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Article ; Online: Neuroprotection and Beyond

Bashir Bietar / Sophie Tanner / Christian Lehmann

International Journal of Molecular Sciences, Vol 24, Iss 23, p

The Central Role of CB1 and CB2 Receptors in Stroke Recovery

2023 Volume 16728

Abstract: The endocannabinoid system, with its intricate presence in numerous cells, tissues, and organs, offers a compelling avenue for therapeutic interventions. Central to this system are the cannabinoid receptors 1 and 2 (CB1R and CB2R), whose ubiquity can ... ...

Abstract	The endocannabinoid system, with its intricate presence in numerous cells, tissues, and organs, offers a compelling avenue for therapeutic interventions. Central to this system are the cannabinoid receptors 1 and 2 (CB1R and CB2R), whose ubiquity can introduce complexities in targeted treatments due to their wide-ranging physiological influence. Injuries to the central nervous system (CNS), including strokes and traumatic brain injuries, induce localized pro-inflammatory immune responses, termed neuroinflammation. Research has shown that compensatory immunodepression usually follows, and these mechanisms might influence immunity, potentially affecting infection risks in patients. As traditional preventive treatments like antibiotics face challenges, the exploration of immunomodulatory therapies offers a promising alternative. This review delves into the potential neuroprotective roles of the cannabinoid receptors: CB1R’s involvement in mitigating excitotoxicity and CB2R’s dual role in promoting cell survival and anti-inflammatory responses. However, the potential of cannabinoids to reduce neuroinflammation must be weighed against the risk of exacerbating immunodepression. Though the endocannabinoid system promises numerous therapeutic benefits, understanding its multifaceted signaling mechanisms and outcomes remains a challenge.
Keywords	endocannabinoid system ; CB1 receptors ; CB2 receptors ; stroke recovery ; neuroinflammation ; immunomodulation ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	571
Language	English
Publishing date	2023-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cannabinoids and the Endocannabinoid System in Early SARS-CoV-2 Infection and Long COVID-19—A Scoping Review

Cassidy Scott / Stefan Hall / Juan Zhou / Christian Lehmann

Journal of Clinical Medicine, Vol 13, Iss 1, p

2023 Volume 227

Abstract: Coronavirus disease-19 (COVID-19) is a highly contagious illness caused by the SARS-CoV-2 virus. The clinical presentation of COVID-19 is variable, often including symptoms such as fever, cough, headache, fatigue, and an altered sense of smell and taste. ...

Abstract	Coronavirus disease-19 (COVID-19) is a highly contagious illness caused by the SARS-CoV-2 virus. The clinical presentation of COVID-19 is variable, often including symptoms such as fever, cough, headache, fatigue, and an altered sense of smell and taste. Recently, post-acute “long” COVID-19 has emerged as a concern, with symptoms persisting beyond the acute infection. Vaccinations remain one of the most effective preventative methods against severe COVID-19 outcomes and the development of long-term COVID-19. However, individuals with underlying health conditions may not mount an adequate protective response to COVID-19 vaccines, increasing the likelihood of severe symptoms, hospitalization, and the development of long-term COVID-19 in high-risk populations. This review explores the potential therapeutic role of cannabinoids in limiting the susceptibility and severity of infection, both pre- and post-SARS-CoV-19 infection. Early in the SARS-CoV-19 infection, cannabinoids have been shown to prevent viral entry, mitigate oxidative stress, and alleviate the associated cytokine storm. Post-SARS-CoV-2 infection, cannabinoids have shown promise in treating symptoms associated with post-acute long COVID-19, including depression, anxiety, post-traumatic stress injury, insomnia, pain, and decreased appetite. While current research primarily focuses on potential treatments for the acute phase of COVID-19, there is a gap in research addressing therapeutics for the early and post-infectious phases. This review highlights the potential for future research to bridge this gap by investigating cannabinoids and the endocannabinoid system as a potential treatment strategy for both early and post-SARS-CoV-19 infection.
Keywords	cannabidiol ; cannabinoids ; COVID-19 ; THC ; viral infection ; Medicine ; R
Language	English
Publishing date	2023-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Components of the Endogenous Cannabinoid System as Potential Biomarkers for Interstitial Cystitis/Bladder Pain Syndrome

Saki Sultana / Geraint Berger / Christian Lehmann

Diagnostics, Vol 12, Iss 19, p

2022 Volume 19

Abstract: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition causing bladder pressure and pain. The condition is of unknown etiology and is often accompanied by other symptoms, including chronic pelvic pain, increased urinary urgency, and ... ...

