Secondary hypoxic ischemia alters neurobehavioral outcomes, neuroinflammation, and oxidative stress in mice exposed to controlled cortical impact.

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.

Relationships between serum levels of lactate dehydrogenase and neurological outcomes of patients who underwent targeted temperature management after out-of-hospital cardiac arrest.

ABSTRACT: This study aimed to evaluate times for measuring serum lactate dehydrogenase levels (SLLs) to predict neurological prognosis among out-of-hospital cardiac arrest (OHCA) survivors.This retrospective study examined patients who experienced OHCA treated with targeted temperature management (TTM). The SLLs were evaluated at the return of spontaneous circulation (ROSC) and at 24, 48, and 72 hours later. Neurological outcomes after 3 months were evaluated for relationships with the SLL measurement times.A total of 95 comatose patients with OHCA were treated using TTM. Seventy three patients were considered eligible, including 31 patients (42%) who experienced good neurological outcomes. There were significant differences between the good and poor outcome groups at most time points (P < .001), except for ROSC (P = .06). The ROSC measurement had a lower area under the receiver operating characteristic curve (AUC: 0.631, 95% confidence interval [CI]: 0.502-0.761) than at 48 hours (AUC: 0.830, 95% CI: 0.736-0.924), at 24 hours (AUC: 0.786, 95% CI: 0.681-0.892), and at 72 hours (AUC: 0.821, 95% CI: 0.724-0.919).A higher SLL seemingly predicted poor neurological outcomes, with good prognostic values at 48 hours and 72 hours. Prospective studies should be conducted to confirm these results.