type and 40% in RS1-KO. After RS1 removal lesion volume 1 day after TBI was reduced by 12%, brain edema was reduced by 28%, and motoric disability determined by a beam walking test was improved. In contrast, RS1 removal did neither influence glucose and glycogen accumulation 1 day after TBI nor up-regulation of inflammatory cytokines TNF-α, IL-1β and IL-6 or microglia activation 1 or 5 days after TBI. The data provide proof of principle that inhibition or down-regulation of SGLT1 by targeting RS1 in brain could be beneficial for early treatment of TBI.

Background A reliable measurement of brain water content (wet-to-dry ratio) is an important prerequisite for conducting research on mechanisms of brain edema formation. The conventionally used oven-drying method suffers from several limitations, especially in small samples. A technically demanding and time-consuming alternative is freeze-drying. New method Centrifugal vacuum concentrators (e.g. SpeedVac/speed-vacuum drying) are a combination of vacuum-drying and centrifugation, used to reduce the boiling temperature. These concentrators have the key advantages of improving the freeze-drying speed and maintaining the integrity of dried samples, thus, allowing e.g. DNA analyses. In the present study, we compared the heat-oven with speed-vacuum technique with regard to efficacy to remove moisture from water and brain samples and their effectiveness to distinguish treatment paradigms after experimental traumatic brain injury (TBI) caused by controlled cortical impact (CCI). Results Both techniques effectively removed water, the oven technique taking 24 h and vacuum-drying taking 48 h. Vacuum-drying showed lower variations in small samples (30–45 mg) and was suitable for genomic analysis as exemplified by sex genotyping. The effect of sodium bicarbonate (NaBic8.4%) on brain edema formation after CCI was investigated in small samples (2 × 1 mm). Only vacuum-drying showed low variation and significant improvement under NaBic8.4% treatment. Comparison with an existing method The receiver operating curves (ROC) analysis demonstrated that vacuum-drying (area under the curve (AUC):0.867-0.967) was superior to the conventional heat-drying method (AUC:0.367-0.567). Conclusions The vacuum method is superior in terms of quantifying water content in small samples. In addition, vacuum-dried samples can also be used for subsequent analyses, e.g., PCR analysis.

Background In animal research, authorities require a classification of anticipated pain levels and a perioperative analgesia protocol prior to approval of the experiments. However, data on this topic is rare and so is the reported use of analgesics. We determined surrogate parameters of pain and general well-being after subarachnoid hemorrhage (SAH), as well as the potential for improvement by different systemic analgesia paradigms. Brain injury was induced by filament perforation to mimic SAH. Sham-operated mice were included as surgical control groups with either neck or no-neck preparation. Mice with controlled cortical impact (CCI) injury were included as a control group with traumatic brain injury (TBI), but without neck preparation. Mice were randomized to buprenorphine, carprofen, meloxicam, or vehicle treatment. 24 h after SAH, CCI or sham surgery, pain and stress levels were assessed with a visual assessment score and the amount of food intake was recorded. Results Neck preparation, which is required to expose the surgical field for SAH induction, already increased pain/stress levels and sham surgeries for both CCI and SAH reduced food intake. Pain/stress levels were higher and food intake was lower after SAH compared with CCI. Pain/stress levels after CCI without analgesic treatment were similar to levels after SAH sham surgery. Pain treatment with buprenorphine was effective to reduce pain after SAH, whereas lower pain/stress intensity levels after CCI were not improved. Conclusion This study emphasizes the importance of pain and stress assessment after surgeries and the efficacy of buprenorphine to improve pain and comfort levels after experimental SAH.

This chapter focuses on brain trauma, which leads to a disruption of normal neurologic function. Before arrival in the hospital, a guideline-based treatment of traumatic brain injury (TBI) patients has to be initiated on-site. The patient then has to be transported to a specialized hospital equipped with a head computed tomography (CT), a neurosurgical department, and a neurointensive care unit. The chapter describes this process as well as the primary goals of maintaining an adequate perfusion and oxygenation of brain tissue. To achieve these goals, the intracranial pressure (ICP) and physiological variables should be kept within the normal range (homeostasis). This chapter also discusses complications like sepsis, pneumonia, and severe disturbances of coagulation, which should be prevented because they are independent predictors of adverse outcome.

