Background: Severe brain injury significantly influences immune responses. However, the levels at which such influence occur and the involvement of neurogenic pathways are not well defined.
Methods: 39 eligible patients with supratentorial ICH within 24 hours of onset and 20 matched healthy controls were enrolled. Hematoma sizes at admission were calculated via computed tomography (CT). Perihematomal edema (PHE) and spleen volume at day 3 and 14 were measured via T2-weighted magnetic resonance imaging (MRI), respectively. Tissue diffusion and capillary perfusion of spleen were quantified by Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) with 9 b values. Peripheral lymphocyte subsets were quantified by flow cytometry. Neurotransmitters and stress hormone were detected by enzyme-linked immunosorbent assay (ELISA). Association of splenic and cellular alterations with progression of PHE and the outcomes of ICH patients were analyzed. Mechanisms governing the spleen and lymphocyte alterations after ICH were investigated in mouse models of ICH.
Results: Average spleen shrinkage of 37ml accompanied by splenic capillary perfusion increase occurred in ICH patients at day 3 after disease onset. The magnitude of spleen shrinkage was associated with hematoma size upon admission. Concurrently, patients with severe spleen shrinkage (> 37ml) had less progression of PHE. Lymphopenia was observed in ICH patients after ictus and persisted up to 14 day, which was not parallel with spleen alteration. Patients with infections exhibited poorer functional outcome and significant T and NK cell deficiency. In ICH models, signals derived from adrenergic and hypothalamus-pituitary-adrenal (HPA) axis activation contributed to loss of white blood cells in the white pulp.
Conclusions: Spleen shrinkage and lymphopenia reflect the impact of ICH on the immune system at the organ and cellular levels, such impacts are derived from coordinated action of sympathetic innervation and HPA axis. The magnitude of spleen shrinkage might be associative with the progression of PHE and clinical outcome of ICH patients. Additionally specific cellular immunity deficiency was associated with increased infection risk in patients.