Medical Student Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA Pittsburgh, PA, US
Introduction: Hemoglobinopathy affects over 300 million individuals globally. Like traumatic brain injury (TBI), sickle cell disease (SCD) and thalassemia show chronic hypoxia, thromboembolism risk, and vascular inflammation. Understanding pathological exacerbation of post-injury inflammation can provide insight into hemoglobinopathy as a ubiquitous potential modifier of TBI progression and severity.
Methods: Six Berkeley (SCD) and six C57BL/6J (WT) controls aged 12-18 weeks were split into two cohorts (n=3/group) for controlled cortical impact (CCI) and control (sham). Plasma samples were collected at baseline, 24 hours, and 72 hours post-injury/sham. A multiplex assay quantified inflammatory markers. Coronal brain sections were stained with Prussian Blue for iron deposition. Two-way ANOVAs and post-hoc t-tests identified significant group mean differences in inflammatory marker concentrations. Tukey’s HSD test was used to correct for multiple comparisons.
Results: One SCD-CCI mice died at 24 hours while another was euthanized at 48 hours in accordance with health criteria. IL-10 plasma concentrations at baseline were significantly higher in SCD mice (mean [SEM]: 2.559 [0.150] pg/mL; p=0.0008) compared to WT mice (1.337 [0.178] pg/mL). Conversely, IL-1b levels 24 hours post-injury/sham were significantly lower in SCD mice (33.18 [8.923] pg/mL; p=0.0320) in comparison to WT mice (105.80 [30.48] pg/mL). Similarly, IFN-y concentrations in SCD mice 24 hours post-CCI/sham (0.163 [0.0293] pg/mL) were significantly lower compared to WT mice (0.308 [0.0394] pg/mL; p=0.0264). The two SCD-CCI mice removed from the study showed the highest levels of IL-10 (36.255 and 10.021 pg/mL) and lowest levels of IL-1b (7.179 and 10.482 pg/mL) at 24 hours post-injury/sham across all animals. Prussian Blue staining suggested increased perivascular iron deposition in the surviving SCD-CCI mouse.
Conclusion : This pilot study suggests increased TBI susceptibility, perivascular hemorrhage and altered inflammatory response following TBI in SCD, with elevated anti-inflammatory IL-10 and dampened pro-inflammatory IL-1b and IFN-y. Our ongoing work is further characterizing interactions between TBI and hemoglobinopathy.
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