Pleiotropic functions of TNF-α determine distinct IKKβ-dependent hepatocellular fates in response to LPS

2007 ◽  
Vol 292 (1) ◽  
pp. G242-G252 ◽  
Author(s):  
Rana Dajani ◽  
Salih Sanlioglu ◽  
Yulong Zhang ◽  
Qiang Li ◽  
Martha M. Monick ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Viral Vectors ◽  
Endotoxic Shock ◽  
Lethal Dose ◽  
Dominant Negative ◽  
Endotoxin Challenge ◽  
Lps Challenge ◽  
Differential Outcomes ◽  
Tnf Α ◽  
Pleiotropic Functions

TNF-α influences morbidity and mortality during the course of endotoxemia. However, the complex pleiotropic functions of TNF-α remain poorly understood. We evaluated how hepatic induction of NF-κB and TNF-α influence survival and hepatocellular death in a lethal murine model of endotoxic shock. Using dominant-negative viral vectors to inhibit the IKK complex, we demonstrate through this study that the liver is a major source of TNF-α during the course of lethal endotoxemia and that IKKβ (but not IKKα) is predominantly responsible for activating NF-κB and TNF-α in the liver after LPS administration. Using TNF-α knockout mice and hepatic-specific inhibition of IKKβ, we demonstrate that the status of TNF-α and NF-κB balances necrotic and apoptotic fates of hepatocytes in the setting of endotoxemia. In the presence of TNF-α, inhibiting hepatic IKKβ resulted in increased survival, reduced serum proinflammatory cytokines, and reduced hepatocyte necrosis in response to a lethal dose of endotoxin. In contrast, inhibiting hepatic IKKβ in TNF-α knockout mice resulted in decreased survival and increased caspase 3-mediated hepatocyte apoptosis after endotoxin challenge, despite a reduced proinflammatory cytokine response. In the presence of TNF-α, NF-κB-dependent hepatocellular necrosis predominated, while in the absence of TNF-α, NF-κB primarily influenced apoptotic fate of hepatocytes. Changes in JNK phosphorylation after LPS challenge were also dynamically affected by both IKKβ and TNF-α; however, this pathway could not solely explain the differential outcomes in hepatocellular fates. In conclusion, our studies demonstrate that induction of NF-κB and TNF-α balances protective (antiapoptotic) and detrimental (proinflammatory) pathways to determine hepatocellular fates during endotoxemia.

scholarly journals Susceptibility rhythm to bacterial endotoxin in myeloid clock-knockout mice

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Veronika Lang ◽  
Sebastian Ferencik ◽  
Bharath Ananthasubramaniam ◽  
Achim Kramer ◽  
Bert Maier
Keyword(s):  
Knockout Mice ◽  
Endotoxic Shock ◽  
Time Of Day ◽  
Conditional Knockout ◽  
Constant Darkness ◽  
Immune Functions ◽  
Lps Challenge ◽  
Circadian Time ◽  
Tnf Α ◽  
Circadian Physiology

Local circadian clocks are active in most cells of our body. However, their impact on circadian physiology is still under debate. Mortality by endotoxic (LPS) shock is highly time-of-day dependent and local circadian immune function such as the cytokine burst after LPS challenge has been assumed to be causal for the large differences in survival. Here, we investigate the roles of light and myeloid clocks on mortality by endotoxic shock. Strikingly, mice in constant darkness (DD) show a three-fold increased susceptibility to LPS as compared to mice in light-dark conditions. Mortality by endotoxic shock as a function of circadian time is independent of light-dark cycles as well as myeloid CLOCK or BMAL1 as demonstrated in conditional knockout mice. Unexpectedly, despite the lack of a myeloid clock these mice still show rhythmic patterns of pro- and anti-inflammatory cytokines such as TNF,α MCP-1, IL-18 and IL-10 in peripheral blood as well as time-of-day and site dependent traffc of myeloid cells. We speculate that systemic time-cues are sufficient to orchestrate innate immune response to LPS by driving immune functions such as cell traffcking and cytokine expression.

scholarly journals A conserved long noncoding RNA, GAPLINC, modulates the immune response during endotoxic shock