Objectives:The gamma-aminobutyric acid modulator propofol induces neuronal cell death in healthy immature brains by unbalancing neurotrophin homeostasis via p75 neurotrophin receptor signaling. In adulthood, p75 neurotrophin receptor becomes down-regulated and propofol loses its neurotoxic effect. H

Traumatic brain injury (TBI) is a major cause of death and disability. The underlying pathophysiology is characterized by secondary processes including neuronal death and gliosis. To elucidate the role of the NG2 proteoglycan we investigated the response of NG2-knockout mice (NG2-KO) to TBI. Seven days after TBI behavioral analysis, brain damage volumetry and assessment of blood brain barrier integrity demonstrated an exacerbated response of NG2-KO compared to wild-type (WT) mice. Reactive astrocytes and expression of the reactive astrocyte and neurotoxicity marker Lcn2 (Lipocalin-2) were increased in the perilesional brain tissue of NG2-KO mice. In addition, microglia/macrophages with activated morphology were increased in number and mRNA expression of the M2 marker Arg1 (Arginase 1) was enhanced in NG2-KO mice. While TBI-induced expression of pro-inflammatory cytokine genes was unchanged between genotypes, PCR array screening revealed a marked TBI-induced up-regulation of the C-X-C motif chemokine 13 gene Cxcl13 in NG2-KO mice. CXCL13, known to attract immune cells to the inflamed brain, was expressed by activated perilesional microglia/macrophages seven days after TBI. Thirty days after TBI, NG2-KO mice still exhibited more pronounced neurological deficits than WT mice, up-regulation of Cxcl13, enhanced CD45+ leukocyte infiltration and a relative increase of activated Iba-1+/CD45+ microglia/macrophages. Our study demonstrates that lack of NG2 exacerbates the neurological outcome after TBI and associates with abnormal activation of astrocytes, microglia/macrophages and increased leukocyte recruitment to the injured brain. These findings suggest that NG2 may counteract neurological deficits and adverse glial responses in TBI.

Brain trauma triggers a cascade of deleterious events leading to enhanced incidence of drug resistant epilepsies, depression and cognitive dysfunctions. The underlying mechanisms leading to these alterations are poorly understood and treatment that attenuates those sequels not available. Using controlled-cortical impact (CCI) as experimental model of brain trauma in adult mouse we found a strong suppressive effect of the sodium-potassium-chloride importer (NKCC1) specific antagonist bumetanide on appearance of depression-like behavior. We demonstrate that this alteration in behavior is associated with a block of CCI-induced decrease in parvalbumin-positive interneurons and impairment of post-traumatic secondary neurogenesis within the dentate gyrus of the hippocampus. The mechanism mediating the effect of bumetanide involves early transient changes in expression of chloride regulatory proteins and qualitative changes in GABA(A) mediated transmission after brain trauma. This work opens new perspectives in the early treatment of human post-traumatic induced depression. Our results strongly suggest that bumetanide might constitute an efficient prophylactic treatment to reduce neurological and psychiatric consequences of brain trauma.

Traumatic brain injury (TBI) initiates an excessive mediator release of e.g. neurotrophins, which promote neuronal survival, differentiation, and modulate synaptic plasticity. Paradoxically, mature forms of neurotrophins promote neuronal survival, whereas unprocessed forms of neurotrophins induce cell death through p75 neurotrophin receptor (p75NTR) signaling. p75NTR is widely expressed during synaptogenesis and is subsequently downregulated in adulthood. Repair mechanisms after acute cerebral insults can reactivate its expression. Therefore, the influence of p75NTR on secondary brain damage was addressed. mRNA levels of p75NTR and its ligands were quantified in brain tissue up to 7 days after experimental TBI (controlled cortical impact; CCI). Brain damage, motor function and inflammatory marker gene expression were determined in mice lacking the proneurotrophin-binding site of the p75NTR protein (NGFR(-/-)) and wild type littermates (NGFR(+/+)) 24 h and 5 days after CCI. In addition, the effect of TAT-Pep5 (pharmacological inhibitor of the intracellular p75NTR death domain) on lesion volume was evaluated 24 h after insult. p75NTR mRNA levels were induced nine-fold by TBI. In NGFR(-/-) mice, lesion volume was reduced by 29% at 24 h and by 21% 5 days after CCI. Motor coordination was significantly improved 24 h after trauma compared with the wild type. Pharmacological inhibition of the p75NTR signaling reduced lesion volume by 18%. The present study presents first time evidence that genetic mutation of the neurotrophin interaction site of p75NTR strongly limits post-traumatic cell death. In addition, we revealed pharmacological targeting of the intracellular p75NTR cell death domain as a promising approach to limit acute brain damage.

