Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
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N-acylethanolamines (NAEs) are endogenous bioactive lipids reported to exert anti-inflammatory and neuroprotective effects mediated by cannabinoid receptors and peroxisome proliferator-activated receptors (PPARs), among others. Therefore, interfering with NAE signaling could be a promising strategy to decrease inflammation in neurological disorders such as multiple sclerosis (MS). Fatty acid amide hydrolase (FAAH) and N-acylethanolamine-hydrolyzing acid amidase (NAAA) are key modulators of NAE levels. ⋯ Moreover, the inhibition of both NAAA and FAAH, using a dual-inhibitor or the co-administration of NAAA and FAAH inhibitors, did not show an added value compared to NAAA inhibition. Furthermore, our data suggest an important role of decreased activation of astrocytes and microglia in the effects of NAAA inhibition on EAE, while NAAA inhibition did not affect T cell recall. This work highlights the beneficial effects of NAAA inhibition in the context of central nervous system inflammation and suggests that the simultaneous inhibition of NAAA and FAAH has no additional beneficial effect in EAE.
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Activated microglia can suppress neurite outgrowth and synapse recovery in the acute stage following traumatic brain injury (TBI). However, the underlying mechanism has not been clearly elucidated. Exosomes derived from microglia have been reported to play a critical role in microglia-neuron interaction in healthy and pathological brains. ⋯ Moreover, motor coordination in miR-5121 overexpressed exosomes treated mice was significantly improved after FPI. Following mechanistic study demonstrated that miR-5121 might promote neurite outgrowth and synapse recovery by directly targeting RGMa. In conclusion, our finding revealed a novel exosome-mediated mechanism of microglia-neuron interaction that suppressed neurite outgrowth and synapse recovery of neurons following TBI.
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Three decades ago, continuous positive airway pressure (CPAP) was introduced to treat obstructive sleep apnea (OSA). Shortly after, bilevel positive airway pressure devices (BPAP) that independently adjusted inspiratory and expiratory positive airway pressure were developed to treat complex sleep-related breathing disorders unresponsive to CPAP. Based on the bilevel positive airway pressure platform (hardware) governed by propriety algorithms (software), advanced modes of noninvasive ventilation (NIV) were developed to address complex cardiorespiratory pathophysiology beyond OSA. This review summarizes key aspects of different bilevel PAP therapies (BPAP with/without backup rate, adaptive servoventilation, and volume-assured pressure support) to treat common sleep-related hypoventilation disorders, treatment-emergent central sleep apnea, and central sleep apnea syndromes.
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Chemotherapy-induced peripheral neuropathic pain (CIPNP) often occurs in cancer patients treated with antineoplastic drugs. Therapeutic management of CIPNP is very limited, at least in part due to the largely unknown mechanisms that underlie CIPNP genesis. Here, we showed that systemic administration of the chemotherapeutic drug paclitaxel significantly and time-dependently increased the levels of cyclic AMP response element-binding protein (CREB) in dorsal root ganglion (DRG) neurons. ⋯ CREB overexpression also elevated the expression of DNMT3a in in vivo and in vitro DRG neurons of naïve mice. Given that DNMT3a is an endogenous instigator of CIPNP and that CREB co-expresses with DNMT3a in DRG neurons, CREB may be a key player in CIPNP through transcriptional activation of the Dnmt3a gene in primary sensory neurons. CREB is thus a likely potential target for the therapeutic management of this disorder.
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Randomized Controlled Trial
One-Day Acceptance and Commitment Therapy Compared to Support for Depressed Migraine Patients: a Randomized Clinical Trial.
In patients with migraine, depression is associated with poorer medical prognosis, decreased quality of life, and increased risk of suicidality and disability; yet, behavioral interventions have rarely been investigated. The current study compared the efficacy of two 1-day (5- to 6-h) interventions for co-occurring migraine and depression: (1) acceptance and commitment therapy plus migraine education (ACT-ED), and (2) support plus migraine education (S-ED). One hundred and thirty-six patients with comorbid depression and migraine were randomized to a treatment. ⋯ A 1-day (5- to 6-h) ACT workshop can deliver substantial and lasting benefits to depressed migraineurs, over and above those provided by group support and education. This approach is an attractive alternative to weekly psychotherapy. Clinicaltrials.gov # NCT02108678.