adenosine-kinase and Epilepsy--Temporal-Lobe

adenosine-kinase has been researched along with Epilepsy--Temporal-Lobe* in 7 studies

Reviews

1 review(s) available for adenosine-kinase and Epilepsy--Temporal-Lobe

ArticleYear
Understanding the basic mechanisms underlying seizures in mesial temporal lobe epilepsy and possible therapeutic targets: a review.
    Journal of neuroscience research, 2012, Volume: 90, Issue:5

    Despite years of research, epilepsy remains a poorly understood disorder. In the past several years, work has been conducted on a variety of projects with the goal of better understanding the pathogenesis and progression of mesial temporal lobe epilepsy (MTLE), in particular, and how to exploit those properties to generate innovative therapies for treatment of refractory epilepsies. This review seeks to give an overview of common morphological and biochemical changes associated with epilepsy and proposed treatments to address those changes. Furthering the understanding of ictogenesis and epileptogenesis remains an important goal for scientists seeking to find more effective treatments for MTLE.

    Topics: Adenosine Kinase; Animals; Comprehension; Cytokines; Disease Models, Animal; Epilepsy, Temporal Lobe; Gliosis; Humans; Mossy Fibers, Hippocampal; Nerve Degeneration; Seizures

2012

Other Studies

6 other study(ies) available for adenosine-kinase and Epilepsy--Temporal-Lobe

ArticleYear
Ectopic expression of neuronal adenosine kinase, a biomarker in mesial temporal lobe epilepsy without hippocampal sclerosis.
    Neuropathology and applied neurobiology, 2023, Volume: 49, Issue:4

    Mesial temporal lobe epilepsy without hippocampal sclerosis (no-HS MTLE) refers to those MTLE patients who have neither magnetic resonance imaging (MRI) lesions nor definite pathological evidence of hippocampal sclerosis. They usually have resistance to antiepileptic drugs, difficulties in precise seizure location and poor surgical outcomes. Adenosine is a neuroprotective neuromodulator that acts as a seizure terminator in the brain. The role of adenosine in no-HS MTLE is still unclear. Further research to explore the aetiology and pathogenesis of no-HS MTLE may help to find new therapeutic targets.. In surgically resected hippocampal specimens, we examined the maladaptive changes of the adenosine system of patients with no-HS MTLE. In order to better understand the dysregulation of the adenosine pathway in no-HS MTLE, we developed a rat model based on the induction of focal cortical lesions through a prenatal freeze injury.. We first examined the adenosine system in no-HS MTLE patients who lack hippocampal neuronal loss and found ectopic expression of the astrocytic adenosine metabolising enzyme adenosine kinase (ADK) in hippocampal pyramidal neurons, as well as downregulation of neuronal A. Ectopic expression of neuronal ADK might be a pathological hallmark of no-HS MTLE. Maladaptive changes in adenosine metabolism might be a novel target for therapeutic intervention in no-HS MTLE.

    Topics: Adenosine Kinase; Animals; Biomarkers; Ectopic Gene Expression; Epilepsy, Temporal Lobe; Hippocampal Sclerosis; Hippocampus; Magnetic Resonance Imaging; Rats; Sclerosis; Seizures

2023
Adenosine kinase and adenosine receptors A
    Epilepsia, 2020, Volume: 61, Issue:4

    In 75 cases, patients were stratified into high-risk (n = 16), medium-risk (n = 11) and low-risk (n = 48) categories according to the frequency of generalized seizures before surgery. Using whole-slide scanning Definiens image analysis we quantified the labeling index (LI) for ADK, A. A. Reduced cortical A

    Topics: Adenosine Kinase; Adult; Epilepsy, Temporal Lobe; Female; Hippocampus; Humans; Male; Receptor, Adenosine A1; Receptor, Adenosine A2A; Risk Factors; Sclerosis; Sudden Unexpected Death in Epilepsy

2020
Adenosine kinase, glutamine synthetase and EAAT2 as gene therapy targets for temporal lobe epilepsy.
    Gene therapy, 2014, Volume: 21, Issue:12

