Traumatic brain injury (TBI) is a worldwide medical problem, and currently, there are few therapeutic interventions that can protect the brain and improve functional outcomes in patients. Over the last several decades, experimental studies have investigated the pathophysiology of TBI and tested various pharmacological treatment interventions targeting specific mechanisms of secondary damage. Although many preclinical treatment studies have been encouraging, there remains a lack of successful translation to the clinic and no therapeutic treatments have shown benefit in phase 3 multicenter trials. Therapeutic hypothermia and targeted temperature management protocols over the last several decades have demonstrated successful reduction of secondary injury mechanisms and, in some selective cases, improved outcomes in specific TBI patient populations. However, the benefits of therapeutic hypothermia have not been demonstrated in multicenter randomized trials to significantly improve neurological outcomes. Although the exact reasons underlying the inability to translate therapeutic hypothermia into a larger clinical population are unknown, this failure may reflect the suboptimal use of this potentially powerful therapeutic in potentially treatable severe trauma patients. It is known that multiple factors including patient recruitment, clinical treatment variables, and cooling methodologies are all important in yielding beneficial effects. High-quality multicenter randomized controlled trials that incorporate these factors are required to maximize the benefits of this experimental therapy. This article therefore summarizes several factors that are important in enhancing the beneficial effects of therapeutic hypothermia in TBI. The current failures of hypothermic TBI clinical trials in terms of clinical protocol design, patient section, and other considerations are discussed and future directions are emphasized.

Alzheimer's disease (AD) is one of the most common and devastating aging-related neurodegenerative diseases. Besides the well-known role of chemokines and their receptors in the immune system, they are widely expressed in the nervous system, where they play roles in the regulation of cell migration and neurotransmission. The chemokine CXC motif receptor 4 (CXCR4) is evolutionarily highly conserved seven-transmembrane G-protein-coupled receptors (GPCRs). It has been demonstrated that CXCL12/CXCR4 signaling pathway involved in the pathologic process of AD. In this review, we demonstrated the GPCR family proteins and summarized the relationship between CXCR4 and GPCR, CXCR4 and AD. The review aimed to provide the novel insight of CXCR4 into the early prevention of mild cognitive impairment and in the diagnosis and treatment of AD.

BACKGROUND: Limb remote ischemic conditioning (LRIC) and atorvastatin (AtS) both provide neuroprotection in stroke. We evaluated the enhanced neuroprotective effect of combining these two treatments in preventing ischemia/reperfusion (I/R)-induced cerebral injury in a rat model and investigated the corresponding molecular mechanisms. MATERIALS AND METHODS: Transient cerebral ischemia was induced in Sprague–Dawley male rats by middle cerebral artery occlusion (MCAO) for 90 min followed by reperfusion (I/R). Rats were divided into 5 groups, sham, I/R, I/R + AtS, I/R + LRIC and I/R + AtS + LRIC. Pretreatment with LRIC and/or AtS for 14 days before MCAO surgery. Infarct volume, neurological score, Western blot, immuno-histochemical analyses were performed. RESULTS: The combination of LRIC plus AtS pretreatment decreased infarct volume and inhibited neuronal apoptosis. Combination treatment achieved stronger neuroprotection than monotherapy with LRIC or AtS. These therapies reduced reactive oxygen species production in the peri-ischemia region, associated with significantly increased expression and activation of superoxide dismutase 1, hemeoxygenase 1 and nuclear factor erythroid 2-related factor 2. CONCLUSIONS: Both LRIC and AtS + LRIC treatments conferred neuroprotection in ischemic stroke by reducing brain oxidative stress. AtS plus LRIC is an attractive translational research option due to its ease of use, tolerability, economical, and tremendous neuroprotective potential in stroke.

