https://journals.sagepub.com/doi/pdf/10.1177/0963689717714102

Traumatic Brain Injury: Current Treatment Strategies and Future Endeavors

Traumatic brain injury (TBI) is one of the leading causes of death of young people in the developed world. In the United States alone, 1.7 million traumatic events occur annually accounting for 50,000 deaths. The etiology of TBI includes traffic accidents, falls, gunshot wounds, sports, and combat-related events. TBI severity ranges from mild to severe. TBI can induce subtle changes in molecular signaling, alterations in cellular structure and function, and/or primary tissue injury, such as contusion, hemorrhage, and diffuse axonal injury. TBI results in blood-brain barrier (BBB) damage and leakage, which allows for increased extravasation of immune cells (i.e., increased neuroinflammation). BBB dysfunction and impaired homeostasis contribute to secondary injury that occurs from hours to days to months after the initial trauma. This delayed nature of the secondary injury suggests a potential therapeutic window. The focus of this article is on the (1) pathophysiology of TBI and (2) potential therapies that include biologics (stem cells, gene therapy, peptides), pharmacological (anti-inflammatory, antiepileptic, progrowth), and noninvasive (exercise, transcranial magnetic stimulation). In final, the review briefly discusses membrane/lipid rafts (MLR) and the MLR-associated protein caveolin (Cav). Interventions that increase Cav-1, MLR formation, and MLR recruitment of growth-promoting signaling components may augment the efficacy of pharmacologic agents or already existing endogenous neurotransmitters and neurotrophins that converge upon progrowth signaling cascades resulting in improved neuronal function after injury.

Pathophysiology Associated with Traumatic Brain Injury: Current Treatments and Potential Novel Therapeutics.

Traumatic brain injury (TBI) remains a major cause of death and disability worldwide. Increasing evidence indicates that TBI is an important risk factor for neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and chronic traumatic encephalopathy. Despite improved supportive and rehabilitative care of TBI patients, unfortunately, all late phase clinical trials in TBI have yet to yield a safe and effective neuroprotective treatment. The disappointing clinical trials may be attributed to variability in treatment approaches and heterogeneity of the population of TBI patients as well as a race against time to prevent or reduce inexorable cell death. TBI is not just an acute event but a chronic disease. Among many mechanisms involved in secondary injury after TBI, emerging preclinical studies indicate that posttraumatic prolonged and progressive neuroinflammation is associated with neurodegeneration which may be treatable long after the initiating brain injury. This review provides an overview of recent understanding of neuroinflammation in TBI and preclinical cell-based therapies that target neuroinflammation and promote functional recovery after TBI.

Current understanding of neuroinflammation after traumatic brain injury and cell-based therapeutic opportunities.

Anemia is frequent among brain-injured patients, where it has been associated with an increased risk of poor outcome. The pathophysiology of anemia in this patient population remains multifactorial; moreover, whether anemia merely reflects a higher severity of the underlying disease or is a significant determinant of the neurological recovery of such patients remains unclear. Interestingly, the effects of red blood cell transfusions (RBCT) in moderately anemic patients remain controversial; although hemoglobin levels are increased, different studies observed only a modest and inconsistent improvement in cerebral oxygenation after RBCT and raised serious concerns about the risk of increased complications. Thus, considering this "blood transfusion anemia paradox", the optimal hemoglobin level to trigger RBCT in brain-injured patients has not been defined yet; also, there is insufficient evidence to provide strong recommendations regarding which hemoglobin level to target and which associated transfusion strategy (restrictive versus liberal) to select in this patient population. We summarize in this review article the more relevant studies evaluating the effects of anemia and RBCT in patients with an acute neurological condition; also, we propose some potential strategies to optimize transfusion management in such patients.

