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Astrocyte-microglial interaction plays a crucial role in brain injury-associated neuroinflammation. Our previous data illustrated that astrocytes secrete microRNA, leading to anti-inflammatory effects on microglia. Long non-codingRNAs participate in neuroinflammation regulation post traumatic brain injury. However, the effect of astrocytes on microglial phenotype via long non-codingRNAs and the underlying molecular mechanisms remain elusive. We used long non-codingRNA sequencing on murine astrocytes and found that exosomal long non-codingRNA 4933431K23Rik attenuated traumatic brain injury-induced microglial activation in vitroand in vivoand ameliorated cognitive function deficiency. Furthermore, microRNA and messengerRNA sequencing together with binding prediction illustrated that exosomal long non-codingRNA 4933431K23Rik up-regulates E2F7 and TFAP2C expression by sponging miR-10a-5p. Additionally, E2F7 and TFAP2C, as transcription factors, regulated microglial Smad7 expression. Using Cx3cr1-Smad7 overexpression of adeno-associated virus, microglia specifically overexpressed Smad7 in the attenuation of neuroinflammation, resulting in less cognitive deficiency post traumatic brain injury. Mechanically, overexpressed Smad7 physically binds to IκBα and inhibits its ubiquitination, preventing NF-κB signaling activation. The Smad7 activator asiaticoside alleviates neuroinflammation and protects neuronal function in traumatic brain injury mice. This study revealed that an exosomal long non-codingRNA from astrocytes attenuates microglial activation post traumatic brain injury by up-regulating Smad7, providing a potential therapeutic target.

Despite the improving imaging techniques, it remains challenging to predict the outcome early after transient cerebral ischemia. The aim of this study was thus to identify early metabolic biomarkers for outcome prediction.

The effect of deep barbiturate anesthesia on brain glucose transport, TCA cycle flux, and aspartate, glutamate, and glutamine metabolism was assessed in the rat brain in vivousing 13C nuclear magnetic resonance spectroscopy at 9.4 T in conjunction with [1-13C] glucose infusions. Brain glucose concentrations were elevated, consistent with a twofold reduced cerebral metabolic rate for glucose (CMRglc) compared with light α-chloralose anesthesia. Using a mathematical model of neurotransmitter metabolism, several metabolic reaction rates were extracted from the rate of label incorporation. Total oxidative glucose metabolism, CMRglc(ox), was 0.33 ± 0.03 μmol·g−1· min−1. The neuronal TCA cycle rate was similar to that in the glia, 0.35 ± 0.03 μmol · g−1· min−1and 0.26 ± 0.06 μmol · g−1· min−1, respectively, suggesting that neuronal energy metabolism was mainly affected. The rate of pyruvate carboxylation was 0.03 ± 0.01 μmol·g−1· min−1. The exchange rate between cytosolic glutamate and mitochondrial 2-oxoglutarate, Vx, was equal to the rate of neuronal pyruvate dehydrogenase flux. This indicates that Vxis coupled to CMRglc(ox), implying that the malate-aspartate shuttle is the major mechanism that facilitates label exchange across the inner mitochondrial membrane. The apparent rate of glutamatergic neurotransmission, VNT, was 0.04 ± 0.01 μmol·g−1· min−1, consistent with strong reductions in electrical activity. However, the rates of cerebral oxidative glucose metabolism and glutamatergic neurotransmission, CMRglc(ox)/VNT, did not correlate with a 1:1 stoichiometry.