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.

Objective
Hypoxic ischemia (HI) is a secondary insult that can cause fatal neurologic outcomes after traumatic brain injury (TBI), ranging from mild cognitive deficits to persistent vegetative states. We here aimed to unravel the underlying pathological mechanisms of HI injury in a TBI mouse model.
Methods
Neurobehavior, neuroinflammation, and oxidative stress were assessed in a mouse model of controlled cortical impact (CCI) injury followed by HI. Mice underwent CCI alone, CCI followed by HI, HI alone, or sham operation. HI was induced by one-vessel carotid ligation with 1 hour of 8% oxygen in nitrogen. Learning and memory were assessed using the novel object recognition test, contextual and cued fear conditioning, and Barnes maze test. Brain cytokine production and oxidative stress-related components were measured.
Results
Compared to TBI-only animals, TBI followed by HI mice exhibited significantly poorer survival and health scores, spatial learning and memory in the Barnes maze test, discrimination memory in the novel object recognition test, and fear memory following contextual and cued fear conditioning. Malondialdehyde levels were significantly lower, whereas glutathione peroxidase activity was significantly higher in TBI followed by HI mice compared to TBI-only and sham counterparts, respectively. Interleukin-6 levels were significantly higher in TBI followed by HI mice compared to both TBI-only and sham animals.
Conclusion
Post-traumatic HI aggravated deficits in spatial, fear, and discrimination memory in an experimental TBI mouse model. Our results suggest that increased neuroinflammation and oxidative stress contribute to HI-induced neurobehavioral impairments after TBI.