2021 ◽  
Vol 118 (7) ◽  
pp. e2016648118
Author(s):  
Apple Cortez Vollmers ◽  
Sergio Covarrubias ◽  
Daisy Kuang ◽  
Aaron Shulkin ◽  
Justin Iwuagwu ◽  
...  
Keyword(s):  
Immune Response ◽  
Knockout Mice ◽  
Noncoding Rna ◽  
Target Genes ◽  
Blood Clot ◽  
Multiorgan Failure ◽  
Endotoxic Shock ◽  
Negative Regulator ◽  
Inflammatory Genes ◽  
Lps Challenge

Recent studies have identified thousands of long noncoding RNAs (lncRNAs) in mammalian genomes that regulate gene expression in different biological processes. Although lncRNAs have been identified in a variety of immune cells and implicated in immune response, the biological function and mechanism of the majority remain unexplored, especially in sepsis. Here, we identify a role for a lncRNA—gastric adenocarcinoma predictive long intergenic noncoding RNA (GAPLINC)—previously characterized for its role in cancer, now in the context of innate immunity, macrophages, and LPS-induced endotoxic shock. Transcriptome analysis of macrophages from humans and mice reveals that GAPLINC is a conserved lncRNA that is highly expressed following macrophage differentiation. Upon inflammatory activation, GAPLINC is rapidly down-regulated. Macrophages depleted of GAPLINC display enhanced expression of inflammatory genes at baseline, while overexpression of GAPLINC suppresses this response. Consistent with GAPLINC-depleted cells, Gaplinc knockout mice display enhanced basal levels of inflammatory genes and show resistance to LPS-induced endotoxic shock. Mechanistically, survival is linked to increased levels of nuclear NF-κB in Gaplinc knockout mice that drives basal expression of target genes typically only activated following inflammatory stimulation. We show that this activation of immune response genes prior to LPS challenge leads to decreased blood clot formation, which protects Gaplinc knockout mice from multiorgan failure and death. Together, our results identify a previously unknown function for GAPLINC as a negative regulator of inflammation and uncover a key role for this lncRNA in modulating endotoxic shock.

scholarly journals Prenatal immune stimulation alters the postnatal acute phase and metabolic responses to an endotoxin challenge in weaned beef heifers,

2021 ◽  
Vol 5 (3) ◽  
Author(s):  
Jeffery A Carroll ◽  
Nicole C Burdick Sanchez ◽  
Paul R Broadway ◽  
Gleise M Silva ◽  
Juliana Ranches ◽  
...  
Keyword(s):  
Acute Phase ◽  
Treatment Time ◽  
Sickness Behavior ◽  
Metabolic Responses ◽  
Immune Stimulation ◽  
Endotoxin Challenge ◽  
Lps Challenge ◽  
Time Interaction ◽  
Tnf Α ◽  
Immunological Effects

Abstract This study evaluated whether administration of lipopolysaccharide (LPS) at each trimester of gestation would alter the acute phase (APR) and metabolic responses to a postnatal LPS challenge in weaned heifers. Pregnant crossbred multiparous cows (n = 50) were randomized into prenatal immune stimulation (PIS; n = 24; administered 0.1 µg/kg BW LPS subcutaneously at 71 ± 2, 170 ± 2 and 234 ± 2 d of gestation) and saline (CON; n = 26) groups. From these treatment groups, heifer calves (n = 12 PIS and 11 CON) were identified at weaning (244 ± 3 d of age) to receive an LPS challenge. On d 0, heifers were fitted with vaginal temperature (VT) devices, jugular catheters, and moved into individual stalls. On d 1, heifers were challenged i.v. with LPS (0.5 µg/kg BW) at 0 h. Blood samples were collected and sickness behavior scores (SBS) recorded at 0.5 h intervals from −2 to 8 h and at 24 h relative to LPS challenge. Serum was analyzed for cortisol, cytokines, glucose, non-esterified fatty acids (NEFA), and serum urea nitrogen (SUN) concentrations. Baseline VT was lesser in PIS heifers from −11 to −5 h pre-LPS (treatment × time: P < 0.01) compared to the CON; however, the post-LPS VT response did not differ between treatments (P = 0.89). There was a treatment × time interaction (P < 0.01) for SBS with PIS heifers having lesser SBS from 0.5 to 2 h post-LPS compared to CON. There was a treatment × time interaction (P = 0.03) for cortisol with PIS heifers having greater cortisol at 0.5, 3, 3.5, 5.5 and 6.5 h post-LPS compared to CON. There were treatment × time interactions for the post-LPS cytokine responses (P ≤ 0.05). Specifically, PIS heifers had greater TNF-α from 1.5 to 2 h, yet less TNF-α at 3 h than CON (P < 0.01), and PIS heifers had greater IFN-γ from 3.5 to 5.5 h post-LPS than CON (P < 0.01). In contrast, IL-6 was less in PIS than CON heifers from 1.5 to 8 h post-LPS (P < 0.001). Glucose concentrations were greater in PIS heifers at −1 h, but less at 2, 3 and 5.5 h compared to CON (treatment × time: P < 0.01). Serum NEFA concentrations were greater (P = 0.04) in PIS than CON heifers. There was a treatment × time interaction (P < 0.01) for SUN with PIS heifers having greater SUN concentrations at −2, −1.5, 2, 3, 6.5 and 24 h than CON. These data demonstrate that in utero exposure to multiple low doses of endotoxin has lasting physiological and immunological effects when the offspring encounter a similar postnatal immunological insult.

