UNASSIGNED: The findings regarding the prognosis of prolonged disorders of consciousness (PDOC) vary widely among different studies. This study aims to investigate the mortality, consciousness recovery and disabilities of patients with PDOC after brain injury.
UNASSIGNED: A total of 204 patients with PDOC were included in a longitudinal cohort study, including 129 males and 75 females. There were 112 cases of traumatic brain injury (TBI), 62 cases of cerebral hemorrhage (CH), 13 cases of cerebral infarction (CI) and 17 cases of ischemic hypoxic encephalopathy (IHE). The status of consciousness at 1, 2, 3, 6, 12, 18, 24, 36, 48 months of the disease course was assessed or followed up using the Revised Coma Recovery Scale (CRS-R). If the patients were conscious, the disability Rating Scale (DRS) was also performed. The prognosis of different PDOC including coma, vegetative state (VS) and minimal conscious state (MCS) was analyzed. The survival patients were screened for variables and included in multivariate binary Logistic regression to screen the factors affecting the recovery of consciousness.
UNASSIGNED: The mortality rates at 12, 24, 36, and 48 months were 10.7, 23.4, 38.9, and 68.4%, respectively. The median time of death was 18 months (8.75, 29). The probability of MCS regaining consciousness was higher than VS (p < 0.05), with the degree of disability left lower than VS (p < 0.05). There was no significant difference between MCS- and MCS+ groups in terms of the probability of regaining consciousness, the extent of residual disability, and mortality rates (p > 0.05). The mortality rate of coma was higher than that of other PDOC (p < 0.05). The mortality rate of MCS was lower than that of VS, but the difference was not statistically significant (p > 0.05). The probability of consciousness recovery after TBI was the highest and the mortality rate was the lowest. The possibility of consciousness recovery in IHE was the least, and the mortality rate of CI was the highest. The cause of brain injury and initial CRS-R score were the factors affecting the consciousness recovery of patients (p < 0.05).
UNASSIGNED: The prognosis of MCS is more favorable than VS, with comparable outcomes between MCS- and MCS+, while comatose patients was the poorest. TBI has the best prognosis and IHE has the worst prognosis.

Aim: Although lactate supplementation at the reperfusion stage of ischemic stroke has been shown to offer neuroprotection, whether the role of accumulated lactate at the ischemia phase is neuroprotection or not remains largely unknown. Thus, in this study, we aimed to investigate the roles and mechanisms of accumulated brain lactate at the ischemia stage in regulating brain injury of ischemic stroke. Methods and Results: Pharmacological inhibition of lactate production by either inhibiting LDHA or glycolysis markedly attenuated the mouse brain injury of ischemic stroke. In contrast, additional lactate supplement further aggravates brain injury, which may be closely related to the induction of neuronal death and A1 astrocytes. The contributing roles of increased lactate at the ischemic stage may be related to the promotive formation of protein lysine lactylation (Kla), while the post-treatment of lactate at the reperfusion stage did not influence the brain protein Kla levels with neuroprotection. Increased protein Kla levels were found mainly in neurons by the HPLC-MS/MS analysis and immunofluorescent staining. Then, pharmacological inhibition of lactate production or blocking the lactate shuttle to neurons showed markedly decreased protein Kla levels in the ischemic brains. Additionally, Ldha specific knockout in astrocytes (Aldh1l1 CreERT2; Ldha fl/fl mice, cKO) mice with MCAO were constructed and the results showed that the protein Kla level was decreased accompanied by a decrease in the volume of cerebral infarction in cKO mice compared to the control groups. Furthermore, blocking the protein Kla formation by inhibiting the writer p300 with its antagonist A-485 significantly alleviates neuronal death and glial activation of cerebral ischemia with a reduction in the protein Kla level, resulting in extending reperfusion window and improving functional recovery for ischemic stroke. Conclusion: Collectively, increased brain lactate derived from astrocytes aggravates ischemic brain injury by promoting the protein Kla formation, suggesting that inhibiting lactate production or the formation of protein Kla at the ischemia stage presents new therapeutic targets for the treatment of ischemic stroke.