    Astrocytes are an attractive cell target for gene therapy, but the validation of new therapeutic candidates is needed. We determined whether adeno-associated viral (AAV) vector-mediated overexpression of glutamine synthetase (GS) or excitatory amino-acid transporter 2 (EAAT2), or expression of microRNA targeting adenosine kinase (miR-ADK) in hippocampal astrocytes in the rat brain could modulate susceptibility to kainate-induced seizures and neuronal cell loss. Transgene expression was found predominantly in astrocytes following direct injection of glial-targeting AAV9 vectors by 3 weeks postinjection. ADK expression in miR-ADK vector-injected rats was reduced by 94-96% and was associated with an ~50% reduction in the duration of kainate-induced seizures and greater protection of dentate hilar neurons but not CA3 neurons compared with miR-control vector-injected rats. In contrast, infusion of AAV-GS and EAAT2 vectors did not afford any protection against seizures or neuronal damage as the level of transcriptional activity of the glial fibrillary acidic promoter was too low to drive any significant increase in transgenic GS or EAAT2 relative to the high endogenous levels of these proteins. Our findings support ADK as a prime therapeutic target for gene therapy of temporal lobe epilepsy and suggest that alternative approaches including the use of stronger glial promoters are needed to increase transgenic GS and EAAT2 expression to levels that may be required to affect seizure induction and propagation.

    Topics: Adenosine Kinase; Animals; Astrocytes; Epilepsy, Temporal Lobe; Excitatory Amino Acid Transporter 2; Gene Expression Regulation; Gene Targeting; Genetic Therapy; Genetic Vectors; Glutamate-Ammonia Ligase; Hippocampus; Kainic Acid; Male; Neuroglia; Neurons; Rats; Rats, Sprague-Dawley; Seizures; Transgenes

2014
Upregulation of adenosine kinase in astrocytes in experimental and human temporal lobe epilepsy.
    Epilepsia, 2011, Volume: 52, Issue:9

    Adenosine kinase (ADK) represents the key metabolic enzyme for the regulation of extracellular adenosine levels in the brain. In adult brain, ADK is primarily present in astrocytes. Several lines of experimental evidence support a critical role of ADK in different types of brain injury associated with astrogliosis, which is also a prominent morphologic feature of temporal lobe epilepsy (TLE). We hypothesized that dysregulation of ADK is an ubiquitous pathologic hallmark of TLE.. Using immunocytochemistry and Western blot analysis, we investigated ADK protein expression in a rat model of TLE during epileptogenesis and the chronic epileptic phase and compared those findings with tissue resected from TLE patients with mesial temporal sclerosis (MTS).. In rat control hippocampus and cortex, a low baseline expression of ADK was found with mainly nuclear localization. One week after the electrical induction of status epilepticus (SE), prominent up-regulation of ADK became evident in astrocytes with a characteristic cytoplasmic localization. This increase in ADK persisted at least for 3-4 months after SE in rats developing a progressive form of epilepsy. In line with the findings from the rat model, expression of astrocytic ADK was also found to be increased in the hippocampus and temporal cortex of patients with TLE. In addition, in vitro experiments in human astrocyte cultures showed that ADK expression was increased by several proinflammatory molecules (interleukin-1β and lipopolysaccharide).. These results suggest that dysregulation of ADK in astrocytes is a common pathologic hallmark of TLE. Moreover, in vitro data suggest the existence of an additional layer of modulatory crosstalk between the astrocyte-based adenosine cycle and inflammation. Whether this interaction also can play a role in vivo needs to be further investigated.

    Topics: Adenosine Kinase; Animals; Astrocytes; Cells, Cultured; Disease Models, Animal; Electric Stimulation; Electroencephalography; Epilepsy, Temporal Lobe; Fetus; Glial Fibrillary Acidic Protein; Hippocampus; Humans; Interleukin-1beta; Lipopolysaccharides; Male; Rats; Rats, Sprague-Dawley; Temporal Lobe; Up-Regulation

2011
Astrogliosis in epilepsy leads to overexpression of adenosine kinase, resulting in seizure aggravation.
    Brain : a journal of neurology, 2005, Volume: 128, Issue:Pt 10

