Commonalities in epileptogenic processes from different acute brain insults: Do they translate?
| Autor: | Raymond Dingledine, Phillip L. Pearl, Henrik Klitgaard, Daniel H. Lowenstein, Christian Steinhäuser, Ingmar Blümcke, Robert S. Sloviter, Matti Sillanpää, Asla Pitkänen, Matthew C. Walker, Dieter Schmidt, Wolfgang Löscher, Annamaria Vezzani, Jerome Engel, Martin J. Brodie, Michael A. Rogawski, Katja Kobow, Eleonora Aronica, Amy R. Brooks-Kayal, Pavel Klein, Detlev Boison, Noora Puhakka, Rafal M. Kaminski, Christophe Bernard, Patrick A. Forcelli, Lawrence J. Hirsch |
|---|---|
| Přispěvatelé: | Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Předmět: |
0301 basic medicine
Biomedical antiepileptogenesis Neurodegenerative Epileptogenesis Translational Research Biomedical Epilepsy 0302 clinical medicine acquired epilepsy 2.1 Biological and endogenous factors Aetiology Stroke ComputingMilieux_MISCELLANEOUS traumatic brain injury stroke 3. Good health Astrogliosis CNS infections medicine.anatomical_structure Neurology Neurological medicine.symptom Physical Injury - Accidents and Adverse Effects Traumatic brain injury Central nervous system Clinical Sciences Status epilepticus Article Temporal lobe 03 medical and health sciences Translational Research medicine Animals Humans Traumatic Head and Spine Injury status epilepticus Neurology & Neurosurgery business.industry Animal [SCCO.NEUR]Cognitive science/Neuroscience Prevention Neurosciences medicine.disease Brain Disorders Disease Models Animal 030104 developmental biology Brain Injuries Disease Models epileptogenesis Neurology (clinical) business Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Epilepsia, vol 59, iss 1 Epilepsia Epilepsia, Wiley, 2018, 59 (1), pp.37-66. ⟨10.1111/epi.13965⟩ |
| ISSN: | 0013-9580 |
| DOI: | 10.1111/epi.13965 |
| Popis: | The most common forms of acquired epilepsies arise following acute brain insults such as traumatic brain injury, stroke, or central nervous system infections. Treatment is effective for only 60%-70% of patients and remains symptomatic despite decades of effort to develop epilepsy prevention therapies. Recent preclinical efforts are focused on likely primary drivers of epileptogenesis, namely inflammation, neuron loss, plasticity, and circuit reorganization. This review suggests a path to identify neuronal and molecular targets for clinical testing of specific hypotheses about epileptogenesis and its prevention or modification. Acquired human epilepsies with different etiologies share some features with animal models. We identify these commonalities and discuss their relevance to the development of successful epilepsy prevention or disease modification strategies. Risk factors for developing epilepsy that appear common to multiple acute injury etiologies include intracranial bleeding, disruption of the blood-brain barrier, more severe injury, and early seizures within 1 week of injury. In diverse human epilepsies and animal models, seizures appear to propagate within a limbic or thalamocortical/corticocortical network. Common histopathologic features of epilepsy of diverse and mostly focal origin are microglial activation and astrogliosis, heterotopic neurons in the white matter, loss of neurons, and the presence of inflammatory cellular infiltrates. Astrocytes exhibit smaller K+ conductances and lose gap junction coupling in many animal models as well as in sclerotic hippocampi from temporal lobe epilepsy patients. There is increasing evidence that epilepsy can be prevented or aborted in preclinical animal models of acquired epilepsy by interfering with processes that appear common to multiple acute injury etiologies, for example, in post-status epilepticus models of focal epilepsy by transient treatment with a trkB/PLCγ1 inhibitor, isoflurane, or HMGB1 antibodies and by topical administration of adenosine, in the cortical fluid percussion injury model by focal cooling, and in the albumin posttraumatic epilepsy model by losartan. Preclinical studies further highlight the roles of mTOR1 pathways, JAK-STAT3, IL-1R/TLR4 signaling, and other inflammatory pathways in the genesis or modulation of epilepsy after brain injury. The wealth of commonalities, diversity of molecular targets identified preclinically, and likely multidimensional nature of epileptogenesis argue for a combinatorial strategy in prevention therapy. Going forward, the identification of impending epilepsy biomarkers to allow better patient selection, together with better alignment with multisite preclinical trials in animal models, should guide the clinical testing of new hypotheses for epileptogenesis and its prevention. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|