BACKGROUND: Revascularization surgery has been the standard treatment to prevent ischemic stroke in pediatric Moyamoya disease (MMD) patients with ischemic symptoms. However, perioperative complications, such as hyperperfusion syndrome, new infarct on imaging, or ischemic stroke, are inevitable. Remote ischemic conditioning (RIC) is a noninvasive and easy-to-use neuroprotective strategy, and it has potential effects on preventing hyperperfusion syndrome and ischemic infarction. AIMS: The aim of this study is to investigate the safety and efficacy of RIC in pediatric MMD patients undergoing revascularization surgery. METHOD: A total of 60 pediatric MMD patients with one or more ischemic symptoms will be recruited and allocated in 1:1 ratio to the RIC group and sham group, respectively. Both RIC and sham RIC will be performed twice daily for 7 consecutive days before revascularization surgery with different cuff pressures during the ischemia period (50 mmHg over-systolic blood pressure and 30 mmHg). Single photon emission computed tomography will be performed within 7 days preoperatively and 3 months postoperatively, respectively, to evaluate the cerebral perfusion status. Other outcomes, including safety, plasma biomarker, functional outcome, and the incidence of infarction and its size, will also be evaluated. CONCLUSION: This study will provide insights into the preliminary proof of principle, safety, and efficacy of RIC in pediatric MMD patients undergoing revascularization surgery therapy, and this data will provide parameters for future larger scale clinical trials if efficacious.

OBJECTIVE: Mild hypothermia has a protective effect on ischemic stroke, but the mechanisms remain elusive. Here, we investigated microRNA (miRNA) profiles and the specific role of miRNAs in ischemic stroke treated with mild hypothermia. MATERIALS AND METHODS: Male adult Sprague Dawley rats were subjected to focal transient cerebral ischemia. Mild hypothermia was induced by applying ice packs around the neck and head of the animals. miRNAs expression profiles were detected in ischemic stroke treated with mild therapeutic hypothermia through miRNA chips. Reverse transcription-polymerase chain reaction (RT-PCR) was used to verify the change of miRNA array. Western blot and adenosine triphosphate (ATP) assay kits were used to detect the changes of protein expression and ATP levels, respectively. miR-15b mimic and its control were injected into the right lateral ventricle 60 min before the induction of ischemia. RESULTS: The results showed that mild hypothermia affected miRNAs profiles expression. We verified the expression of miR-15b and miR-598-3p by miRNA RT-PCR. miR-15b mimic inhibited the expression of its target, ADP ribosylation factor-like 2 (Arl2) protein, and decreased ATP levels in PC12 cells. Compared with the control, miR-15b mimic increased the infarct volume and aggravated the neurological function under normothermia or hypothermia treatment. Furthermore, the expression of Arl2 was decreased in the miR-15b mimic group under normothermia or hypothermia treatment. CONCLUSIONS: Mild therapeutic hypothermia affected miRNA profiles and protected against cerebral ischemia/reperfusion by inhibiting miR-15b expression in rats. miR-15b may be a potential target for therapeutic intervention in stroke.

Cerebral venous sinus thrombosis (CVST) is an uncommon, life-threatening condition with a variable clinical presentation that makes it a challenge of diagnosis. A 39-year-old male patient presented to the hospital with complete loss of conscious and admitted to Medical Intensive Care Unit for investigation without any obvious history that was difficult for diagnosis. In this case, the patient presented with coma that is a rare presentation of CVST with no obvious clinical history and he was male patient that means he is free of all gender-specific risk factors of CVST. The brain computed tomography (CT) scan showed hypodense lesion in the left upper parietal region with no hemorrhage. The lesion was low-signal intensity (SI) on T1WIs and high SI on T2WIs and restricted on diffusion-weighted images like arterial infarctions, but magnetic resonance angiography (MRA) was normal that excluded arterial infarction. Gadolinium-enhanced MR venography (MRV) showed the filling defect of CVST. CVST can be present by a mysterious clinical presentation that makes it as a challenge of diagnosis even by medical imaging by CT and MR imaging (MRI). A combination of MRI and MRV is the best, noninvasive, and nonionizing imaging modality for the diagnosis of CVST.