MEC17-induced α-tubulin acetylation restores mitochondrial transport function and alleviates axonal injury after intracerebral hemorrhage in mice.

Injury to long axonal projections is a central pathological feature at the early phase of intracerebral hemorrhage (ICH). It has been reported to contribute to persistent functional disability following ICH. However, the molecular mechanisms that drive axonal degeneration remain unclear. Autologous blood was injected into the striatum to mimic the pathology of ICH. Observed significant swollen axons with characteristic retraction bulbs were found around the striatal hematoma at 24 h after ICH. Electronic microscopic examination revealed highly disorganized microtubule and swollen mitochondria in the retraction bulbs. MEC17 is a specific α-tubulin acetyltransferase, ablation of acetylated α-tubulin in MEC17-/- mice aggravated axonal injury, axonal transport mitochondria dysfunction, and motor dysfunction. In contrast, treatment with tubastatin A (TubA), which promotes microtubule acetylation, significantly alleviated axonal injury and protected the integrity of the corticospinal tract and fine motor function after ICH. Moreover, results showed that 41% mitochondria were preferentially bundled to the acetylated α-tubulin in identifiable axons and dendrites in primary neurons. This impaired axonal transport of mitochondria in primary neurons of MEC17-/- mice. Given that opening of mitochondrial permeability transition pore (mPTP) induces mitochondrial dysfunction and impairs ATP supply thereby promoting axonal injury, we enhanced the availability of acetylated α-tubulin using TubA and inhibited mPTP opening with cyclosporin A. The results indicated that this combined treatment synergistically protected corticospinal tract integrity and promoted fine motor control recovery. These findings reveal key intracellular mechanisms that drive axonal degeneration after ICH and highlight the need to target multiple factors and respective regulatory mechanisms as an effective approach to prevent axonal degeneration and motor dysfunction after ICH.

Evaluation of Prognosis of Coma Patients With Acute Brain Injury by Electroencephalogram Bispectral Index Monitoring.

BACKGROUND: The high mortality rate of comatose patients with traumatic brain injury is a prominent public health issue that negatively impacts patients and their families. Objective, reliable tools are needed to guide treatment decisions and prioritize resources. OBJECTIVE: This study aimed to evaluate the prognostic value of the bispectral index (BIS) in comatose patients with severe brain injury. METHODS: This was a retrospective cohort study of 84 patients with severe brain injury and Glasgow Coma Scale (GCS) scores of 8 and less treated from January 2015 to June 2017. Sedatives were withheld at least 24 hr before BIS scoring. The BIS value, GCS scores, and Full Outline of UnResponsiveness (FOUR) were monitored hourly for 48 hr. Based on the Glasgow Outcome Scale (GOS) score, the patients were divided into poor (GOS score: 1-2) and good prognosis groups (GOS score: 3-5). The correlation between BIS and prognosis was analyzed by logistic regression, and the receiver operating characteristic curves were plotted. RESULTS: The mean (SD) of the BIS value: 54.63 (11.76), p = .000; and GCS score: 5.76 (1.87), p = .000, were higher in the good prognosis group than in the poor prognosis group. Lower BIS values and GCS scores were correlated with poorer prognosis. Based on the area under the curve of receiver operating characteristic curves, the optimal diagnostic cutoff value of the BIS was 43.6, and the associated sensitivity and specificity were 85.4% and 74.4%, respectively. CONCLUSION: Taken together, our study indicates that BIS had good predictive value on prognosis. These findings suggested that BIS could be used to evaluate the severity and prognosis of severe brain injury.

Increased Levels of Pro-Inflammatory and Anti-Inflammatory Cellular Responses in Parkinson's Disease Patients: Search for a Disease Indicator.

BACKGROUND Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder and it arises when most of the dopaminergic neurons of substantia nigra region die. Several mechanisms have been postulated as the causative event in PD pathology, and neuroinflammation is most crucial among them. MATERIAL AND METHODS We analyzed T-helper 17 (Th17) cells and myeloid-derived suppressor cells (MDSCs) from 80 PD patients to assess inflammatory processes and to find a cost-effective means to evaluate PD prognosis. RESULTS We found significantly increased numbers of Th17 cells and MDSCs count in peripheral circulation in PD patients compared with controls (p<0.001). A positive correlation was found between Th17 cells and MDSCs in PD patients (r=0.421, p<0.05). CONCLUSIONS Our results show the effector role of Th17 cells and MDSCs in PD pathology and shows their utility as effective biomarkers for PD diagnosis.