Transplanted interneurons improve memory precision after traumatic brain injury.
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ABSTRACT:
SUBMITTER: Zhu B
PROVIDER: S-EPMC6856380 | biostudies-literature | 2019 Nov
REPOSITORIES: biostudies-literature
Publications
Transplanted interneurons improve memory precision after traumatic brain injury.
Zhu Bingyao B Eom Jisu J Hunt Robert F RF
Nature communications 20191114 1
Repair of the traumatically injured brain has been envisioned for decades, but regenerating new neurons at the site of brain injury has been challenging. We show GABAergic progenitors, derived from the embryonic medial ganglionic eminence, migrate long distances following transplantation into the hippocampus of adult mice with traumatic brain injury, functionally integrate as mature inhibitory interneurons and restore post-traumatic decreases in synaptic inhibition. Grafted animals had improveme ...[more]
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Project description:IntroductionPrevious research indicates disruption of learning and memory in children who have experienced traumatic brain injury (TBI).ObjectiveThis research evaluates the impact of pediatric TBI on volumetric differences along the long axis of the hippocampus, a region of the brain that is critical for explicit memory.MethodsStructural brain data and behavioral measures were collected 6 weeks following TBI or extracranial injury (EI), in children aged 8-15 years and from a group of age matched typically developing controls (TDC). Total hippocampal volume and hippocampal subregion volumes corresponding to hippocampal head, body, and tail were compared across groups and were examined in relation to verbal and visual memory.ResultsGroup differences were evident such that hippocampal body volume was found to be smaller for TBI and EI groups compared to the TDC group. Analysis restricted to the TBI group indicated that hippocampal head volume was associated with severity of injury. The relation between severity of injury and hippocampal head volume is particularly important considering results from our investigation of hippocampal volume-to-memory performance relations indicating positive correlations between hippocampal head volume and performance on memory measures for both the TBI group and the TDC group. Significant negative correlations between hippocampal body volume and memory were evident for the TBI group but not EI or TDC groups. Correlations between memory performance and hippocampal tail volume were not significant for the TBI or TDC groups, although for the EI group, a positive correlation was found between hippocampal tail volume and memory.ConclusionTogether these results underscore an important relation between hippocampal structure and memory function during the subacute stage of recovery from pediatric TBI.
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Project description:BackgroundTraumatic brain injury (TBI) is a complex disorder that is traditionally stratified based on clinical signs and symptoms. Recent imaging and molecular biomarker innovations provide unprecedented opportunities for improved TBI precision medicine, incorporating patho-anatomical and molecular mechanisms. Complete integration of these diverse data for TBI diagnosis and patient stratification remains an unmet challenge.Methods and findingsThe Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Pilot multicenter study enrolled 586 acute TBI patients and collected diverse common data elements (TBI-CDEs) across the study population, including imaging, genetics, and clinical outcomes. We then applied topology-based data-driven discovery to identify natural subgroups of patients, based on the TBI-CDEs collected. Our hypothesis was two-fold: 1) A machine learning tool known as topological data analysis (TDA) would reveal data-driven patterns in patient outcomes to identify candidate biomarkers of recovery, and 2) TDA-identified biomarkers would significantly predict patient outcome recovery after TBI using more traditional methods of univariate statistical tests. TDA algorithms organized and mapped the data of TBI patients in multidimensional space, identifying a subset of mild TBI patients with a specific multivariate phenotype associated with unfavorable outcome at 3 and 6 months after injury. Further analyses revealed that this patient subset had high rates of post-traumatic stress disorder (PTSD), and enrichment in several distinct genetic polymorphisms associated with cellular responses to stress and DNA damage (PARP1), and in striatal dopamine processing (ANKK1, COMT, DRD2).ConclusionsTDA identified a unique diagnostic subgroup of patients with unfavorable outcome after mild TBI that were significantly predicted by the presence of specific genetic polymorphisms. Machine learning methods such as TDA may provide a robust method for patient stratification and treatment planning targeting identified biomarkers in future clinical trials in TBI patients.Trial registrationClinicalTrials.gov Identifier NCT01565551.
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