12 results on '"Rida Rehman"'
Search Results
2. Neuronal nuclear calcium signaling suppression of microglial reactivity is mediated by osteoprotegerin after traumatic brain injury
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Albrecht Fröhlich, Florian Olde Heuvel, Rida Rehman, Sruthi Sankari Krishnamurthy, Shun Li, Zhenghui Li, David Bayer, Alison Conquest, Anna M. Hagenston, Albert Ludolph, Markus Huber-Lang, Tobias Boeckers, Bernd Knöll, Maria Cristina Morganti-Kossmann, Hilmar Bading, and Francesco Roselli
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Traumatic brain injury ,Microglia ,Nuclear calcium ,Osteoprotegerin ,Synapses ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Traumatic brain injury (TBI) is characterized by massive changes in neuronal excitation, from acute excitotoxicity to chronic hyper- or hypoexcitability. Nuclear calcium signaling pathways are involved in translating changes in synaptic inputs and neuronal activity into discrete transcriptional programs which not only affect neuronal survival and synaptic integrity, but also the crosstalk between neurons and glial cells. Here, we report the effects of blunting neuronal nuclear calcium signals in the context of TBI. Methods We used AAV vectors to express the genetically encoded and nuclear-targeted calcium buffer parvalbumin (PV.NLS.mCherry) or the calcium/calmodulin buffer CaMBP4.mCherry in neurons only. Upon TBI, the extent of neuroinflammation, neuronal death and synaptic loss were assessed by immunohistochemistry and targeted transcriptome analysis. Modulation of the overall level of neuronal activity was achieved by PSAM/PSEM chemogenetics targeted to parvalbumin interneurons. The functional impact of neuronal nuclear calcium buffering in TBI was assessed by quantification of spontaneous whisking. Results Buffering neuronal nuclear calcium unexpectedly resulted in a massive and long-lasting increase in the recruitment of reactive microglia to the injury site, which was characterized by a disease-associated and phagocytic phenotype. This effect was accompanied by a substantial surge in synaptic loss and significantly reduced whisking activity. Transcriptome analysis revealed a complex effect of TBI in the context of neuronal nuclear calcium buffering, with upregulation of complement factors, chemokines and interferon-response genes, as well as the downregulation of synaptic genes and epigenetic regulators compared to control conditions. Notably, nuclear calcium buffering led to a substantial loss in neuronal osteoprotegerin (OPG), whereas stimulation of neuronal firing induced OPG expression. Viral re-expression of OPG resulted in decreased microglial recruitment and synaptic loss. OPG upregulation was also observed in the CSF of human TBI patients, underscoring its translational value. Conclusion Neuronal nuclear calcium signals regulate the degree of microglial recruitment and reactivity upon TBI via, among others, osteoprotegerin signals. Our findings support a model whereby neuronal activity altered after TBI exerts a powerful impact on the neuroinflammatory cascade, which in turn contributes to the overall loss of synapses and functional impairment.
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- 2022
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3. Acute TBK1/IKK-ε Inhibition Enhances the Generation of Disease-Associated Microglia-Like Phenotype Upon Cortical Stab-Wound Injury
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Rida Rehman, Lilla Tar, Adeyemi Jubril Olamide, Zhenghui Li, Jan Kassubek, Tobias Böckers, Jochen Weishaupt, Albert Ludolph, Diana Wiesner, and Francesco Roselli
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TBK1 ,microglia ,traumatic brain injury ,amlexanox ,neuroinflammation ,stab wound injury ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Traumatic brain injury has a poorer prognosis in elderly patients, possibly because of the enhanced inflammatory response characteristic of advanced age, known as “inflammaging.” Recently, reduced activation of the TANK-Binding-Kinase 1 (Tbk1) pathway has been linked to age-associated neurodegeneration and neuroinflammation. Here we investigated how the blockade of Tbk1 and of the closely related IKK-ε by the small molecule Amlexanox could modify the microglial and immune response to cortical stab-wound injury in mice. We demonstrated that Tbk1/IKK-ε inhibition resulted in a massive expansion of microglial cells characterized by the TMEM119+/CD11c+ phenotype, expressing high levels of CD68 and CD317, and with the upregulation of Cst7a, Prgn and Ccl4 and the decrease in the expression levels of Tmem119 itself and P2yr12, thus a profile close to Disease-Associated Microglia (DAM, a subset of reactive microglia abundant in Alzheimer’s Disease and other neurodegenerative conditions). Furthermore, Tbk1/IKK-ε inhibition increased the infiltration of CD3+ lymphocytes, CD169+ macrophages and CD11c+/CD169+ cells. The enhanced immune response was associated with increased expression of Il-33, Ifn-g, Il-17, and Il-19. This upsurge in the response to the stab wound was associated with the expanded astroglial scars and increased deposition of chondroitin-sulfate proteoglycans at 7 days post injury. Thus, Tbk1/IKK-ε blockade results in a massive expansion of microglial cells with a phenotype resembling DAM and with the substantial enhancement of neuroinflammatory responses. In this context, the induction of DAM is associated with a detrimental outcome such as larger injury-related glial scars. Thus, the Tbk1/IKK-ε pathway is critical to repress neuroinflammation upon stab-wound injury and Tbk1/IKK-ε inhibitors may provide an innovative approach to investigate the consequences of DAM induction.
