Genetic underpinnings of cerebral edema in acute brain injury: an opportunity for pathway discovery
| Autor: | Elayna Kirsch, Natalia Szejko, Guido J. Falcone |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Apolipoprotein E Traumatic brain injury Brain Edema Neuroimaging Bioinformatics Article Cerebral edema Brain Ischemia 03 medical and health sciences 0302 clinical medicine Edema medicine Animals Humans Stroke Intracerebral hemorrhage Aquaporin 4 business.industry General Neuroscience medicine.disease 030104 developmental biology Brain Injuries Biomarker (medicine) medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | Neurosci Lett |
| ISSN: | 1872-7972 |
| Popis: | Cerebral edema constitutes an important contributor to secondary injury in acute brain injury. The quantification of cerebral edema in neuroimaging, a well-established biomarker of secondary brain injury, represents a useful intermediate phenotype to study edema formation. Population genetics provides powerful tools to identify novel susceptibility genes, biological pathways and therapeutic targets related to brain edema formation. Here, we provide an overview of the pathogenesis of cerebral edema, introduce relevant genetic methods to study this process, and discuss the ongoing research on the genetic underpinnings of edema formation in acute brain injury. The epsilon 2 and 4 variants within the Apolipoprotein E (APOE) gene are associated with worse outcome after traumatic brain injury and intracerebral hemorrhage, and recent studies link these polymorphisms to inflammatory processes that lead to blood-brain barrier disruption and vasogenic edema. For the Haptoglobin gene (HP), the Hp 2−2 genotype associates with worse outcome after acute brain injury, whereas the haptoglobin Hp 1−1 genotype correlates with increased edema in the early phases of intracerebral hemorrhage. Another important protein in cerebral edema is aquaporin 4, coded by the AQP4 gene. AQP4 mutations contribute to the formation of cytotoxic edema, and further genetic research is necessary to help elucidate the mediating mechanism. Findings supporting the target genes outlined above require replication in larger samples and evaluation in non-white populations. These next steps will be significantly facilitated by the rapid changes observed in the field of population genetics, including large international collaborations, open access to genetic data, and significant reductions in the cost of genotyping technologies. |
| Databáze: | OpenAIRE |
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