Abstract	Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition causing bladder pressure and pain. The condition is of unknown etiology and is often accompanied by other symptoms, including chronic pelvic pain, increased urinary urgency, and frequency. There is no definitive diagnosis for IC/BPS, and treatment options are currently limited to physical therapy and medications to help alleviate symptoms. The endogenous cannabinoid system (ECS) is an important regulator of numerous physiological systems, including the urinary system. Modulations of the ECS have been shown to be beneficial for IC/BPS-associated pain and inflammation in rodents. As an attempt to identify potential biomarkers for IC/BPS, we reviewed experimental studies where the components of the ECS have been quantified in experimental models of IC/BPS. Further investigations using well-defined animal models and patients’ data are required to obtain stronger evidence regarding the potential for ECS components to be definitive biomarkers for IC/BPS.
Keywords	endocannabinoid system ; interstitial cystitis ; bladder pain syndrome ; biomarker ; cannabinoid receptor ; endocannabinoid ligand ; Medicine (General) ; R5-920
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Microcirculatory Changes in Experimental Models of Stroke and CNS-Injury Induced Immunodepression

Sarah Lunardi Baccetto / Christian Lehmann

International Journal of Molecular Sciences, Vol 20, Iss 20, p

2019 Volume 5184

Abstract: Stroke is the second-leading cause of death globally and the leading cause of disability in adults. Medical complications after stroke, especially infections such as pneumonia, are the leading cause of death in stroke survivors. Systemic immunodepression ...

Abstract	Stroke is the second-leading cause of death globally and the leading cause of disability in adults. Medical complications after stroke, especially infections such as pneumonia, are the leading cause of death in stroke survivors. Systemic immunodepression is considered to contribute to increased susceptibility to infections after stroke. Different experimental models have contributed significantly to the current knowledge of stroke pathophysiology and its consequences. Each model causes different changes in the cerebral microcirculation and local inflammatory responses after ischemia. The vast majority of studies which focused on the peripheral immune response to stroke employed the middle cerebral artery occlusion method. We review various experimental stroke models with regard to microcirculatory changes and discuss the impact on local and peripheral immune response for studies of CNS-injury (central nervous system injury) induced immunodepression.
Keywords	stroke ; microcirculation ; inflammation ; immunodepression ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2019-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Inflammatory Response to Different Toxins in Experimental Sepsis Models

Kayle Dickson / Christian Lehmann

International Journal of Molecular Sciences, Vol 20, Iss 18, p

2019 Volume 4341

Abstract: Sepsis is defined as life-threatening organ dysfunction caused by the dysregulated host response to infection. Despite serious mortality and morbidity, no sepsis-specific drugs exist. Endotoxemia is often used to model the hyperinflammation associated ... ...

Abstract	Sepsis is defined as life-threatening organ dysfunction caused by the dysregulated host response to infection. Despite serious mortality and morbidity, no sepsis-specific drugs exist. Endotoxemia is often used to model the hyperinflammation associated with early sepsis. This model classically uses lipopolysaccharide (LPS) from Gram-negative pathogens to activate the immune system, leading to hyperinflammation, microcirculatory disturbances and death. Other toxins may also be used to activate the immune system including Gram-positive peptidoglycan (PG) and lipoteichoic acid (LTA). In addition to these standard toxins, other bacterial components can induce inflammation. These molecules activate different signaling pathways and produce different physiological responses which can be taken advantage of for sepsis modeling. Endotoxemia modeling can provide information on pathways to inflammation in sepsis and contribute to preclinical drug development.
Keywords	inflammation ; sepsis ; endotoxemia ; infection ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2019-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Intravital Imaging of Pulmonary Immune Response in Inflammation and Infection

Nazli Alizadeh-Tabrizi / Stefan Hall / Christian Lehmann

Frontiers in Cell and Developmental Biology, Vol

2021 Volume 8

Abstract: Intravital microscopy (IVM) is a unique imaging method providing insights in cellular functions and interactions in real-time, without the need for tissue extraction from the body. IVM of the lungs has specific challenges such as restricted organ ... ...