/pdf/anemia-management-after-acute-brain-injury-14vfn5o1j0.pdf

Anemia management after acute brain injury

Traumatic brain injury (TBI) is immediate damage caused by a blow to the head resulting from traffic accidents, falls, and sporting activity, which causes death or serious disabilities in survivors. TBI induces multiple secondary injuries, including neuroinflammation, disruption of the blood-brain barrier (BBB), and brain edema. Despite these emergent conditions, current therapies for TBI are limited or insufficient in some cases. Although several candidate drugs exerted beneficial effects in TBI animal models, most of them failed to show significant effects in clinical trials. Multiple studies have suggested that astrocytes play a key role in the pathogenesis of TBI. Increased reactive astrocytes and astrocyte-derived factors are commonly observed in both TBI patients and experimental animal models. Astrocytes have beneficial and detrimental effects on TBI, including promotion and restriction of neurogenesis and synaptogenesis, acceleration and suppression of neuroinflammation, and disruption and repair of the BBB via multiple bioactive factors. Additionally, astrocytic aquaporin-4 is involved in the formation of cytotoxic edema. Thus, astrocytes are attractive targets for novel therapeutic drugs for TBI, although astrocyte-targeting drugs have not yet been developed. This article reviews recent observations of the roles of astrocytes and expected astrocyte-targeting drugs in TBI.

https://www.mdpi.com/1422-0067/22/12/6418/pdf

Pathophysiological Responses and Roles of Astrocytes in Traumatic Brain Injury.

Emerging evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may exert positive effects in patients with depression. Our aim was to conduct a systematic review and meta-analysis to examine the antidepressant effects of GLP-1RAs.Randomized controlled trials and prospective cohort studies investigating the effects of GLP-1RAs versus placebo or other antidiabetic therapies on depressive symptoms were searched for using multiple electronic sources (CENTRAL, PubMed, EMBASE, PsycINFO, World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, China Network Knowledge Infrastructure, China Biomedical Database, Wan Fang data, and Chinese Scientific Journals Database) from inception to February 16, 2023. We utilized a random effects model to analyze standardized mean differences for the change in depression rating scales comparing GLP-1RA treated groups with control treated groups.The meta-analysis comprising 2,071 participants included 5 randomized controlled trials and 1 prospective cohort study. The meta-analysis indicated that the change from baseline in depression rating scale scores decreased significantly when patients received treatment with GLP-1RAs compared to control treatments (SMD = -0.12, 95% CI [-0.21, -0.03], pSMD <0.01, I2 = 0%, pQ = 0.52). The subgroup analysis showed that the effects of GLP-1RAs on depressive symptoms were consistent in patients with Type 2 diabetes mellitus (SMD = -0.12, 95% CI [-0.21, -0.03], pSMD <0.01, I2 = 2%, pQ = 0.40).Adults treated with GLP-1RAs showed significant reductions in the depression rating scale scores compared to those treated with control substances. Our findings suggest that GLP-1RAs may be a potential treatment for alleviating depressive symptoms in humans. 

The Antidepressant Effects of GLP-1 Receptor Agonists: A Systematic Review and Meta-Analysis.

Objective This systematic review and meta-analysis aimed to evaluate the effects of SGLT-2 inhibitors (SGLT-2i) on endothelial function and arteriosclerosis in diabetic patients. Methods Randomized controlled trials (RCTs) were retrieved from PubMed, Embase, Cochrane Library, and Web of Science databases to evaluate the effects of SGLT-2i on endothelial function and atherosclerosis in type 2 diabetic patients. Results We selected 9 RCTs and 2 cohort studys involving 868 patients. Of these, six studies provided flow-mediated dilation (FMD) levels before and after the intervention. The pooled analysis showed that SGLT-2i could significantly improve the FMD compared to the control group (SMD: 0.18, 95% CI: 0.02 ~ 0.34, P = 0.03). Three studies provided the change in FMD before and after the intervention. Pooled analysis showed no significant differences in FMD change between the SGLT-2i group and the control group. (MD: 2.1, 95%-CI: -0.11~4.31, P = 0.06). Five studies showed pulse wave velocity (PWV) results. Pooled analysis showed no significant differences in the change in PWV between the SGLT-2i group and the control group (SMD: 0.11, 95%-CI: − 0.15 ~ 0.37, P = 0.4). Conclusions The ability of SGLT-2 inhibitors to improve FMD was significant, but there was no significant effect on PWV levels. SGLT-2i was superior to other antidiabetic agents in improving arterial endothelial function.