Scavenging nitric oxide reduces hepatocellular injury after endotoxin challenge

2001 ◽  
Vol 281 (1) ◽  
pp. G173-G181 ◽  
Author(s):  
Evan P. Nadler ◽  
Eva C. Dickinson ◽  
Donna Beer-Stolz ◽  
Sean M. Alber ◽  
Simon C. Watkins ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Serum Levels ◽  
No Production ◽  
Sprague Dawley ◽  
Hepatocellular Injury ◽  
Paramagnetic Resonance ◽  
Endotoxin Challenge ◽  
Lps Challenge ◽  
Tnf Α ◽  
Space Of Disse

Sustained upregulation of inducible nitric oxide (NO) synthase in the liver after endotoxin [lipopolysaccharide (LPS)] challenge may result in hepatocellular injury. We hypothesized that administration of a NO scavenger, NOX, may attenuate LPS-induced hepatocellular injury. Sprague-Dawley rats received NOX or saline via subcutaneous osmotic pumps, followed 18 h later by LPS challenge. Hepatocellular injury was assessed using biochemical assays, light, and transmission electron microscopy (TEM). Interleukin (IL)-6 mRNA was measured by RT-PCR. Tumor necrosis factor (TNF)-α protein expression was determined by immunohistochemistry. NOX significantly reduced serum levels of ornithine carbamoyltransferase and aspartate aminotransferase. TNF-α and IL-6 expression were increased in the livers of saline-treated but not NOX-treated rats. Although there was no difference between groups by light microscopy, TEM revealed obliteration of the space of Disse in saline-treated but not in NOX-treated animals. Electron paramagnetic resonance showed the characteristic mononitrosyl complex in NOX-treated rats. We conclude that NOX reduces hepatocellular injury after endotoxemia. NOX may be useful in the management of hepatic dysfunction secondary to sepsis or other diseases associated with excessive NO production.

scholarly journals SDZ MRL 953, A Novel Synthetic Lipid a Analogue, Induces Tolerance to the Lethal Effects of Endotoxin and Enhances Nonspecific Immunity

1992 ◽  
Vol 3 (suppl b) ◽  
pp. 94-100 ◽  
Author(s):  
Charles Lam ◽  
Eberhard Schütze ◽  
Emmanuel Quakyi ◽  
Ekke Liehl ◽  
Peter Stütz
Keyword(s):  
Lipid A ◽  
Endotoxic Shock ◽  
Lethal Dose ◽  
Peritoneal Macrophages ◽  
Attractive Alternative ◽  
Dependent Manner ◽  
E Coli ◽  
Microbial Inoculation ◽  
Lps Challenge ◽  
Immunosuppressed Patients