    Adenosine kinase (ADK) is considered to be the key regulator of the brain's endogenous anticonvulsant, adenosine. In adult brain, ADK is primarily expressed in a subpopulation of astrocytes and striking upregulation of ADK in these cells has been associated with astrogliosis after kainic acid-induced status epilepticus (KASE) in the kainic acid mouse model of temporal lobe epilepsy. To investigate the causal relationship between KASE-induced astrogliosis, upregulation of ADK and seizure activity, we have developed a novel mouse model [the Adktm1(-/-)-Tg(UbiAdk) mouse] lacking the endogenous astrocytic enzyme due to a targeted disruption of the endogenous gene, but containing an Adk transgene under the control of a human ubiquitin promoter. Mutant Adktm1(-/-)-Tg(UbiAdk) mice were characterized by increased brain ADK activity and constitutive overexpression of transgenic ADK throughout the brain, with particularly high levels in hippocampal pyramidal neurons. This ADK overexpression was associated with increased baseline levels of locomotion. Most importantly, two-thirds of the mutant mice analysed exhibited spontaneous seizure activity in the hippocampus and cortex. This was the direct consequence of transgene expression, since this seizure activity could be prevented by systemic application of the ADK inhibitor 5-iodotubercidin. Intrahippocampal injection of kainate in the mutant mice resulted in astrogliosis to the same extent as that observed in wild-type mice despite the absence of endogenous astrocytic ADK. Therefore, KASE-induced upregulation of endogenous ADK in wild-type mice is a consequence of astrogliosis. However, seizures in kainic acid-injected mutants displayed increased intra-ictal spike frequency compared with wild-type mice, indicating that, once epilepsy is established, increased levels of ADK aggravate seizure severity. We therefore conclude that therapeutic strategies that augment the adenosine system after astrogliosis-induced upregulation of ADK constitute a neurochemical rationale for the prevention of seizures in epilepsy.

    Topics: Adenosine Kinase; Animals; Astrocytes; Behavior, Animal; Brain; Cerebral Cortex; Disease Models, Animal; Electroencephalography; Enzyme Inhibitors; Epilepsy, Temporal Lobe; Gliosis; Hippocampus; Kainic Acid; Locomotion; Male; Mice; Mice, Transgenic; Neurons; Transgenes; Tubercidin; Up-Regulation

2005
Overexpression of adenosine kinase in epileptic hippocampus contributes to epileptogenesis.
    The Journal of neuroscience : the official journal of the Society for Neuroscience, 2004, Jan-21, Volume: 24, Issue:3

    Endogenous adenosine in the brain is thought to prevent the development and spread of seizures via a tonic anticonvulsant effect. Brain levels of adenosine are primarily regulated by the activity of adenosine kinase. To establish a link between adenosine kinase expression and seizure activity, we analyzed the expression of adenosine kinase in the brain of control mice and in a kainic acid-induced mouse model of mesial temporal lobe epilepsy. Immunohistochemical analysis of brain sections of control mice revealed intense staining for adenosine kinase, mainly in astrocytes, which were more or less evenly distributed throughout the brain, as well as in some neurons, particularly in olfactory bulb, striatum, and brainstem. In contrast, hippocampi lesioned by a unilateral kainic acid injection displayed profound astrogliosis and therefore a significant increase in adenosine kinase immunoreactivity accompanied by a corresponding increase of enzyme activity, which paralleled chronic recurrent seizure activity in this brain region. Accordingly, seizures and interictal spikes were suppressed by the injection of a low dose of the adenosine kinase inhibitor 5-iodotubercidin. We conclude that overexpression of adenosine kinase in discrete parts of the epileptic hippocampus may contribute to the development and progression of seizure activity.

    Topics: Action Potentials; Adenosine A1 Receptor Antagonists; Adenosine Kinase; Animals; Anticonvulsants; Astrocytes; Brain; Disease Models, Animal; Disease Progression; Electroencephalography; Enzyme Inhibitors; Epilepsy, Temporal Lobe; Glial Fibrillary Acidic Protein; Hippocampus; Immunohistochemistry; Kainic Acid; Mice; Neurons; Tubercidin; Xanthines

2004
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