Journal of neurotrauma
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Journal of neurotrauma · Jul 2021
Autoregulatory or fixed cerebral perfusion pressure targets in traumatic brain injury - what is better in an energy metabolic perspective?
Current guidelines in traumatic brain injury (TBI) recommend a cerebral perfusion pressure (CPP) within the fixed interval of 60-70 mm Hg. However, the autoregulatory, optimal CPP target (CPPopt) might yield better cerebral blood flow (CBF) regulation. In this study, we investigated fixed versus autoregulatory CPP targets in relation to cerebral energy metabolism and clinical outcome after TBI. ⋯ Higher GMT (%) CPP within 60-70 mm Hg correlated with lower cerebral glucose on days 2-10 and higher LPR on days 6-10, but predicted favorable clinical outcome. Higher GMT (%) CPP >70 mm Hg had the opposite associations; that is, with higher cerebral glucose and lower LPR, but unfavorable clinical outcome. Autoregulatory CPP targets may be beneficial, because patients with CPP values close to the optimal CPP had both better cerebral energy metabolism and better clinical outcome, but this needs to be evaluated in randomized trials.
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Journal of neurotrauma · Jul 2021
Impaired glutamate receptor function underlies early activity loss of ipsilesional motor cortex following closed-head mild traumatic brain injury.
Although mild traumatic brain injury (mTBI) accounts for the majority of TBI patients, the effects and cellular and molecular mechanisms of mTBI on cortical neural circuits are still not well understood. Given the transient and non-specific functional deficits after mTBI, it is important to understand whether mTBI causes functional deficits of the brain and the underlying mechanism, particularly during the early stage after injury. Here, we used in vivo optogenetic motor mapping to determine longitudinal changes in cortical motor map and in vitro calcium imaging to study how changes in cortical excitability and calcium signals may contribute to the motor deficits in a closed-head mTBI model. ⋯ Imaging of calcium transients evoked by glutamate uncaging revealed reduced response amplitudes and longer duration in 2, 12, and 24 h after mTBI. Higher percentages of neurons of the injured cortex had a longer latency period after uncaging than that of the uninjured neurons. The results suggest that impaired glutamate neurotransmission contributes to functional deficits of the motor cortex in vivo, which supports enhancing glutamate neurotransmission as a potential therapeutic approach for the treatment of mTBI.
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Journal of neurotrauma · Jul 2021
Chemokine receptors CCR5 and CXCR4 are new therapeutic targets for brain recovery following Traumatic Brain Injury.
Recently, chemokine receptor CC chemokine receptor 5 (CCR5) was found to be a negative modulator of learning and memory. Its inhibition improved outcome after stroke and traumatic brain injury (TBI). To better understand its role after TBI and establish therapeutic strategies, we investigated the effect of reduced CCR5 signaling as a neuroprotective strategy and of the temporal changes of CCR5 expression after TBI in different brain cell types. ⋯ The ccr5 shRNA also reduced astrocytosis in the lesioned and sublesioned cortex. FACS analysis revealed increased cortical CCR5 and CXCR4 expression in CD11b-positive cells, astrocytes, and neurons, which was most evident in cells expressing both receptors, at 3 and 11 days post-injury. The lowest levels of phosphorylated NR1 and phosphorylated CREB were found at day 3 post-injury, suggesting that this is the critical time point for therapeutic intervention.