Despite the availability of potent antimicrobials, shock due to Gram-negative rod sepsis remains an important clinical concern in immunosuppressed patients. Current strategies for treating septic shock by removal of endotoxin (lipopolysaccharides [LPS]) or putative mediators have only been partially effective. An attractive alternative appears to be the induction of hyporesponsiveness to LPS by synthetic lipid A analogues. SDZ MRL 953, a novel prototype of lipid A analogues. was examined for its ability to induce early-phase tolerance against experimental endotoxemia in mice following single or multiple administrations 2, 24, or 72 h before challenge. The analogue protected mice against a lethal dose of LPS or infections in a time- and dose-dependent manner. Maximum effects were observed in animals pretreated with SDZ MRL 953 on three consecutive days before the LPS challenge or microbial inoculation. To examine the mechanisms involved, peritoneal macrophages from the tolerant mice were monitored ex v1vo for the release of tumour necrosis factor (TNF) and killing of an isolate of Escherichia coli. It was found that macrophages from endotoxin-tolerant mice produced only a fraction of the TNF released by cells from control groups in response to LPS. However, the killing of E coli by the macrophages was enhanced. In conclusion, SDZ MRL 953 may have a prophylactic potential in reducing the risk of endotoxic shock in traumatized or in myelosuppressed patients.

scholarly journals MAP kinase phosphatase 1 controls innate immune responses and suppresses endotoxic shock

2005 ◽  
Vol 203 (1) ◽  
pp. 131-140 ◽  
Author(s):  
Qun Zhao ◽  
Xianxi Wang ◽  
Leif D. Nelin ◽  
Yongxue Yao ◽  
Ranyia Matta ◽  
...  
Keyword(s):  
Map Kinase ◽  
Endotoxic Shock ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Wild Type ◽  
Kinase Activation ◽  
Lps Challenge ◽  
Map Kinase Phosphatase ◽  
Tnf Α ◽  
Severe Hypotension

Septic shock is a leading cause of morbidity and mortality. However, genetic factors predisposing to septic shock are not fully understood. Excessive production of proinflammatory cytokines, particularly tumor necrosis factor (TNF)-α, and the resultant severe hypotension play a central role in the pathophysiological process. Mitogen-activated protein (MAP) kinase cascades are crucial in the biosynthesis of proinflammatory cytokines. MAP kinase phosphatase (MKP)-1 is an archetypal member of the dual specificity protein phosphatase family that dephosphorylates MAP kinase. Thus, we hypothesize that knockout of the Mkp-1 gene results in prolonged MAP kinase activation, augmented cytokine production, and increased susceptibility to endotoxic shock. Here, we show that knockout of Mkp-1 substantially sensitizes mice to endotoxic shock induced by lipopolysaccharide (LPS) challenge. We demonstrate that upon LPS challenge, Mkp-1−/− cells exhibit prolonged p38 and c-Jun NH2-terminal kinase activation as well as enhanced TNF-α and interleukin (IL)-6 production compared with wild-type cells. After LPS challenge, Mkp-1 knockout mice produce dramatically more TNF-α, IL-6, and IL-10 than do wild-type mice. Consequently, Mkp-1 knockout mice develop severe hypotension and multiple organ failure, and exhibit a remarkable increase in mortality. Our studies demonstrate that MKP-1 is a pivotal feedback control regulator of the innate immune responses and plays a critical role in suppressing endotoxin shock.

scholarly journals Susceptibility rhythm to bacterial endotoxin in myeloid clock-knockout mice

2019 ◽  
Author(s):  
Veronika Lang ◽  
Sebastian Ferencik ◽  
Bharath Ananthasubramaniam ◽  
Achim Kramer ◽  
Bert Maier
Keyword(s):  
Knockout Mice ◽  
Endotoxic Shock ◽  
Time Of Day ◽  
Conditional Knockout ◽  
Constant Darkness ◽  
Cell Trafficking ◽  
Immune Functions ◽  
Lps Challenge ◽  
Circadian Time ◽  
Circadian Physiology

AbstractLocal circadian clocks are active in most cells of our body. However, their impact on circadian physiology is still under debate. Mortality by endotoxic (LPS) shock is highly time-of-day dependent and local circadian immune function such as the cytokine burst after LPS challenge has been assumed to be causal for the large differences in survival. Here, we investigate the roles of light and myeloid clocks on mortality by endotoxic shock. Strikingly, mice in constant darkness (DD) show a three-fold increased susceptibility to LPS as compared to mice in light-dark conditions. Mortality by endotoxic shock as a function of circadian time is independent of light-dark cycles as well as myeloid CLOCK or BMAL1 as demonstrated in conditional knockout mice. Unexpectedly, despite the lack of a myeloid clock these mice still show rhythmic patterns of pro- and anti-inflammatory cytokines such as TNFα, MCP-1, IL-18 and IL-10 in peripheral blood as well as time-of-day and site dependent traffic of myeloid cells. We speculate that systemic time-cues are sufficient to orchestrate innate immune response to LPS by driving immune functions such as cell trafficking and cytokine expression.

