scholarly journals Reduced GFAP Expression in Bergmann Glial Cells in the Cerebellum of Sigma-1 Receptor Knockout Mice Determines the Neurobehavioral Outcomes after Traumatic Brain Injury

2021 ◽  
Vol 22 (21) ◽  
pp. 11611
Author(s):  
Gundega Stelfa ◽  
Edijs Vavers ◽  
Baiba Svalbe ◽  
Rinalds Serzants ◽  
Anna Miteniece ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Glial Cells ◽  
Motor Coordination ◽  
Molecular Layer ◽  
Neurological Deficits ◽  
Sigma 1 Receptor ◽  
Gfap Expression ◽  
Bergmann Glial Cells ◽  
Sigma 1

Neuroprotective effects of Sigma-1 receptor (S1R) ligands have been observed in multiple animal models of neurodegenerative diseases. Traumatic brain injury (TBI)-related neurodegeneration can induce long-lasting physical, cognitive, and behavioral disabilities. The aim of our study was to evaluate the role of S1R in the development of neurological deficits after TBI. Adult male wild-type CD-1 (WT) and S1R knockout (S1R-/-) mice were subjected to lateral fluid percussion injury, and behavioral and histological outcomes were assessed for up to 12 months postinjury. Neurological deficits and motor coordination impairment were less pronounced in S1R-/- mice with TBI than in WT mice with TBI 24 h after injury. TBI-induced short-term memory impairments were present in WT but not S1R-/- mice 7 months after injury. Compared to WT animals, S1R-/- mice exhibited better motor coordination and less pronounced despair behavior for up to 12 months postinjury. TBI induced astrocyte activation in the cortex of WT but not S1R-/- mice. S1R-/- mice presented a significantly reduced GFAP expression in Bergmann glial cells in the molecular layer of the cerebellum compared to WT mice. Our findings suggest that S1R deficiency reduces TBI-induced motor coordination impairments by reducing GFAP expression in Bergmann glial cells in the cerebellum.

Sigma-1 Receptor Modulates Neuroinflammation After Traumatic Brain Injury

2015 ◽  
Vol 36 (5) ◽  
pp. 639-645 ◽  
Author(s):  
Hui Dong ◽  
Yunfu Ma ◽  
Zengxi Ren ◽  
Bin Xu ◽  
Yunhe Zhang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Sigma 1 Receptor ◽  
Sigma 1

scholarly journals Sigma-1 Receptor: A Potential Therapeutic Target for Traumatic Brain Injury

2021 ◽  
Vol 15 ◽  
Author(s):  
Mingming Shi ◽  
Fanglian Chen ◽  
Zhijuan Chen ◽  
Weidong Yang ◽  
Shuyuan Yue ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Endoplasmic Reticulum ◽  
Brain Injury ◽  
Neurological Disorders ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Glutamate Excitotoxicity ◽  
Sigma 1 Receptor ◽  
Beneficial Effects ◽  
Sigma 1

The sigma-1 receptor (Sig-1R) is a chaperone receptor that primarily resides at the mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) and acts as a dynamic pluripotent modulator regulating cellular pathophysiological processes. Multiple pharmacological studies have confirmed the beneficial effects of Sig-1R activation on cellular calcium homeostasis, excitotoxicity modulation, reactive oxygen species (ROS) clearance, and the structural and functional stability of the ER, mitochondria, and MAM. The Sig-1R is expressed broadly in cells of the central nervous system (CNS) and has been reported to be involved in various neurological disorders. Traumatic brain injury (TBI)-induced secondary injury involves complex and interrelated pathophysiological processes such as cellular apoptosis, glutamate excitotoxicity, inflammatory responses, endoplasmic reticulum stress, oxidative stress, and mitochondrial dysfunction. Thus, given the pluripotent modulation of the Sig-1R in diverse neurological disorders, we hypothesized that the Sig-1R may affect a series of pathophysiology after TBI. This review summarizes the current knowledge of the Sig-1R, its mechanistic role in various pathophysiological processes of multiple CNS diseases, and its potential therapeutic role in TBI.

scholarly journals Rhein Protects Against Neurological Deficits After Traumatic Brain Injury in Mice via Inhibiting Neuronal Pyroptosis

2020 ◽  
Vol 11 ◽  
Author(s):  
Fangfang Bi ◽  
Huaifen Ma ◽  
Chen Ji ◽  
Cuicui Chang ◽  
Wenbo Liu ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neurological Deficits

scholarly journals 299 PRE-084, A Sigma-1 Receptor Ligand, Protects Against Excitotoxic Perinatal Brain Injury in Newborn Mice

2012 ◽  
Vol 97 (Suppl 2) ◽  
pp. A87-A88
Author(s):  
E. Griesmaier ◽  
A. Posod ◽  
M. Gross ◽  
V. Neubauer ◽  
K. Wegleiter ◽  
...  
Keyword(s):  
Brain Injury ◽  
Perinatal Brain Injury ◽  
Receptor Ligand ◽  
Newborn Mice ◽  
Sigma 1 Receptor ◽  
Sigma 1

