scholarly journals Diagnostic and Therapeutic Potential of TSPO Studies Regarding Neurodegenerative Diseases, Psychiatric Disorders, Alcohol Use Disorders, Traumatic Brain Injury, and Stroke: An Update

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 870 ◽  
Author(s):  
Jasmina Dimitrova-Shumkovska ◽  
Ljupcho Krstanoski ◽  
Leo Veenman
Keyword(s):  
Cell Death ◽  
Brain Injury ◽  
Therapeutic Potential ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Cell Types ◽  
Translocator Protein ◽  
Brain Diseases ◽  
Positron Emission ◽  
The Brain

Neuroinflammation and cell death are among the common symptoms of many central nervous system diseases and injuries. Neuroinflammation and programmed cell death of the various cell types in the brain appear to be part of these disorders, and characteristic for each cell type, including neurons and glia cells. Concerning the effects of 18-kDa translocator protein (TSPO) on glial activation, as well as being associated with neuronal cell death, as a response mechanism to oxidative stress, the changes of its expression assayed with the aid of TSPO-specific positron emission tomography (PET) tracers’ uptake could also offer evidence for following the pathogenesis of these disorders. This could potentially increase the number of diagnostic tests to accurately establish the stadium and development of the disease in question. Nonetheless, the differences in results regarding TSPO PET signals of first and second generations of tracers measured in patients with neurological disorders versus healthy controls indicate that we still have to understand more regarding TSPO characteristics. Expanding on investigations regarding the neuroprotective and healing effects of TSPO ligands could also contribute to a better understanding of the therapeutic potential of TSPO activity for brain damage due to brain injury and disease. Studies so far have directed attention to the effects on neurons and glia, and processes, such as death, inflammation, and regeneration. It is definitely worthwhile to drive such studies forward. From recent research it also appears that TSPO ligands, such as PK11195, Etifoxine, Emapunil, and 2-Cl-MGV-1, demonstrate the potential of targeting TSPO for treatments of brain diseases and disorders.

scholarly journals p53-mediated neuronal cell death in ischemic brain injury

2010 ◽  
Vol 26 (3) ◽  
pp. 232-240 ◽  
Author(s):  
Li-Zhi Hong ◽  
Xiao-Yuan Zhao ◽  
Hui-Ling Zhang
Keyword(s):  
Cell Death ◽  
Brain Injury ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ischemic Brain Injury ◽  
Ischemic Brain

scholarly journals TNFα-induced AMPA-receptor trafficking in CNS neurons; relevance to excitotoxicity?

2004 ◽  
Vol 1 (3) ◽  
pp. 263-273 ◽  
Author(s):  
DMITRI LEONOUDAKIS ◽  
STEVEN P. BRAITHWAITE ◽  
MICHAEL S. BEATTIE ◽  
ERIC C. BEATTIE
Keyword(s):  
Cell Death ◽  
Inflammatory Response ◽  
Hippocampal Neurons ◽  
Neuronal Damage ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Cell Types ◽  
Synaptic Function ◽  
Ampar Trafficking ◽  
Novel Target

Injury and disease in the CNS increases the amount of tumor necrosis factor α (TNFα) that neurons are exposed to. This cytokine is central to the inflammatory response that occurs after injury and during prolonged CNS disease, and contributes to the process of neuronal cell death. Previous studies have addressed how long-term apoptotic-signaling pathways that are initiated by TNFα might influence these processes, but the effects of inflammation on neurons and synaptic function in the timescale of minutes after exposure are largely unexplored. Our published studies examining the effect of TNFα on trafficking of AMPA-type glutamate receptors (AMPARs) in hippocampal neurons demonstrate that glial-derived TNFα causes a rapid (<15 minute) increase in the number of neuronal, surface-localized, synaptic AMPARs leading to an increase in synaptic strength. This indicates that TNFα-signal transduction acts to facilitate increased surface localization of AMPARs from internal postsynaptic stores. Importantly, an excess of surface localized AMPARs might predispose the neuron to glutamate-mediated excitotoxicity and excessive intracellular calcium concentrations, leading to cell death. This suggests a new mechanism for excitotoxic TNFα-induced neuronal death that is initiated minutes after neurons are exposed to the products of the inflammatory response.Here we review the importance of AMPAR trafficking in normal neuronal function and how abnormalities that are mediated by glial-derived cytokines such as TNFα can be central in causing neuronal disorders. We have further investigated the effects of TNFα on different neuronal cell types and present new data from cortical and hippocampal neurons in culture. Finally, we have expanded our investigation of the temporal profile of the action of this cytokine relevant to neuronal damage. We conclude that TNFα-mediated effects on AMPAR trafficking are common in diverse neuronal cell types and very rapid in their onset. The abnormal AMPAR trafficking elicited by TNFα might present a novel target to aid the development of new neuroprotective drugs.