Perioperative neurofunktionelle Storungen konnen u. a. als perioperativer Schlaganfall (POS) oder postoperatives kognitives Defizit (POCD) klinisch manifest werden. Da das Auftreten neurofunktioneller Storungen mit einer Verschlechterung der Prognose der Patienten assoziiert ist, stellt sich die Frage nach Moglichkeiten der Ursachenpravention bzw. Begrenzung der Symptomschwere und -dauer und den Moglichkeiten zur Verhinderung von Langzeitfolgen. Der Fokus des Ubersichtsartikels liegt auf der Darstellung von Moglichkeiten, durch intraoperatives anasthesiologisches Management Inzidenz und Ausmas neurologischer Komplikationen gunstig zu beeinflussen, um das Behandlungsergebnis im Sinne des Patienten zu optimieren.

Objectives: To determine the neuroprotective efficacy of the inert gas xenon following traumatic brain injury and to determine whether application of xenon has a clinically relevant therapeutic time window. Design: Controlled animal study. Setting: University research laboratory. Subjects: Male C57BL/6N mice (n = 196). Interventions: Seventy-five percent xenon, 50% xenon, or 30% xenon, with 25% oxygen (balance nitrogen) treatment following mechanical brain lesion by controlled cortical impact. Measurements and Main Results: Outcome following trauma was measured using 1) functional neurologic outcome score, 2) histological measurement of contusion volume, and 3) analysis of locomotor function and gait. Our study shows that xenon treatment improves outcome following traumatic brain injury. Neurologic outcome scores were significantly (p < 0.05) better in xenon-treated groups in the early phase (24 hr) and up to 4 days after injury. Contusion volume was significantly (p < 0.05) reduced in the xenon-treated groups. Xenon treatment significantly (p < 0.05) reduced contusion volume when xenon was given 15 minutes after injury or when treatment was delayed 1 or 3 hours after injury. Neurologic outcome was significantly (p < 0.05) improved when xenon treatment was given 15 minutes or 1 hour after injury. Improvements in locomotor function (p < 0.05) were observed in the xenon-treated group, 1 month after trauma. Conclusions: These results show for the first time that xenon improves neurologic outcome and reduces contusion volume following traumatic brain injury in mice. In this model, xenon application has a therapeutic time window of up to at least 3 hours. These findings support the idea that xenon may be of benefit as a neuroprotective treatment in patients with brain trauma.

HIF-1α is pivotal for cellular homeostasis in response to cerebral ischemia. Pharmacological inhibition of HIF-1α may reduce secondary brain damage by targeting post-translational mechanisms associated with its proteasomal degradation and nuclear translocation. This study examined the neuroprotective effects of 2-methoxyestradiol (2ME2), the involved HIF-1α-dependent response, and alternative splicing in exon 14 of HIF-1α (HIF-1α∆Ex14) after traumatic brain injury (TBI) in mice. Intraperitoneal 2ME2 administration 30 min after TBI caused a dose-dependent reduction in secondary brain damage after 24 h. 2ME2 was physiologically tolerated, showed no effects on immune cell brain migration, and mitigated trauma-induced brain expression of neuropathologically relevant HIF-1α target genes encoding for Plasminogen activator inhibitor 1 and tumor necrosis factor alpha. Moreover, TBI-induced expression of pro-apoptotic BNIP3 was attenuated by 2ME2 treatment. Alternatively, spliced HIF-1α∆Ex14 was substantially up-regulated from 6 to 48 h after TBI. In vitro, nuclear location and gene transcription activity of HIF-1α∆Ex14 were impaired compared to full-length HIF-1α, but no effects on nuclear translocation of the transcriptional complex partner HIF-1β were observed. This study demonstrates that 2ME2 confers neuroprotection after TBI. While the role of alternatively spliced HIF-1α∆Ex14 remains elusive, the in vivo data provide evidence that inhibition of a maladaptive HIF-1α-dependent response contributes to the neuroprotective effects of 2ME2. We examined neuroprotective effects of 2-methoxyestradiol (2ME2) and the hypoxia-inducible factor 1-α (HIF-1α) response following traumatic brain injury in mice. Early 2ME2 administration reduced the secondary brain damage and neuronal HIF-1α probably involving ubiquitin proteasome system-mediated degradation. The up-regulation of neuropathological HIF-1α target genes and pro-apoptotic BNIP3 protein was attenuated. We propose that the inhibition of a maladaptive HIF-1α response may contribute to 2ME2-mediated neuroprotection.