There are over 5.3 million Americans who face acquired brain injury (ABI)-related disability as well as almost 800,000 who suffer from stroke each year. To improve mobility and quality of life, rehabilitation professionals often focus on walking recovery soon after hospital discharge for ABI. Reduced propulsion capacity (force output of the lower limbs to counteract ground reaction forces) negatively impacts walking ability and complicates recovery during rehabilitation for brain injured people. We describe a method, using backward-directed resistance (BDR) in a robotic-based treadmill device, to allow measurement of maximum walking propulsion force (MWPF) that is not otherwise possible during overground walking assessment. Our objective was to test the construct validity of a maximum walking propulsion force (MWPF) measure that reflects a person\'s propulsive strength against applied BDR, while walking on a robotic treadmill-based device for participants with acquired brain injury (ABI). Our study enrolled 14 participants with ABI at an in inpatient rehabilitation in Galveston, TX from 8/1/21 - 4/31/22. The range of weight-adjusted MWPF was 2.6-27.1% body weight (%BW), mean 16.5 ± 8.4%BW, reflecting a wide range of propulsive force capability. The strongest correlation with overground tests was between the 6-minute walk test (6-MWT) distance and the MWPF values (r = 0.83, p < 0.001) with moderate correlations between the 10-meter walk tests at comfortable (CWS) and fast speeds (FWS). The Five Times Sit-to-Stand (used as a standard clinical measure of functional lower extremity strength) and MWPF tests were poorly correlated (r = 0.26, p = 0.4). Forward model selection included 6-MWT distance, age, and overground CWS as significant partial predictors of MWPF. We conclude that this novel MWPF measure is a valid representation of maximum propulsive force effort during walking for people post-ABI. Additional research could help determine the impact of interventions designed to increase propulsive force generation during rehabilitation training to improve overground walking performance.

BACKGROUND: People with acquired brain injury (ABI) may experience concurrent conditions such as, mental health and substance use concerns, that require specialized care. There are services that aim to support people with ABI and these conditions separately; however, little is known about the facilitators and barriers of these services. Therefore, the purpose of this study was to engage stakeholders to investigate the facilitators and barriers of healthcare services for ABI and concurrent issues.
METHODS: Semi-structured focus groups were conducted in-person and virtually with people with ABI, caregivers, healthcare professionals, and policy makers during a one-day event in British Columbia, Canada. Manifest content analysis was used with a constructivist perspective to analyze data.
RESULTS: 90 participants (including 34 people with ABI) provided insights during 15 simultaneous focus groups. Three categories were identified: (1) complexity of ABI, (2) supports, (3) structure of care. Complexity of ABI outlined the ongoing basic needs after ABI and highlighted the need for public awareness of ABI. Supports outlined healthcare professional and community-based supports. Structure of care described people with ABI needing to meet criteria for support, experiences of navigating through the system and necessity of integrated services.
CONCLUSIONS: These findings highlight the facilitators and barriers of healthcare services for ABI and concurrent conditions and provide insights into the changes that may be needed. Doing so can improve the accessibility and quality of ABI healthcare services.

Repositionable self-expanding valves allow for repositioning during deployment to achieve optimal valve placement. However, the risk of brain injury associated with repositioning, as detected by diffusion-weighted magnetic resonance imaging (DW-MRI), is unknown. Consecutive patients undergoing transcatheter aortic valve replacement (TAVR) with repositionable self-expanding valves and receiving DW-MRI before and within 7 days post-TAVR procedure were included. The primary outcomes were incidence, number, total volume, and volume per lesion of the cerebral ischemic lesion in DW-MRI after TAVR. Univariate and multivariate logistic regression assessed the association between repositioning and bigger total lesion volume (> 1 cm3 or > 0.5 cm3). Negative binomial regressions were performed to explore the association between repositioning and number of lesions. A propensity score matching was performed to adjust the potential confounders. Moreover, inverse probability of treatment weighted regression model with nonstabilized weights was used as sensitivity analysis. Among 243 included patients, repositioning was performed in 116 (47.7%) patients. The incidence of overt stroke (1.7% vs. 1.6%, p = 0.927) and silent stroke (86.2% vs. 85.8%, p = 0.932) were comparable between two groups. However, the number of new lesions (5.0 [2.0-9.0] vs. 3.0 [2.0-6.0], p = 0.048), and total lesion volume (275.0 [90.0-947.5] mm3 vs. 180.0 [50.0-440.0] mm3, p = 0.022) were significantly higher in the repositioned group. Moreover, the proportion of patients with lesion size greater than 0.5 cm3 was higher in the repositioned group (37.9% vs. 22.0%, p = 0.007). The similar results were observed after propensity score matching. In both multivariate regression model and sensitivity analysis, the repositioning was the independent predictor of number of lesions and bigger total lesion volume after TAVR. The utilization of the repositioning feature may increase the number and volume of silent brain infarcts in DW-MRI in patients who underwent TAVR. (Transcatheter Aortic Valve Replacement Single Center Registry in Chinese Population [TORCH]; NCT02803294).