scholarly journals 233 NaturSafe® supplementation mitigates some aspects of the acute phase immune response to a lipopolysaccharide (LPS) challenge in weaned beef calves

2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 117-117
Author(s):  
Nicole C Burdick Sanchez ◽  
Jeffery A Carroll ◽  
Paul R Broadway ◽  
Tom S Edrington ◽  
Ilkyu Yoon ◽  
...  
Keyword(s):  
Acute Phase ◽  
Treatment Time ◽  
Sickness Behavior ◽  
Serum Cortisol ◽  
Post Challenge ◽  
Serum Samples ◽  
Lps Challenge ◽  
Time Interaction ◽  
Tnf Α ◽  
Monitoring Devices

Abstract This study was conducted to determine if feeding calves NaturSafe would reduce the acute phase response (APR) to lipopolysaccharide (LPS) challenge. Crossbred steers (n=32; 274±2 kg) were randomly allotted to two treatment diets: 1) Control, fed a standard receiving ration, and 2) NaturSafe, fed the Control ration supplemented with NaturSafe at 12 g/hd/d (NaturSafe®, Diamond V). On d22, steers were fitted with indwelling jugular catheters and rectal temperature monitoring devices and placed in individual stalls. On d23, steers were challenged i.v. with 0.25 µg/kg BW LPS. Serum samples were collected and sickness behavior scores (SBS) recorded at 0.5-h intervals from -2 to 8h and at 24h relative to LPS challenge. Rectal temperatures were greater (P=0.01) in NaturSafe compared to Control steers for the following time intervals following LPS challenge: 6 to 11h, 13h, 15 to 20h, and 22 to 24h. Additionally, SBS were reduced (P< 0.01) in NaturSafe compared to Control steers. White blood cell concentrations were greater (P=0.05) in NaturSafe compared to Control steers prior to the LPS challenge, yet the response to LPS did not differ between treatments (P >0.05). A treatment × time interaction for serum cortisol concentrations (P< 0.01) showed an increase at 0.5 and 2h post-challenge but a reduction at 3h in NaturSafe compared to Control steers. Additionally, fibrinogen was greater (P< 0.01) in NaturSafe compared to Control steers. There was a treatment × time interaction (P< 0.01) for TNF-α where concentrations were reduced from 1 to 2h post-challenge in NaturSafe compared to Control steers. Serum IL-6 tended (P=0.09) to show a reduction in serum concentrations in NaturSafe compared to Control steers. There was a tendency (P=0.07) for a treatment × time interaction for IFN-γ. Overall these data suggest a priming effect of NaturSafe on the innate immune system of steers, resulting in an attenuated APR to the LPS challenge.

scholarly journals PSIII-38 Butyric acid and derivatives: In vitro anti-inflammatory effects tested in porcine alveolar macrophages

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 370-370
Author(s):  
Lauren L Kovanda ◽  
Monika Hejna ◽  
Yanhong Liu
Keyword(s):  
Organic Acid ◽  
Butyric Acid ◽  
Sodium Butyrate ◽  
Alveolar Macrophages ◽  
Block Design ◽  
Lps Challenge ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Challenge Group