Objective: Limited data are available on the influence of sedation for critical care therapy with the widely used anesthetic propofol on recovery from acute traumatic brain injury. To establish the influence of propofol on endogenous neurogenesis and functional recovery after traumatic brain injury, rats were sedated with propofol either during or 2 hours after experimental traumatic brain injury. Design: Randomized controlled animal study. Setting: University research laboratory. Subjects: One hundred sixteen male Sprague Dawley rats. Interventions: Mechanical brain lesion by controlled cortical impact. Measurements and Main Results: This study investigated the dose-dependent influence of propofol (36 or 72 mg/kg/hr) either during controlled cortical impact induction or in a delayed application protocol 2 hours after experimental traumatic brain injury. Infusion of propofol resulted in 1) aggravation of neurologic dysfunction, 2) increased 28-day mortality rate, and 3) impaired posttraumatic neurogenesis (5-bromo-2-deoxyuridine + NeuN-positive cells). Application of propofol during trauma induction afforded a significant stronger effect in the high-dose group compared with low-dose propofol. In the posttrauma protocol, animals were sedated with sevoflurane during the controlled cortical impact injury, and propofol was given after an awake phase. In these animals, propofol increased mortality rate and impaired neurologic function and neurogenesis compared with animals without delayed propofol anesthesia. Conclusions: The results show that propofol may prevent or limit reparative processes in the early-phase postinjury. The results therefore indicate that anesthetics may be potentially harmful not only in very young mammalians but also in adult animals following acute cerebral injuries. The results provide first evidence for an altered sensitivity for anesthesia-related negative effects on neurogenesis, functional outcome, and survival in adult rats with brain lesions.

With a novel antibody against the rat Na+-d-glucose cotransporter SGLT2 (rSGLT2-Ab), which does not cross-react with rSGLT1 or rSGLT3, the ∼75-kDa rSGLT2 protein was localized to the brush-border membrane (BBM) of the renal proximal tubule S1 and S2 segments (S1 > S2) with female-dominant expression in adult rats, whereas rSglt2 mRNA expression was similar in both sexes. Castration of adult males increased the abundance of rSGLT2 protein; this increase was further enhanced by estradiol and prevented by testosterone treatment. In the renal BBM vesicles, the rSGLT1-independent uptake of [14C]-α-methyl-d-glucopyranoside was similar in females and males, suggesting functional contribution of another Na+-d-glucose cotransporter to glucose reabsorption. Since immunoreactivity of rSGLT2-Ab could not be detected with certainty in rat extrarenal organs, the SGLT2 protein was immunocharacterized with the same antibody in wild-type (WT) mice, with SGLT2-deficient ( Sglt2 knockout) mice as negative control. In WT mice, renal localization of mSGLT2 protein was similar to that in rats, whereas in extrarenal organs neither mSGLT2 protein nor mSglt2 mRNA expression was detected. At variance to the findings in rats, the abundance of mSGLT2 protein in the mouse kidneys was male dominant, whereas the expression of mSglt2 mRNA was female dominant. Our results indicate that in rodents the expression of SGLT2 is kidney-specific and point to distinct sex and species differences in SGLT2 protein expression that cannot be explained by differences in mRNA.

Perioperative neurofunctional disorders may become clinically apparent as e.g. perioperative stroke (POS) or postoperative cognitive deficit (POCD). Newly diagnosed neuro-functional disorders are associated with worsening of postoperative outcome. Focus of this review article is on the possibilities of the intraoperative anaesthesiological management to favourably influence incidence and severity of neurological complications and to improve postoperative outcome.

