The Long-term influences of Age-At-Injury on Neuroinflammation and neuronal Apoptosis following Traumatic Brain Injury in Pediatric and Adulthood Mice.

Abstract

Objective: The study aims to investigate the long-term impacts of traumatic brain injury (TBI) on neuroinflammation and neuronal apoptosis in pediatric and adult mice, specifically focusing on how age-at-injury influences these processes.

Methods: Controlled cortical impact (CCI) was used to induce TBI in pediatric (21-25 days old) and adult (8-12 weeks old) C57Bl/6 male mice. Neuroinflammation was evaluated through immunoreactivity for Iba-1 and GFAP, while apoptosis was assessed using markers such as Bax, Bcl- 2, and pro-caspase-3. Additionally, HSP70 expression was measured to understand the stress response.

Results: Following CCI, pediatric mice exhibited a significant reduction in NeuN expression(p < 0.001), significant increase in GFAP (p < 0.01) and AIF-1/Iba1 expression (p < 0.05) at 3 dpi compared to sham controls. In contrast, adult mice exhibited no significant change in AIF-1/Iba1 expression and a less pronounced increase in GFAP (p < 0.05) at 3 dpi compared to sham controls. Pediatric mice demonstrated a more significant increase in Bax/Bcl-2 ratio at 7 dpi (p < 0.01), While adult mice a little weak significant increase in Bax/Bcl-2 ratio at 7 dpi (p < 0.05). Both age groups showed a significant but transient increase in HSP70 levels at 7 dpi, which normalized by 90 dpi.

Conclusions: Pediatric and adult mice exhibited significant time-dependent differences in neuroinflammation and apoptosis following TBI, with pediatric mice showing more intense early responses, highlighting age-specific vulnerabilities in post-injury outcomes. Both age groups showed a significant but transient increase in HSP70 expression, suggesting an acute stress response postinjury.