Abstract The aim of this experiment was to examine the anti-inflammatory effects of butyric acid, sodium butyrate, monobutyrin and tributyrin using porcine alveolar macrophages (PAMs). PAMs were isolated from the bronchial lavage of 6 piglets at 6 weeks of age, and then seeded at 106 cells/mL in 24-well plates. After 24 h incubation, cells were treated with different treatments in a randomized complete block design with 10 replicates. The treatments were in a factorial arrangement with 2 doses of lipopolysaccharide (LPS, 0 or 1 μg/mL) and 5 levels of organic acid (0, 0.5, 1, 2, 4 mM for butyric acid and tributyrin and 0, 1, 2, 4, 8 mM for sodium butyrate and monobutyrin). Supernatants were collected after another 24 h incubation and analyzed for tumor necrosis factor alpha (TNF-α). Cell viability was also tested by the MTT assay. Data were analyzed using the MIXED procedure of SAS. No cytotoxic effect was observed in LPS challenge and each organic acid with the percentage of live cells was more than 76% in comparison to the sham control. Sodium butyrate at 2 and 4 mM dose exhibited (P < 0.01) a stimulatory effect on cell proliferation. LPS challenge remarkably stimulated (P < 0.0001) TNF-α secretion from PAMs. In the non-challenge group, butyric acid, monobutyrin, and tributyrin linearly reduced TNF-α production from PAMs, whereas 2 mM sodium butyrate tended to increase (P = 0.056) TNF-α secretion from PAMs. In the LPS challenge group, all tested organic acid dose-dependently reduced (P < 0.001) TNF-α production from LPS-challenged PAMs, with the strongest inhibiting effect observed at the highest dose. Results indicated that butyric acid and its derivatives that were tested in the current experiment all had strong anti-inflammatory activities in vitro.

scholarly journals GMP-compliant fully automated radiosynthesis of [18F]FEPPA for PET/MRI imaging of regional brain TSPO expression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chi-Wei Chang ◽  
Chuang-Hsin Chiu ◽  
Ming-Hsien Lin ◽  
Hung-Ming Wu ◽  
Tsung-Hsun Yu ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Western Blotting ◽  
Second Generation ◽  
Mrna Levels ◽  
Automated Radiosynthesis ◽  
Lps Challenge ◽  
Tnf Α ◽  
The Brain ◽  
Tspo Expression

Abstract Background Expression of translocator protein (TSPO) on the outer mitochondrial membrane of activated microglia is strongly associated with neuroinflammation. The second-generation PET ligand [18F]FEPPA specifically binds TSPO to enable in vivo visualization and quantification of neuroinflammation. We optimized a fully automated radiosynthesis method and evaluated the utility of [18F]FEPPA, the second-generation PET ligand specifically binds TSPO, in a mouse model of systemic LPS challenge to detect TSPO-associated signals of central and peripheral inflammation. In vivo dynamic PET/MR imaging was performed in LPS-induced and control mice after [18F]FEPPA administration. The relationship between the [18F]FEPPA signal and the dose of LPS was assessed. The cytokine levels (i.e., TNF-α, Il-1β, Il-6) in LPS-induced mice were measured by RT-PCR. Standard uptake value (SUV), total volume of distribution (VT) and area under the curve (AUC) were determined based on the metabolite-uncorrected plasma input function. Western blotting and immunostaining were used to measure TSPO expression in the brain. Results The fully automated [18F]FEPPA radiosynthesis produced an uncorrected radiochemical yield of 30 ± 2% within 80 min, with a radiochemical purity greater than 99% and specific activity of 148.9‒216.8 GBq/µmol. Significant differences were observed in the brain after [18F]FEPPA administration: SUV, VT and AUC were 1.61 ± 0.1, 1.25 ± 0.12 and 1.58 ± 0.09-fold higher in LPS-injected mice than controls. TNF-α, Il-1β and Il-6 mRNA levels were also elevated in the brains of LPS-injected mice. Western blotting revealed TSPO (p < 0.05) and Iba-1 (p < 0.01) were upregulated in the brain after LPS administration. In LPS-injected mice, TSPO immunoactivity colocalized with Iba-1 in the cerebrum and TSPO was significantly overexpressed in the hippocampus and cerebellum. The peripheral organs (heart, lung) of LPS-injected mice had higher [18F]FEPPA signal-to-noise ratios than control mice. Conclusions Based on the current data on ligand specificity and selectivity in central tissues using 7 T PET/MR imaging, we demonstrate that [18F]FEPPA accumulations significant increased in the specific brain regions of systemic LPS-induced neuroinflammation (5 mg/kg). Future investigations are needed to determine the sensitivity of [18F]FEPPA as a biomarker of neuroinflammation as well as the correlation between the PET signal intensity and the expression levels of TSPO.

Sign in / Sign up

Export Citation Format

Share Document