Accumulating evidence suggests a pivotal role of PDGFRß positive cells, a specific marker for central nervous system (CNS) pericytes, in tissue scarring. Identification of cells that contribute to tissue reorganization in the CNS upon injury is a crucial step to develop novel treatment strategies in regenerative medicine. It has been shown that pericytes contribute to scar formation in the spinal cord. It is further known that ischemia initially triggers pericyte loss in vivo, whilst brain trauma is capable of inducing pericyte detachment from cerebral vessels. These data point towards a significant role of pericytes in CNS injury. The temporal and spatial dynamics of PDGFRß cells and their responses in traumatic brain injury are poorly understood. Here we show that PDGFRß positive cells initially decline in the acute phase following experimental traumatic brain injury. However, PDGFRß positive cells increase significantly in the trauma zone days after brain injury. Using various pericyte markers we identify these cells to be pericytes that are demarcated by reactive gliosis. Our data indicate that brain trauma causes a biphasic response of pericytes in the early phase of brain trauma that may be of relevance for the understanding of pathological cellular responses in traumatic brain injury.

Robotic assisted prostatic surgery is frequently used because of its reduced side-effects compared with conventional surgery. During surgery, an extreme Trendelenburg position and CO2 pneumoperitoneum are necessary, which may lead to cerebral oedema, can potentially reduce brain perfusion and therefore could impair cerebral oxygenation. Cerebral oxygen saturation can be measured non-invasively using near-infrared spectroscopy (NIRS).The hypothesis of the present study was that steep Trendelenburg positioning during robotic assisted prostatic surgery impairs cerebral oxygen saturation measured using two different NIRS monitors.Clinical observational study.Primary care university hospital, study period from March 2012 to February 2013.A total of 29 patients scheduled for robotic assisted prostatic surgery in a steep Trendelenburg position.Cerebral oxygen saturation was measured throughout anaesthesia using the INVOS sensor (a trend monitor using two infrared wavelengths) for one hemisphere and the FORE-SIGHT sensor (a monitor using four wavelengths of laser light to calculate absolute oxygen saturation) for the other hemisphere in an alternate randomisation.Changes in cerebral oxygenation of more than 5% during surgery in the Trendelenburg position.The median duration of Trendelenburg positioning was 190 (interquartile range 130 to 230) min. Cerebral oxygen saturation decreased with INVOS from 74 ± 5% at baseline to a lowest value of 70 ± 4% with a slope of -0.0129 min(-1) (P0.01) and with FORE-SIGHT from 72 ± 5% at baseline to a nadir of 70 ± 3% with a slope of -0.008 min(-1) (P0.01). Comparing INVOS with FORE-SIGHT, there was a good association, with a slope of 0.86 ± 0.04 (P0.01).Both monitors showed a clinically irrelevant decrease in cerebral oxygen saturation of less than 5% over 4 h in a steep Trendelenburg position combined with CO2 pneumoperitoneum in patients undergoing robotic assisted prostatic surgery. This extreme positioning seems to be acceptable with regard to cerebral oxygenation.clinicaltrials.gov Identifier: ID NCT01275898.

Interscalene nerve blocks provide adequate analgesia, but there are no objective criteria for early assessment of correct catheter placement. In the present study, pulse oximetry technology was used to evaluate changes in the perfusion index (PI) in both blocked and unblocked arms, and changes in the plethysmographic variability index (PVI) were evaluated once mechanical ventilation was instituted.The PI and PVI values were assessed using a Radical-7™ finger pulse oximetry device (Masimo Corp., Irvine, CA, USA) in both arms of 30 orthopedic patients who received an interscalene catheter at least 25 min before induction of general anesthesia. Data were evaluated at baseline, on application of local anesthetics; five, ten, and 15 min after onset of interscalene nerve blocks; after induction of general anesthesia; before and after a 500 mL colloid fluid challenge; and five minutes thereafter.In the 25 patients with successful blocks, the difference between the PI values in the blocked arm and the PI values in the contralateral arm increased within five minutes of the application of the local anesthetics (P0.05) and increased progressively until 15 min. After induction of general anesthesia, the PI increased in the unblocked arm while it remained relatively constant in the blocked arm, thus reducing the difference in the PI. A fluid challenge resulted in a decrease in PVI values in both arms.The perfusion index increases after successful interscalene nerve blockade and may be used as an indicator for successful block placement in awake patients. The PVI values before and after a fluid challenge can be useful to detect changes in preload, and this can be performed in both blocked and unblocked arms.