The long-term influences of age at injury on neuroinflammation and neuronal apoptosis following traumatic brain injury in pediatric and adult mice

Objective: The study explores the long-term impacts of traumatic brain injury (TBI) on neuroinflammation and neuronal apoptosis in pediatric and adult mice, focusing on how age at injury influences these processes. Methods: Controlled cortical impacts were used to induce TBI in pediatric (21-25 days old) and adult (8-12 weeks old) C57BL/6 male mice. Neuroinflammation was evaluated by measuring immunoreactivity for allograft inflammatory factor 1 (AIF-1)/ionized calcium-binding adaptor molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP), while apoptosis was assessed using markers such as B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax), Bcl-2, and procaspase-3. Additionally, heat shock protein 70 (HSP70) expression was measured to understand the stress response. Results: Following controlled cortical impacts, pediatric mice exhibited a significant reduction in expression of neuronal nuclei (P<0.001), and significant increases in expression of GFAP (P<0.01) and AIF-1/Iba-1 (P<0.05) at 3 days post-injury (DPI) compared with sham controls. In contrast, adult mice exhibited no significant change in AIF-1/Iba-1 expression and a less pronounced increase in GFAP (P<0.05) at 3 DPI compared with sham controls. A more significant increase in Bax/Bcl-2 ratio at 7 DPI (P<0.01) was seen in pediatric mice, while a weak but significant increase in Bax/Bcl-2 ratio at 7 DPI (P<0.05) was evident in adults. Both age groups showed a significant but transient increase in HSP70 levels at 7 DPI, which normalized by 90 DPI. Conclusion: Pediatric and adult mice exhibited significant time-dependent differences in neuroinflammation and apoptosis following TBI, with pediatric mice showing more intense early responses indicative of age-specific vulnerabilities in post-injury outcomes. Both age groups showed a significant but transient increase in HSP70 expression, suggesting an acute response to stress post-injury. Keywords: Apoptosis; Controlled cortical impact; HSP70 heat-shock proteins; Neuroinflammation; Neuroprotection.