Background and Purpose:
The ability to predict ischemic stroke outcomes in the first day of admission could be vital for patient counseling, rehabilitation, and care planning. The Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC; clinicaltrials.gov NCT03153683) collects blood samples distal and proximal to the intracranial thrombus during mechanical thrombectomy. These samples are a novel resource in evaluating acute gene expression changes at the time of ischemic stroke. The purpose of this study was to identify inflammatory genes and patient demographics that are predictive of stroke outcomes (infarct and/or edema volume) in acute ischemic stroke patients.
Methods:
The BACTRAC study is a non-probability, convenience sampling of subjects (≥ 18 year olds) treated with mechanical thrombectomy for emergent large vessel occlusion. We evaluated relative concentrations of mRNA for gene expression in 84 inflammatory molecules in static blood distal and proximal to the intracranial thrombus from adults who underwent thrombectomy. We employed a machine learning method, Random Forest, utilizing the first set of enrolled subjects, to predict which inflammatory genes and patient demographics were important features for infarct and edema volumes.
Results:
We analyzed the first 28 subjects (age = 66 ± 15.48, 11 males) in the BACTRAC registry. Results from machine learning analyses demonstrate that the genes CCR4, IFNA2, IL9, CXCL3, Age, DM, IL7, CCL4, BMI, IL5, CCR3, TNF, and IL27 predict infarct volume. The genes IFNA2, IL5, CCL11, IL17C, CCR4, IL9, IL7, CCR3, IL27, DM, and CSF2 predict edema volume. There is an intersection of genes CCR4, IFNA2, IL9, IL7, IL5, CCR3 to both infarct and edema volumes. Overall, these genes depicts a microenvironment for chemoattraction and proliferation of autoimmune cells, particularly Th2 cells and neutrophils.
Conclusions:
Machine learning algorithms can be employed to develop predictive biomarker signatures for stroke outcomes in ischemic stroke patients, particularly in regard to identifying acute gene expression changes that occur during stroke.
Therapeutically Targeting Neuroinflammation and Microglia after Acute Ischemic Stroke