scholarly journals Neuronal apoptosis: signal and cell diversity

1969 ◽  
Vol 40 (1) ◽  
pp. 124-133
Author(s):  
Lina Vanessa Becerra ◽  
Hernán José Pimienta
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Neuronal Response ◽  
Neuronal Cell ◽  
Cell Types ◽  
Point Of View ◽  
Trophic Factors ◽  
Cell Diversity ◽  
Apoptotic Pathways ◽  
The Brain

Programmed cell death occurs as a physiological process during development. In the brain and spinal cord this event determines the number and location of the different cell types. In adulthood, programmed cell death or apoptosis is more restricted but it may play a major role in different acute and chronic pathological entities. However, in contrast to other tissues where apoptosis has been widely documented from a morphological point of view, in the central nervous system complete anatomical evidence of apoptosis is scanty. In spite of this there is consensus about the activation of different signal systems associated to programmed cell death. In the present article we attempt to summarize the main apoptotic pathways so far identified in nervous tissue. Considering that apoptotic pathways are multiple, the neuronal cell types are highly diverse and specialized and that neuronal response to injury and survival depends upon tissue context, (i.e., preservation of connectivity, glial integrity and cell matrix, blood supply and trophic factors availability) what is relevant for the apoptotic process in a sector of the brain may not be important in another.

scholarly journals Induction of the Nrf2 Pathway by Sulforaphane Is Neuroprotective in a Rat Temporal Lobe Epilepsy Model

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1702
Author(s):  
Sereen Sandouka ◽  
Tawfeeq Shekh-Ahmad
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Status Epilepticus ◽  
Temporal Lobe Epilepsy ◽  
Antioxidant Capacity ◽  
Temporal Lobe ◽  
Epileptiform Activity ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
The Brain

Epilepsy is a chronic disease of the brain that affects over 65 million people worldwide. Acquired epilepsy is initiated by neurological insults, such as status epilepticus, which can result in the generation of ROS and induction of oxidative stress. Suppressing oxidative stress by upregulation of the transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) has been shown to be an effective strategy to increase endogenous antioxidant defences, including in brain diseases, and can ameliorate neuronal damage and seizure occurrence in epilepsy. Here, we aim to test the neuroprotective potential of a naturally occurring Nrf2 activator sulforaphane, in in vitro epileptiform activity model and a temporal lobe epilepsy rat model. Sulforaphane significantly decreased ROS generation during epileptiform activity, restored glutathione levels, and prevented seizure-like activity-induced neuronal cell death. When given to rats after 2 h of kainic acid-induced status epilepticus, sulforaphane significantly increased the expression of Nrf2 and related antioxidant genes, improved oxidative stress markers, and increased the total antioxidant capacity in both the plasma and hippocampus. In addition, sulforaphane significantly decreased status epilepticus-induced neuronal cell death. Our results demonstrate that Nrf2 activation following an insult to the brain exerts a neuroprotective effect by reducing neuronal death, increasing the antioxidant capacity, and thus may also modify epilepsy development.

scholarly journals Ghrelin attenuates kainic acid-induced neuronal cell death in the mouse hippocampus

2010 ◽  
Vol 205 (3) ◽  
pp. 263-270 ◽  
Author(s):  
Jiyeon Lee ◽  
Eunjin Lim ◽  
Yumi Kim ◽  
Endan Li ◽  
Seungjoon Park
Keyword(s):  
Cell Death ◽  
Kainic Acid ◽  
Hippocampal Neurons ◽  
Therapeutic Potential ◽  
Excitatory Amino Acid ◽  
Neuroprotective Effect ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Proinflammatory Mediators ◽  
Hippocampal Neurodegeneration