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- 2021
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4. Adapting Grice Maxims in Teaching of Writing at Undergraduate Level: A Case Study
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Muhammad Ajmal, Afsheen Salahuddin, and Rida Rehman
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General Medicine - Abstract
This research aims to investigate the effectiveness of adapting Grice Maxims in teaching writing at undergraduate level, using a case study approach at Qurtuba University D. I. Khan. The study explores whether teaching writing by emphasizing the principles of relevance, quality, and clarity-which are the key principles of Grice Maxims can improve the quality of writing among undergraduate students. The population of the study is a class of 36 students of BS English enrolled in 2nd semester and 4 teachers who teach various subjects. The study employs a mixed-methods approach, which involves quantitative data collected through pre and post-tests from students, and qualitative data collected through interviews with teachers. The results suggest that using Grice Maxims in teaching writing has a positive impact on students' writing quality, as well as their perception of the writing process. The study concludes that incorporating Grice Maxims into the teaching of writing is a promising pedagogical approach that can enhance writing skills among undergraduate students.
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- 2023
5. Development of Stressor Scale for Obese People
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Rida Rehman and Tazvin Ijaz
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Distress ,Cronbach's alpha ,Scale (social sciences) ,Stressor ,Psychology ,Mental health ,General Psychology ,Structural equation modeling ,Exploratory factor analysis ,Confirmatory factor analysis ,Clinical psychology - Abstract
Present study was conducted to develop and validate an Indigenous scale to assess the stressors experienced by obese people in different domains of their lives. Mixed method design and purposive sampling technique was used. A list of 29 items was generated after thorough review of the literature and from the details of the interviews conducted with the participants. Validation from expert clinical psychologists was obtained. Exploratory factor analysis (EFA) with oblimin rotation was run on a sample of 300 participants for current study. Confirmatory factor analysis on a separate sample of 400 participants yielded a good model fit and validated three-factor structure with fit indices ? 2 = 807.45 (df = 320, N = 300), p < .05, RMSEA = .062, CFI = .91 and TLI = .88. The Cronbach alpha valuewas.86 indicating strong internal consistency of the scale. The distress and Well-being subscales of Mental Health Inventory were utilized to assess the convergent and divergent Validity which yielded positive and negative correlation respectively affirming Stressor Scale for Obese people as a valid construct. The study is an initial step to highlight and understand the stressors experienced by obese people and its severity level. This will help doctors and mental health professional to devise effective management of obesity.
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- 2021
6. The Theatre of Historical Revision: An Analysis of the Native American Drama Tradition
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Neelum Almas, Rida Rehman, and Amer Akhtar
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Literature ,History ,Native american ,business.industry ,business ,Drama - Abstract
We attempt to analyse the form and content of major Native American plays to discuss their relationship with the traditional English drama and its content. By looking at plays of key Native American playwrights, we show that the Native American tradition goes against the English tradition of drama in its form by challenging the unities of time and place and characterization. It also brings in elements of Native American tradition of storytelling such as the blend of the sacred and the profane, the use of humor, the attitude towards facticity, to the tradition of drama to carve out a unique space for itself through which it attempts to challenge the dominant narratives of history, Native American culture, and at the same time highlight the problems the Native American nations face currently.