暂无摘要。

In this study, we examined how systemic inflammation affects repair of brain injury. To this end, we created a brain-injury model by stereotaxic injection of ATP, a damage-associated molecular pattern component, into the striatum of mice. Systemic inflammation was induced by intraperitoneal injection of lipopolysaccharide (LPS-ip). An analysis of magnetic resonance images showed that LPS-ip reduced the initial brain injury but slowed injury repair. An immunostaining analysis using the neuronal marker, NeuN, showed that LPS-ip delayed removal of dead/dying neurons, despite the fact that LPS-ip enhanced infiltration of monocytes, which serve to phagocytize dead cells/debris. Notably, infiltrating monocytes showed a widely scattered distribution. Bulk RNAseq analyses showed that LPS-ip decreased expression of genes associated with phagocytosis, with PCR and immunostaining of injured brains confirming reduced levels of Cd68 and Clec7a, markers of phagocytic activity, in monocytes. Collectively, these results suggest that systemic inflammation affects properties of blood monocytes as well as brain cells, resulting in delay in clearing damaged cells and activating repair processes.

BACKGROUND: Acute hypobaric hypoxia-induced brain injury has been a challenge in the health management of mountaineers; therefore, new neuroprotective agents are urgently required. Meldonium, a well-known cardioprotective drug, has been reported to have neuroprotective effects. However, the relevant mechanisms have not been elucidated. We hypothesized that meldonium may play a potentially novel role in hypobaric hypoxia cerebral injury.
METHODS: We initially evaluated the neuroprotection efficacy of meldonium against acute hypoxia in mice and primary hippocampal neurons. The potential molecular targets of meldonium were screened using drug-target binding Huprot™ microarray chip and mass spectrometry analyses after which they were validated with surface plasmon resonance (SPR), molecular docking, and pull-down assay. The functional effects of such binding were explored through gene knockdown and overexpression.
RESULTS: The study clearly shows that pretreatment with meldonium rapidly attenuates neuronal pathological damage, cerebral blood flow changes, and mitochondrial damage and its cascade response to oxidative stress injury, thereby improving survival rates in mice brain and primary hippocampal neurons, revealing the remarkable pharmacological efficacy of meldonium in acute high-altitude brain injury. On the one hand, we confirmed that meldonium directly interacts with phosphoglycerate kinase 1 (PGK1) to promote its activity, which improved glycolysis and pyruvate metabolism to promote ATP production. On the other hand, meldonium also ameliorates mitochondrial damage by PGK1 translocating to mitochondria under acute hypoxia to regulate the activity of TNF receptor-associated protein 1 (TRAP1) molecular chaperones.
CONCLUSIONS: These results further explain the mechanism of meldonium as an energy optimizer and provide a strategy for preventing acute hypobaric hypoxia brain injury at high altitudes.

Neonatal hypoxic-ischemic (HI) brain injury is a prominent cause of neurological morbidity, urging the development of novel therapies. Interventions with n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) and mesenchymal stem cells (MSCs) provide neuroprotection and neuroregeneration in neonatal HI animal models. While lysophosphatidylcholine (LPC)-bound n-3 LCPUFAs enhance brain incorporation, their effect on HI brain injury remains unstudied. This study investigates the efficacy of oral LPC-n-3 LCPUFAs from Lysoveta following neonatal HI in mice and explores potential additive effects in combination with MSC therapy. HI was induced in 9-day-old C57BL/6 mice and Lysoveta was orally supplemented for 7 subsequent days, with or without intranasal MSCs at 3 days post-HI. At 21-28 days post-HI, functional outcome was determined using cylinder rearing, novel object recognition, and open field tasks, followed by the assessment of gray (MAP2) and white (MBP) matter injury. Oral Lysoveta diminished gray and white matter injury but did not ameliorate functional deficits following HI. Lysoveta did not further enhance the therapeutic potential of MSC therapy. In vitro, Lysoveta protected SH-SY5Y neurons against oxidative stress. In conclusion, short-term oral administration of Lysoveta LPC-n-3 LCPUFAs provides neuroprotection against neonatal HI by mitigating oxidative stress injury but does not augment the efficacy of MSC therapy.

Ultra-high contrast (UHC) MRI describes forms of MRI in which little or no contrast is seen on conventional MRI images but very high contrast is seen with UHC techniques. One of these techniques uses the divided subtracted inversion recovery (dSIR) sequence, which, in modelling studies, can produce ten times the contrast of conventional inversion recovery (IR) sequences. When used in cases of mild traumatic brain injury (mTBI), the dSIR sequence frequently shows extensive abnormalities in white matter that appears normal when imaged with conventional T2-fluid-attenuated IR (T2-FLAIR) sequences. The changes are bilateral and symmetrical in white matter of the cerebral and cerebellar hemispheres. They partially spare the anterior and posterior central corpus callosum and peripheral white matter of the cerebral hemispheres and are described as the whiteout sign. In addition to mTBI, the whiteout sign has also been seen in methamphetamine use disorder and Grinker\'s myelinopathy (delayed post-hypoxic leukoencephalopathy) in the absence of abnormalities on T2-FLAIR images, and is a central component of post-insult leukoencephalopathy syndromes. This paper describes the concept of ultra-high contrast MRI, the whiteout sign, the theory underlying the use of dSIR sequences and post-insult leukoencephalopathy syndromes.