/pdf/effects-of-sglt-2-inhibitors-on-vascular-endothelial-1ehr20q5.pdf

Effects of SGLT-2 Inhibitors on Vascular Endothelial Function and Arterial Stiffness in Subjects With Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract Background As a cardiometabolic disease, hypertension has shown an obvious upward trend, becoming a global epidemic chronic disease. Lifestyle intervention is a fundamental method for lowering blood pressure. This systematic review and meta-analysis aimed to evaluate the effects of time-restricted eating (TRE) on blood pressure. Methods Studies were retrieved from the PubMed, Embase, Cochrane Library, and Web of Science databases to evaluate the effects of TRE on blood pressure. The time frame of search was from the start of database construction until July 14, 2022.There were no language restrictions. Meta-analysis and meta-regression were performed using Stata version 16. The weighted mean difference with 95% CI was used to assess the effect of TRE on blood pressure, heart rate, weight, blood glucose, total cholesterol, HDL-C, LDL-C, and triglycerides. The main ending of this article were blood pressure and heart rate, while the secondary ending were weight, blood glucose, total cholesterol, HDL-C, LDL-C, and triglycerides. Results Ten randomized controlled trials involving 694 patients were identified. TRE significantly reduced systolic blood pressure (SBP) (mean difference = −4.15; 95% CI: −6.73, −2.30; P &lt; 0.0001), but had no significant effect on diastolic blood pressure (DBP) (mean difference = −2.06; 95% CI: −4.16, 0.02; P = 0.053) and no beneficial effect on heart rate (mean difference = 0.36; 95% CI: −2.83, 3.54; P = 0.0825). TRE promoted weight loss (mean difference = −1.63; 95% CI: −2.61, −0.64; P = 0.001) and decreased blood glucose levels (mean difference = −2.80; 95% CI: −4.64, −0.96; P = 0.003), but had no significant effect on total cholesterol (mean difference = 0.03, 95% CI: −10.01, 10.08; P = 0.995), HDL-C (mean difference = 0.85, 95% CI: −1.80, 3.49; P = 0.531), LDL-C (mean difference = −0.86, 95% CI: −6.47, 4.76; P = 0.764), or triglycerides (mean difference = −3.524, 95% CI: −9.49, 2.45; P = 0.248). In a separate meta-regression analysis, the degree of SBP change was related to weight loss ( P = 0.044) but not to glucose improvement ( P = 0.867). Conclusions The present meta-analysis suggests that TRE significantly reduced SBP, while no effect of reducing DBP was seen. The observed lower blood pressure may be attributed to significant weight loss. The effects of TRE on heart rate and blood lipid levels were not apparent. 

/pdf/beneficial-effect-of-time-restricted-eating-on-blood-3icdtteh.pdf

Beneficial effect of time-restricted eating on blood pressure: a systematic meta-analysis and meta-regression analysis

Assessment of the impact of shift work on thyroid disorders: a systematic review and meta-analysis

OBJECTIVE
This study aimed to evaluate the effects of Glucagon-like peptide-1 receptor agonist (GLP-1RA) on prediabetes with overweight/obesity.


METHODS
A search of PubMed, Embase, Cochrane Library, and Web of Science databases was performed to identify randomised controlled trials (up to 4 July 2022) which evaluated the effect of GLP-1RA on prediabetes with overweight/obesity.


RESULTS
Eight hundred and nine articles were retrieved (80 from PubMed, 481 from Embase, 137 from Cochrane library, and 111 from Web of Science) and a total of 5 articles were included in this meta-analysis. More individuals in GLP-1RAs group regressed from prediabetes to normoglycemia than individuals in the placebo group (OR = 4.56, 95% CI:3.58, 5.80, P = 0.004); fewer individuals in GLP-1RAs group were diagnosed with diabetes than those in the placebo group (OR = 0.31, 95% CI:0.12,0.81, P = 0.017). Results from five studies showed that GLP-1RAs significantly reduced fasting glucose (mean difference = -0.41 mmol/L, 95% CI: -0.58, -0.25, P < 0.00001), with an acceptable heterogeneity (I2  = 42%).


CONCLUSIONS
The present meta-analysis suggested that GLP-1RA significantly improves glucose metabolism, reduces systolic blood pressure and body weight in prediabetes with overweight/obesity. It could also prevent the development of diabetes and reverse abnormal glucose metabolism.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/dmrr.3680

Effects of treatment with Glucagon-like peptide-1 receptor agonist on prediabetes with overweight/obesity: A systematic review and meta-analysis.

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