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- 2021
7. Met/HGFR triggers detrimental reactive microglia in TBI
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Rida Rehman, Michael Miller, Sruthi Sankari Krishnamurthy, Jacob Kjell, Lobna Elsayed, Stefanie M. Hauck, Florian olde Heuvel, Alison Conquest, Akila Chandrasekar, Albert Ludolph, Tobias Boeckers, Medhanie A. Mulaw, Magdalena Goetz, Maria Cristina Morganti-Kossmann, Aya Takeoka, and Francesco Roselli
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Neuroscience [CP] ,phosphorylation ,traumatic brain injury ,HGFR ,microglia ,antibody array ,General Biochemistry, Genetics and Molecular Biology ,neuroinflammation ,Mice, Inbred C57BL ,VEGFR ,Mice ,Disease Models, Animal ,Neuroscience ,Hgfr ,Met ,Microglia ,Neuroinflammation ,Phosphorylation ,Proteomics ,Traumatic Brain Injury ,Vegfr [Antibody Array ,Btk ,Cp] ,proteomics ,Brain Injuries, Traumatic ,Humans ,Animals ,ddc:610 ,Signal Transduction - Abstract
The complexity of signaling events and cellular responses unfolding in neuronal, glial, and immune cells upon traumatic brain injury (TBI) constitutes an obstacle in elucidating pathophysiological links and targets for intervention. We use array phosphoproteomics in a murine mild blunt TBI to reconstruct the temporal dynamics of tyrosine-kinase signaling in TBI and then scrutinize the large-scale effects of perturbation of Met/HGFR, VEGFR1, and Btk signaling by small molecules. We show Met/HGFR as a selective modifier of early microglial response and that Met/HGFR blockade prevents the induction of microglial inflammatory mediators, of reactive microglia morphology, and TBI-associated responses in neurons and vasculature. Both acute and prolonged Met/HGFR inhibition ameliorate neuronal survival and motor recovery. Early elevation of HGF itself in the cerebrospinal fluid of TBI patients suggests that this mechanism has translational value in human subjects. Our findings identify Met/HGFR as a modulator of early neuroinflammation in TBI with promising translational potential. ispartof: Cell Reports vol:41 issue:13 ispartof: location:United States status: published
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- 2022
8. Interleukin-13 and its receptor are synaptic proteins involved in plasticity and neuroprotection
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Shun Li, Florian olde Heuvel, Rida Rehman, Zhenghui Li, Oumayma Aousji, Albrecht Froehlich, Wanhong Zhang, Alison Conquest, Sarah Woelfle, Michael Schoen, Caitlin O’Meara, Richard Lee Reinhardt, David Voehringer, Jan Kassubek, Albert Ludolph, Markus Huber-Lang, Bernd Knöll, Maria Cristina Morganti-Kossmann, Tobias Boeckers, and Francesco Roselli
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nervous system - Abstract
Immune system molecules are expressed by neurons, often for unknown functions. We have identified IL-13 and its receptor IL-13Ra1 as neuronal, synaptic proteins in mouse, rat, and human brains, whose engagement upregulates the phosphorylation of NMDAR and AMPAR subunits and, in turn, increases synaptic activity and CREB-mediated transcription. We demonstrate that increased IL-13 is a hallmark of traumatic brain injury (TBI) in mice as well as in two distinct cohorts of human patients. We also provide evidence that IL-13 upregulation protects neurons from excitotoxic death. We show IL-13 upregulation occurring in several cohorts of human brain samples and in CSF. Thus, IL-13 is a previously unrecognized physiological modulator of synaptic physiology of neuronal origin, with implications for the establishment of synaptic plasticity and the survival of neurons under injury conditions. Furthermore, we suggest that the neuroprotection afforded through the upregulation of IL-13 represents a new entry point for interventions in the pathophysiology of TBI.