Ghrelin is an endogenous ligand for GH secretagogue receptor type 1a (GHSR1a), and is produced and released mainly from the stomach. It has been recently demonstrated that ghrelin can function as a neuroprotective factor by inhibiting apoptotic pathways. Kainic acid (KA), an excitatory amino acid l-glutamate analog, causes neuronal death in the hippocampus; previous studies suggest that activated microglia and astrocytes actively participate in the pathogenesis of KA-induced hippocampal neurodegeneration. However, it is unclear whether ghrelin has neuroprotective effect in KA-induced hippocampal neurodegeneration. I.p. injection of KA produced typical neuronal cell death in the CA1 and CA3 pyramidal layers of the hippocampus, and the systemic administration of ghrelin significantly attenuated KA-induced neuronal cell death in these regions through the activation of GHSR1a. Ghrelin prevents KA-induced activation of microglia and astrocytes, and the expression of proinflammatory mediators tumor necrosis factor α, interleukin-1β, and cyclooxygenase-2. The inhibitory effect of ghrelin on the activation of microglia and astrocytes appears to be associated with the inhibition of matrix metalloproteinase-3 expression in damaged hippocampal neurons. Our data suggest that ghrelin has a therapeutic potential for suppressing KA-induced pathogenesis in the brain.

scholarly journals Disruption of Bax Protein Prevents Neuronal Cell Death but Produces Cognitive Impairment in Mice following Traumatic Brain Injury

2008 ◽  
Vol 25 (7) ◽  
pp. 755-767 ◽  
Author(s):  
Roya Tehranian ◽  
Marie E. Rose ◽  
Vincent Vagni ◽  
Alicia M. Pickrell ◽  
Raymond P. Griffith ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Cell Death ◽  
Cognitive Impairment ◽  
Brain Injury ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Bax Protein

scholarly journals Natural Products and Their Bioactive Compounds: Neuroprotective Potentials against Neurodegenerative Diseases

2020 ◽  
Vol 2020 ◽  
pp. 1-30 ◽  
Author(s):  
Nur Shafika Mohd Sairazi ◽  
K. N. S. Sirajudeen
Keyword(s):  
Cell Death ◽  
Natural Products ◽  
Neurodegenerative Diseases ◽  
Bioactive Compounds ◽  
Therapeutic Potential ◽  
Neuroprotective Effect ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Neuronal Structure ◽  
And Function

In recent years, natural products, which originate from plants, animals, and fungi, together with their bioactive compounds have been intensively explored and studied for their therapeutic potentials for various diseases such as cardiovascular, diabetes, hypertension, reproductive, cancer, and neurodegenerative diseases. Neurodegenerative diseases, including Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis are characterized by the progressive dysfunction and loss of neuronal structure and function that resulted in the neuronal cell death. Since the multifactorial pathological mechanisms are associated with neurodegeneration, targeting multiple mechanisms of actions and neuroprotection approach, which involves preventing cell death and restoring the function to damaged neurons, could be promising strategies for the prevention and therapeutic of neurodegenerative diseases. Natural products have emerged as potential neuroprotective agents for the treatment of neurodegenerative diseases. This review focused on the therapeutic potential of natural products and their bioactive compounds to exert a neuroprotective effect on the pathologies of neurodegenerative diseases.

Abstract P801: Impact of Oxidized Phospholipids on Outcomes From Cerebral Ischemia and Reperfusion Injury

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Jin Yu ◽  
Hong Zhu ◽  
Calvin Yeang ◽  
Joseph L Witztum ◽  
Sotirios Tsimikas ◽  
...  
Keyword(s):  
Cell Death ◽  
Cerebral Ischemia ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ischemia And Reperfusion ◽  
Oxidized Phospholipids ◽  
Ischemia And Reperfusion Injury ◽  
Cerebral Ischemia And Reperfusion ◽  
The Brain

The mechanisms leading to oxidative stress and cellular dysfunction during stroke are not well understood. To test the hypothesis that transient cerebral artery occlusion (MCAo) in mice results in the generation of oxidized phospholipids (oxPLs) that contribute to neuronal cell death and glial activation. Both in vitro and in vivo cerebral ischemia and reperfusion injury (IRI) resulted in the elevation of specific oxPLs. Neuronal cell death was determined in the presence of oxPLs and the natural oxPL E06 antibody protected the cells from the toxic effects. IRI in mice gave rise to increased immunoreactivity of oxPLs in the brain. E06 reduced inflammatory markers in the brain following IRI, including iba-1, GFAP and inflammatory cytokines. In addition, oxPLs gave rise to M1 and Mox microglial phenotypes which was reversed in the presence of E06 and elicited a more M2 phenotype. Nrf2 deficient mice show increased infarct volumes and microglia from Nrf2 -/- mice show a reduction in Mox gene expression, and E06 protects both mice and cells from the Nrf2 deficit. Cerebral IRI generates oxPLs which triggers neuronal cell loss and inflammation and inactivation of oxPLs in vivo reduces infarct volume and improves outcomes.

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