Abstract	Intravital microscopy (IVM) is a unique imaging method providing insights in cellular functions and interactions in real-time, without the need for tissue extraction from the body. IVM of the lungs has specific challenges such as restricted organ accessibility, respiratory movements, and limited penetration depth. Various surgical approaches and microscopic setups have been adapted in order to overcome these challenges. Among others, these include the development of suction stabilized lung windows and the use of more advanced optical techniques. Consequently, lung IVM has uncovered mechanisms of leukocyte recruitment and function in several models of pulmonary inflammation and infection. This review focuses on bacterial pneumonia, aspiration pneumonia, sepsis-induced acute lung Injury, and cystic fibrosis, as examples of lung inflammation and infection. In addition, critical details of intravital imaging techniques of the lungs are discussed.
Keywords	inflammation ; infection ; lung ; intravital microscopy ; leukocytes ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Iron Chelation in Local Infection

Cassidy Scott / Gaurav Arora / Kayle Dickson / Christian Lehmann

Molecules, Vol 26, Iss 189, p

2021 Volume 189

Abstract: Iron is an essential element in multiple biochemical pathways in humans and pathogens. As part of the innate immune response in local infection, iron availability is restricted locally in order to reduce overproduction of reactive oxygen species by the ... ...

Abstract	Iron is an essential element in multiple biochemical pathways in humans and pathogens. As part of the innate immune response in local infection, iron availability is restricted locally in order to reduce overproduction of reactive oxygen species by the host and to attenuate bacterial growth. This physiological regulation represents the rationale for the therapeutic use of iron chelators to support induced iron deprivation and to treat infections. In this review paper we discuss the importance of iron regulation through examples of local infection and the potential of iron chelation in treating infection.
Keywords	iron ; chelation ; local infection ; siderophores ; Organic chemistry ; QD241-441
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Effects of CNS Injury-Induced Immunosuppression on Pulmonary Immunity

Bashir Bietar / Christian Lehmann / Andrew W. Stadnyk

Life, Vol 11, Iss 576, p

2021 Volume 576

Abstract: Patients suffering from stroke, traumatic brain injury, or other forms of central nervous system (CNS) injury have an increased risk of nosocomial infections due to CNS injury-induced immunosuppression (CIDS). Immediately after CNS-injury, the response ... ...

Abstract	Patients suffering from stroke, traumatic brain injury, or other forms of central nervous system (CNS) injury have an increased risk of nosocomial infections due to CNS injury-induced immunosuppression (CIDS). Immediately after CNS-injury, the response in the brain is pro-inflammatory; however, subsequently, local and systemic immunity is suppressed due to the compensatory release of immunomodulatory neurotransmitters. CIDS makes patients susceptible to contracting infections, among which pneumonia is very common and often lethal. Ventilator-acquired pneumonia has a mortality of 20–50% and poses a significant risk to vulnerable patients such as stroke survivors. The mechanisms involved in CIDS are not well understood. In this review, we consolidate the evidence for cellular processes underlying the pathogenesis of CIDS, the emerging treatments, and speculate further on the immune elements at play.
Keywords	immunosuppression ; CNS-injury ; stroke ; pneumonia ; lung ; Science ; Q
Subject code	610
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Comparison of Treatment Effects of Different Iron Chelators in Experimental Models of Sepsis

Christian Lehmann / Maral Aali / Juan Zhou / Bruce Holbein

Life, Vol 11, Iss 1, p

2021 Volume 57

Abstract: Growing evidence indicates that dysregulated iron metabolism with altered and excess iron availability in some body compartments plays a significant role in the course of infection and sepsis in humans. Given that all bacterial pathogens require iron for ...