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- 2021
9. Differential effect of ethanol intoxication on peripheral markers of cerebral injury in murine blunt traumatic brain injury
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Akila Chandrasekar, Tobias M. Boeckers, Steffen Halbgebauer, Zhenghui Li, Florian olde Heuvel, Jin Zhang, Markus Huber-Lang, Rida Rehman, Albert C. Ludolph, Francesco Roselli, and Markus Otto
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medicine.medical_specialty ,Traumatic brain injury ,Enolase ,Biomedical Engineering ,Alcohol ,Dermatology ,Critical Care and Intensive Care Medicine ,S100B ,Gastroenterology ,chemistry.chemical_compound ,neurofilament light ,Internal medicine ,medicine ,Immunology and Allergy ,ddc:610 ,Claudin-5 ,Beta (finance) ,Ethanol ,business.industry ,medicine.disease ,Comorbidity ,nervous system diseases ,neuron-specific enolase ,Peripheral ,nervous system ,chemistry ,Emergency Medicine ,Biomarker (medicine) ,Surgery ,AcademicSubjects/MED00010 ,business ,Biomarkers ,Research Article - Abstract
Background Blood-based biomarkers have proven to be a reliable measure of the severity and outcome of traumatic brain injury (TBI) in both murine models and patients. In particular, neuron-specific enolase (NSE), neurofilament light (NFL) and S100 beta (S100B) have been investigated in the clinical setting post-injury. Ethanol intoxication (EI) remains a significant comorbidity in TBI, with 30–40% of patients having a positive blood alcohol concentration post-TBI. The effect of ethanol on blood-based biomarkers for the prognosis and diagnosis of TBI remains unclear. In this study, we investigated the effect of EI on NSE, NFL and S100B and their correlation with blood–brain barrier integrity in a murine model of TBI. Methods We used ultra-sensitive single-molecule array technology and enzyme-linked immunosorbent assay methods to measure NFL, NSE, S100B and claudin-5 concentrations in plasma 3 hours post-TBI. Results We showed that NFL, NSE and S100B were increased at 3 hours post-TBI. Interestingly, ethanol blood concentrations showed an inverse correlation with NSE but not with NFL or S100B. Claudin-5 levels were increased post-injury but no difference was detected compared to ethanol pretreatment. The increase in claudin-5 post-TBI was correlated with NFL but not with NSE or S100B. Conclusions Ethanol induces an effect on biomarker release in the bloodstream that is different from TBI not influenced by alcohol. This could be the basis of investigations into humans.
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- 2021
10. Differential effect of ethanol intoxication on peripheral markers of cerebral injury in murine blunt TBI
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Florian olde Heuvel, Steffen Halbgebauer, Markus Otto, Zhenghui Li, Akila Chandrasekar, Rida Rehman, Tobias M. Boeckers, Markus Huber-Lang, Albert C. Ludolph, Francesco Roselli, and Jin Zhang
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Oncology ,medicine.medical_specialty ,Cerebral injury ,Traumatic brain injury ,business.industry ,Enolase ,medicine.disease ,Comorbidity ,Pathophysiology ,nervous system diseases ,Peripheral ,nervous system ,Internal medicine ,medicine ,Biomarker (medicine) ,Ethanol intoxication ,business - Abstract
Blood-based biomarkers have proven to be a reliable measure of traumatic brain injury (TBI) severity and outcome, in both murine models and patients. In particular, neuron-specific enolase (NSE) and neurofilament light (NFL) have been investigated in the clinical setting post injury. Ethanol intoxication (EI) remains a significant comorbidity in TBI, with 30-40% of patients having a positive blood alcohol level (BAC) post TBI. The effect of ethanol on blood-based biomarkers on the prognosis and diagnosis of TBI remain unclear. In this study, we investigated the effect of EI on NSE and NFL and their correlation with blood-brain barrier (BBB) integrity in a murine model of TBI. We have used ultra-sensitive single molecule array technology (SIMOA) and ELISA methods to measure NFL, NSE and Claudin-5 concentrations in plasma 3h post TBI. We showed that both NFL and NSE were increased 3h post TBI. However, ethanol blood concentrations only showed an inverse correlation with NSE, but not NFL. Claudin-5 levels were increased post injury, but no difference was detected in EI. The Claudin-5 increase post TBI was correlated with NFL, but not with NSE. Thus, the data indicate that ethanol has a confined effect on biomarker release in the bloodstream and neuronal biomarkers reflect a different pathophysiology upon TBI.
