AMPK induces regulatory innate lymphoid cells after traumatic brain injury.

The CNS is regarded as an immunoprivileged organ, evading routine immune surveillance; however, the coordinated development of immune responses profoundly influences outcomes after brain injury. Innate lymphoid cells (ILCs) are cytokine-producing cells that are critical for the initiation, modulation, and resolution of inflammation, but the functional relevance and mechanistic regulation of ILCs are unexplored after acute brain injury. We demonstrate increased proliferation of all ILC subtypes within the meninges for up to 1 year after experimental traumatic brain injury (TBI) while ILCs were present within resected dura and elevated within cerebrospinal fluid (CSF) of moderate-to-severe TBI patients. In line with energetic derangements after TBI, inhibition of the metabolic regulator, AMPK, increased meningeal ILC expansion, whereas AMPK activation suppressed proinflammatory ILC1/ILC3 and increased the frequency of IL-10-expressing ILC2 after TBI. Moreover, intracisternal administration of IL-33 activated AMPK, expanded ILC2, and suppressed ILC1 and ILC3 within the meninges of WT and Rag1-/- mice, but not Rag1-/- IL2rg-/- mice. Taken together, we identify AMPK as a brake on the expansion of proinflammatory, CNS-resident ILCs after brain injury. These findings establish a mechanistic framework whereby immunometabolic modulation of ILCs may direct the specificity, timing, and magnitude of cerebral immunity.

Awakening following cardiac arrest: Determined by the definitions used or the therapies delivered?

AIMS: To investigate patterns of neurologic "awakening" in out-of-hospital cardiac arrest (OHCA) patients using different criteria for prognostication post-arrest. METHODS: Data was collected on 194 OHCA survivors to hospital admission. Patients were assigned to one of two groups based on whether they received therapeutic hypothermia (TH). Three separate criteria were used to assess neurologic "awakening": motor-GCS=6, total-GCS ≥ 9, and CPC=1 or 2. Demographics, arrest characteristics and intensive care events were compared using unpaired t-test, Chi-square or nonparametric Wilcoxon rank-sum test as appropriate. Primary outcome was the time from arrest to neurologic awakening. RESULTS: Of 194 OHCA survivors, TH was implemented in 94 patients (48%). Compared to conventional care patients, hypothermia treated patients were more likely to be younger (58 vs. 69 years, p<0.01),), and have a shockable arrest rhythm (27% vs. 10%, p<0.01). Using the three criteria (m-GCS=6, t-GCS ≥ 9 & CPC=1 or 2), median time to awakening for patients in the hypothermia group versus the conventional therapy group were 6 [4,9] vs. 3 [2,5] days, 3 [3,5] vs. 2 [2,3] days, and 3 [3,6] vs. 2 [2,4] days respectively (all p<0.01) and prognostication using these criteria on day 3 yielded discordant results about which patients achieved awakening. CONCLUSIONS: Patients undergoing therapeutic hypothermia achieve meaningful neurologic "awakening" beyond 72 h post-arrest. Use of different criteria for the assessment of neurologic "awakening" can yield different prognostication predictions which calls for standardization and validation of a single definition of "awakening" by the resuscitation community.