Abstract	Growing evidence indicates that dysregulated iron metabolism with altered and excess iron availability in some body compartments plays a significant role in the course of infection and sepsis in humans. Given that all bacterial pathogens require iron for growth, that iron withdrawal is a normal component of innate host defenses and that bacterial pathogens have acquired increasing levels of antibiotic resistance, targeting infection and sepsis through use of appropriate iron chelators has potential to provide new therapeutics. We have directly compared the effects of three Food and Drug Administration (FDA)-approved chelators (deferoxamine—DFO; deferiprone—DFP; and deferasirox—DFX), as were developed for treating hematological iron overload conditions, to DIBI, a novel purpose-designed, anti-infective and anti-inflammatory water-soluble hydroxypyridinone containing iron-selective copolymers. Two murine sepsis models, endotoxemia and polymicrobial abdominal sepsis, were utilized to help differentiate anti-inflammatory versus anti-infective activities of the chelators. Leukocyte adhesion, as measured by intravital microscopy, was observed in both models, with DIBI providing the most effective reduction and DFX the poorest. Inflammation in the abdominal sepsis model, assessed by cytokine measurements, indicated exacerbation by DFX and DFO for plasma Interleukin (IL)-6 and reductions to near-control levels for DIBI and DFP. Peritoneal infection burden was reduced 10-fold by DIBI while DFX and DFP provided no reductions. Overall, the results, together with those from other studies, revealed serious limitations for each of the three hematological chelators, i.e., as potentially repurposed for treating infection/sepsis. In contrast, DIBI provided therapeutic benefits, consistent with various in vitro and in vivo results from other studies, supporting the potential for its use in treating sepsis.
Keywords	iron ; iron chelation ; inflammation ; infection ; sepsis ; Science ; Q
Subject code	570
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Clinical features of pneumonia in severely malnourished children with diarrhoea compared to those without diarrhoea

Sufia Islam / Nishat Nasrin / Nigar Sultana Tithi / Christian Lehmann / Mohammod Jobayer Chisti

Frontiers in Bioscience-Landmark, Vol 26, Iss 10, Pp 717-

2021 Volume 722

Abstract: Introduction: Pneumonia and diarrhoea are amongst the most common causes for hospital admission for children in low- and middle-income countries such as Bangladesh. Undernourished children often have more severe infections and a higher morbidity and ... ...

Abstract	Introduction: Pneumonia and diarrhoea are amongst the most common causes for hospital admission for children in low- and middle-income countries such as Bangladesh. Undernourished children often have more severe infections and a higher morbidity and mortality. Objective: The objective of this study was to determine the clinical features and outcomes of pneumonia in severely malnourished children with and without diarrhoea. Methodology: A retrospective chart analysis was carried out on children under 5 years of age who were admitted in intensive care unit of the Dhaka hospital of International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b). A total of 245 severe acute malnourished children with pneumonia and diarrhoea (PD group) were compared with 89 children with pneumonia only (PO group). Results: A significantly higher number of children from the PD group had some/severe dehydration (16.3% vs. 1.1%; p < 0.005) when compared with children from the PO group. The PD group showed less cough (83.3% vs. 100%; p < 0.001), lower chest wall indrawing (40.4% vs. 60.7%; p = 0.001), and crackles (62.4% vs. 87.6%; p < 0.001) compared to the PO group at the time of admission. Conclusion: Early diagnosis and treatment of some/severe dehydration in addition to WHO recommended other routine treatment of diarrhoea, pneumonia and severe acute malnutrition in children may help to reduce childhood morbidity and mortality especially in low- and middle-income countries.
Keywords	pneumonia ; diarrhoea ; malnutrition ; children ; bangladesh ; Biochemistry ; QD415-436 ; Biology (General) ; QH301-705.5
Subject code	360
Language	English
Publishing date	2021-10-01T00:00:00Z
Publisher	IMR Press
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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