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- 2020
11. The Neuroprotective Effect of Ethanol Intoxication in Traumatic Brain Injury Is Associated with the Suppression of ErbB Signaling in Parvalbumin-Positive Interneurons
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Birgit Linkus, Rida Rehman, Francesco Roselli, Annette Palmer, Markus Huber-Lang, Akila Chandrasekar, Albert C. Ludolph, Alberto Catanese, Martin Wepler, Peter Radermacher, Florian olde Heuvel, and Tobias M. Boeckers
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0301 basic medicine ,Traumatic brain injury ,Pharmacology ,Neuroprotection ,Receptor tyrosine kinase ,03 medical and health sciences ,Mice ,0302 clinical medicine ,ErbB ,Interneurons ,Brain Injuries, Traumatic ,Medicine ,Animals ,biology ,Ethanol ,business.industry ,Chemogenetics ,medicine.disease ,Comorbidity ,nervous system diseases ,ErbB Receptors ,030104 developmental biology ,Neuroprotective Agents ,nervous system ,biology.protein ,Neurology (clinical) ,business ,Ethanol intoxication ,Alcoholic Intoxication ,030217 neurology & neurosurgery ,Parvalbumin ,Signal Transduction - Abstract
Ethanol intoxication (EI) is a frequent comorbidity of traumatic brain injury (TBI), but the impact of EI on TBI pathogenic cascades and prognosis is unclear. Although clinical evidence suggests that EI may have neuroprotective effects, experimental support is, to date, inconclusive. We aimed at elucidating the impact of EI on TBI-associated neurological deficits, signaling pathways, and pathogenic cascades in order to identify new modifiers of TBI pathophysiology. We have shown that ethanol administration (5 g/kg) before trauma enhances behavioral recovery in a weight-drop TBI model. Neuronal survival in the injured somatosensory cortex was also enhanced by EI. We have used phospho-receptor tyrosine kinase (RTK) arrays to screen the impact of ethanol on TBI-induced activation of RTK in somatosensory cortex, identifying ErbB2/ErbB3 among the RTKs activated by TBI and suppressed by ethanol. Phosphorylation of ErbB2/3/4 RTKs were upregulated in vGlut2
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- 2018
12. Neuroinflammation after Traumatic Brain Injury Is Enhanced in Activating Transcription Factor 3 Mutant Mice
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Daniela Sinske, Melanie Haffner-Luntzer, Francesco Roselli, Bernd Knoell, Sofia Anastasiadou, Rida Rehman, Philip Foerstner, and Anita Ignatius
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0301 basic medicine ,Male ,Traumatic brain injury ,Activating transcription factor ,Inflammation ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Downregulation and upregulation ,Brain Injuries, Traumatic ,medicine ,Animals ,Neuroinflammation ,ATF3 ,Activating Transcription Factor 3 ,Microglia ,business.industry ,medicine.disease ,Mice, Mutant Strains ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,Cancer research ,Female ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Astrocyte - Abstract
Traumatic brain injury (TBI) induces a neuroinflammatory response resulting in astrocyte and microglia activation at the lesion site. This involves upregulation of neuroinflammatory genes, including chemokines and interleukins. However, so far, there is lack of knowledge on transcription factors (TFs) modulating this TBI-associated gene expression response. Herein, we analyzed activating transcription factor 3 (ATF3), a TF encoding a regeneration-associated gene (RAG) predominantly studied in peripheral nervous system (PNS) injury. ATF3 contributes to PNS axon regeneration and was shown before to regulate inflammatory processes in other injury models. In contrast to PNS injury, data on ATF3 in central nervous system (CNS) injury are sparse. We used Atf3 mouse mutants and a closed-head weight-drop-based TBI model in adult mice to target the rostrolateral cortex resulting in moderate injury severity. Post-TBI, ATF3 was upregulated already at early time points (i.e,. 1-4 h) post-injury in the brain. Mortality and weight loss upon TBI were slightly elevated in Atf3 mutants. ATF3 deficiency enhanced TBI-induced paresis and hematoma formation, suggesting that ATF3 limits these injury outcomes in wild-type mice. Next, we analyzed TBI-associated RAG and inflammatory gene expression in the cortical impact area. In contrast to the PNS, only some RAGs (Atf3, Timp1, and Sprr1a) were induced by TBI, and, surprisingly, some RAG encoding neuropeptides were downregulated. Notably, we identified ATF3 as TF-regulating proneuroinflammatory gene expression, including CCL and CXCL chemokines (Ccl2, Ccl3, Ccl4, and Cxcl1) and lipocalin. In Atf3 mutant mice, mRNA abundance was further enhanced upon TBI compared to wild-type mice, suggesting immune gene repression by wild-type ATF3. In accord, more immune cells were present in the lesion area of ATF3-deficient mice. Overall, we identified ATF3 as a new TF-mediating TBI-associated CNS inflammatory responses.
- Published
- 2018
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