The Role of Inflammation in Traumatic Brain Injury

Neurotrauma ◽  
2018 ◽  
pp. 211-232
Author(s):  
Sarah C. Hellewell ◽  
Bridgette D. Semple ◽  
Jenna M. Ziebell ◽  
Nicole Bye ◽  
Cristina Morganti-Kossmann
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Glial Cells ◽  
Immune Cell ◽  
Brain Trauma ◽  
Multiple Roles ◽  
Cell Functions ◽  
Macrophage Populations

Inflammation occurring following brain trauma represents a significant constituent of complex secondary responses that dictate patients’ outcome. Although a few decades have passed since its discovery, new aspects of this intriguing phenomenon are still being uncovered, ranging from the multiple roles of mediators regulating the inception, progression, and resolution of neuroinflammation, to the development of antiinflammatory therapies. This review provides a summary of the vast research on traumatic brain injury inflammation. The authors describe the fundamental aspects of cytokine and immune cell functions, the orchestrated collaboration of chemokines and leukocytes, the phenotypic distinction of macrophage populations, and the contribution of glial cells. Among the beneficial properties of neuroinflammation, they briefly discuss cytokines’ impact on neurogenesis; the chapter concludes by touching on the implications of antiinflammatory therapies.

scholarly journals Annexin A2 Deficiency Exacerbates Neuroinflammation and Long-Term Neurological Deficits after Traumatic Brain Injury in Mice

2019 ◽  
Vol 20 (24) ◽  
pp. 6125 ◽  
Author(s):  
Ning Liu ◽  
Yinghua Jiang ◽  
Joon Yong Chung ◽  
Yadan Li ◽  
Zhanyang Yu ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Inflammatory Response ◽  
Neurovascular Unit ◽  
Annexin A2 ◽  
Tissue Loss ◽  
Neurological Deficits ◽  
Endogenous Factors ◽  
The Brain

Our laboratory and others previously showed that Annexin A2 knockout (A2KO) mice had impaired blood–brain barrier (BBB) development and elevated pro-inflammatory response in macrophages, implying that Annexin A2 (AnxA2) might be one of the key endogenous factors for maintaining homeostasis of the neurovascular unit in the brain. Traumatic brain injury (TBI) is an important cause of disability and mortality worldwide, and neurovascular inflammation plays an important role in the TBI pathophysiology. In the present study, we aimed to test the hypothesis that A2KO promotes pro-inflammatory response in the brain and worsens neurobehavioral outcomes after TBI. TBI was conducted by a controlled cortical impact (CCI) device in mice. Our experimental results showed AnxA2 expression was significantly up-regulated in response to TBI at day three post-TBI. We also found more production of pro-inflammatory cytokines in the A2KO mouse brain, while there was a significant increase of inflammatory adhesion molecules mRNA expression in isolated cerebral micro-vessels of A2KO mice compared with wild-type (WT) mice. Consistently, the A2KO mice brains had a significant increase in leukocyte brain infiltration at two days after TBI. Importantly, A2KO mice had significantly worse sensorimotor and cognitive function deficits up to 28 days after TBI and significantly larger brain tissue loss. Therefore, these results suggested that AnxA2 deficiency results in exacerbated early neurovascular pro-inflammation, which leads to a worse long-term neurologic outcome after TBI.

scholarly journals Concepts in Periodic Discharges: A Descriptive Study

2018 ◽  
Vol 05 (02) ◽  
pp. 068-074
Author(s):  
Laxmi Khanna ◽  
Nandini Agarwal ◽  
Sabita Kandel
Keyword(s):  
Traumatic Brain Injury ◽  
Status Epilepticus ◽  
Brain Injury ◽  
Multiorgan Failure ◽  
Autoimmune Encephalitis ◽  
Abnormal Behavior ◽  
Neurological Deficits ◽  
Eeg Monitoring ◽  
Herpes Encephalitis ◽  
Periodic Discharges

Abstract Introduction Periodic discharges are now known as the ictal–interictal continuum and represent ongoing injury in acute or chronic neurological illnesses. Objective The aim of our study was to identify periodic discharges in patients who have undergone continuous bedside electroencephalography (EEG) monitoring and to classify the EEG according to the current American Clinical Neurophysiology Society terminology. Materials and Methods The continuous bedside EEG records of intensive care patients admitted from August 2017 to July 2018 were analyzed. The clinical spectrum, the treatment, and outcome of each of these patients were monitored. Results Fifty cases of periodic discharges (11 children, 39 adults) were identified over 1 year from 2017 to 2018. The clinical presentation included 32% seizures, 16% status epilepticus, 20% coma, 16% fever with altered sensorium, 8% abnormal behavior, 4% strokes, and 4% traumatic brain injury. The diagnosis was 20% autoimmune encephalitis, 8% herpes encephalitis, 20% multiorgan failure, 4% traumatic brain injury, 16% status epilepticus, 16% posthypoxic encephalopathy, 4% strokes, 4% intracerebral bleeds, 4% meningitis, and 4% severe dementia. Lateralized periodic discharges were identified in 20%, bilateral independent periodic discharges in 20%, and generalized periodic discharges in 60%. Fifty-six percent patients recovered with residual neurological deficits and 44% succumbed to their illness. Conclusions Continuous bedside EEG monitoring has revolutionized the approach to seizures in critically ill patients. Despite a vigilant approach and diligent diagnosis of these abnormal rhythms, the mortality rate was 20% in patients with lateralized periodic discharges and 60% with bilateral and generalized periodic discharges (p ≤ 0.05).

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