TBI Biomarker Improvements Following Rodent Decompressive Craniectomy and Motor Outcome Validation of Early Cranioplasty

Abstract

Background

Decompressive craniectomy (DC) is a venerable clinical tool to manage moderate-to-severe traumatic brain injury (TBI). The utility of recently approved neuroinflammatory biomarkers glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) is unclear in DC patients as does the timing of cranioplasty to repair/restore the missing cranial bone. We hypothesize that DC diminishes acute neuroinflammatory biomarkers GFAP and UCH-L1 and that early cranioplasty improves motor recovery following DC in moderate-to-severe TBI.

Methods

A rodent TBI paradigm utilized a “hit-and-run” closed cortical impact to induce moderate-to-severe trauma. GFAP and UCH-L1 were quantified in CD1 mice (ELISA) in sham, TBI, and TBI-DC. Concurrently, Long-Evans rats received early or delayed alloplastic cranioplasty, with beam walk to assess motor proficiency. A 2-way ANOVA with Dunnett's post hoc determined group-level differences.

Results

GFAP and UCH-L1 were elevated in TBI at post-TBI day 1 (GFAP: P = .0233; UCH-L1: P = .0005) and partially elevated in TBI-DC (GFAP: P = .0603; UCH-L1: P = .0326). By day 7, biomarker levels converged (P > .05), indicating acute neuroinflammation resolution. Early cranioplasty maintained near-sham motor performance at day 4 (P = .9925). Absence of cranioplasty (TBI-DC) produced persistent deficits (day 4: P = .0319; day 11: P = .0069; day 18: P = .0112). Late cranioplasty yielded improvement, achieving near-sham results by day 11 or post-cranioplasty day 5 (P = .9166).

Conclusions

In this moderate-to-severe TBI model, DC significantly mitigates astroglial and neuronal biomarker expression. Timely cranioplasty further augments motor recovery, underscoring its relevance for optimizing neurological convalescence following decompressive surgery in acute TBI management.