Biomaterials and tissue engineering in traumatic brain injury: novel perspectives on promoting neural regeneration.

Traumatic brain injury is a serious medical condition that can be attributed to falls, motor vehicle accidents, sports injuries and acts of violence, causing a series of neural injuries and neuropsychiatric symptoms. However, limited accessibility to the injury sites, complicated histological and anatomical structure, intricate cellular and extracellular milieu, lack of regenerative capacity in the native cells, vast variety of damage routes, and the insufficient time available for treatment have restricted the widespread application of several therapeutic methods in cases of central nervous system injury. Tissue engineering and regenerative medicine have emerged as innovative approaches in the field of nerve regeneration. By combining biomaterials, stem cells, and growth factors, these approaches have provided a platform for developing effective treatments for neural injuries, which can offer the potential to restore neural function, improve patient outcomes, and reduce the need for drugs and invasive surgical procedures. Biomaterials have shown advantages in promoting neural development, inhibiting glial scar formation, and providing a suitable biomimetic neural microenvironment, which makes their application promising in the field of neural regeneration. For instance, bioactive scaffolds loaded with stem cells can provide a biocompatible and biodegradable milieu. Furthermore, stem cells-derived exosomes combine the advantages of stem cells, avoid the risk of immune rejection, cooperate with biomaterials to enhance their biological functions, and exert stable functions, thereby inducing angiogenesis and neural regeneration in patients with traumatic brain injury and promoting the recovery of brain function. Unfortunately, biomaterials have shown positive effects in the laboratory, but when similar materials are used in clinical studies of human central nervous system regeneration, their efficacy is unsatisfactory. Here, we review the characteristics and properties of various bioactive materials, followed by the introduction of applications based on biochemistry and cell molecules, and discuss the emerging role of biomaterials in promoting neural regeneration. Further, we summarize the adaptive biomaterials infused with exosomes produced from stem cells and stem cells themselves for the treatment of traumatic brain injury. Finally, we present the main limitations of biomaterials for the treatment of traumatic brain injury and offer insights into their future potential.

Insights of Chinese herbal medicine for mitochondrial dysfunction in chronic cerebral hypoperfusion induced cognitive impairment: Existed evidences and potential directions.

Chronic cerebral hypoperfusion (CCH) is one of the main pathophysiological markers of cognitive impairment in central nervous system diseases. Mitochondria are cores of energy generation and information process. Mitochondrial dysfunction is the key upstream factors of CCH induced neurovascular pathology. Increasing studies explored the molecular mechanisms of mitochondrial dysfunction and self-repair for effective targets to improve CCH-related cognitive impairment. The clinical efficacy of Chinese herbal medicine in the treatment of CCH induced cognitive impairment is definite. Existed evidences from pharmacological studies have further proved that, Chinese herbal medicine could improve mitochondrial dysfunction and neurovascular pathology after CCH by preventing calcium overload, reducing oxidative stress damage, enhancing antioxidant capacity, inhibiting mitochondria-related apoptosis pathway, promoting mitochondrial biogenesis and preventing excessive activation of mitophagy. Besides, CCH mediated mitochondrial dysfunction is one of the fundamental causes for neurodegeneration pathology aggravation. Chinese herbal medicine also has great potential therapeutic value in combating neurodegenerative diseases by targeting mitochondrial dysfunction.

[Outcomes in randomized controlled trials of acupuncture for vascular cognitive impairment during recent five years].

The existing problems in the outcomes of randomized controlled trials (RCTs) of acupuncture for vascular cognitive impairment (VCI) during recent five years are analyzed and suggestions are proposed. The RCTs of acupuncture for VCI were selected in PubMed, EMbase, Cochrane Library, Clinical Trials, CNKI database, Wanfang database, VIP database, SinoMed database and Chinese Clinical Trial Registry (ChiCTR) from January 1, 2015 to September 14, 2020. The outcomes were extracted and analyzed. As a result, 21 RCTs were included and the outcomes used were divided into 9 categories: clinical symptom/sign indexes, quality of life indexes, neuroimaging indexes, neuroelectrophysiology indexes, blood biochemical indexes, hemorheology indexes, TCM syndrome score indexes, clinical efficacy indexes, and safety indexes. Among them, the top three of the most used outcomes were clinical symptoms/signs indexes (21, 100.0%), clinical efficacy indexes (14, 66.7%) and quality of life indexes (12, 57.1%). In the RCTs of acupuncture for VCI, attention should be paid to distinguish the primary outcomes and secondary outcomes, adopt objective and standardized efficacy evaluation, and give consideration to report the outcomes of safety, health economic and TCM characteristic indexes.

[Overview of systematic reviews of acupuncture for vascular cognitive impairment].

OBJECTIVE: To overview the methodological quality, report quality and evidence quality of the systematic review (SR) of acupuncture for vascular cognitive impairment ( VCI ). METHODS: The SRs regarding acupuncture for VCI were searched in PubMed, Cochrane Library, EMbase, CNKI, SinoMed, Wanfang and VIP databases. The retrieval period was from the establishment of the database to September 24, 2020. The report quality, methodological quality and evidence quality of the included SRs were evaluated by PRISMA statement, the AMSTAR 2 tool and the GRADE system. RESULTS: A total of 22 SRs were included, including 102 outcome indexes. The methodological quality was generally low, with low scores on items 2, 5, 7, 10, 14, 15 and 16. The report quality was good, with scores ranging from 19 points to 24.5 points. The problems of report quality were mainly reflected in the aspects of structural abstract, program and registration, other analysis and funding sources. The level of outcome indexes of SRs was mostly low or very low, and the main leading factor was limitation, followed by inconsistency and inaccuracy. CONCLUSION: Acupuncture for VCI is supported by low quality evidence of evidence-based medicine, but the methodological quality and evidence body quality of relevant SRs are poor, and the standardization is needed to be improved.

EGb in the Treatment for Patients with VCI: A Systematic Review and Meta-Analysis.

BACKGROUND: Ginkgo biloba extract (EGb) is widely used to treat impairments in memory, cognition, activities of daily living, inflammation, edema, stroke, Alzheimer's dementia, and aging. AIM: We aimed to evaluate the safety and efficacy of EGb in treating vascular cognitive impairment (VCI). METHODS: The systematic review was performed using the latest guidelines. We searched for EGb-related trials up to March 1, 2021, in four Chinese databases, three English databases, and clinical trial registry platforms. Randomized controlled trials (RCTs) were included if the study enrolled participants with VCI. Two reviewers independently extracted the data and critically appraised the study quality. Heterogeneity was quantified with I 2. Both sensitivity and subgroup analyses were used to identify the sources of heterogeneity. Publication bias was assessed with funnel plots. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to rate the evidence quality. Outcomes included assessments using the Activities of Daily Living (ADL), Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Hasegawa Dementia Scale (HDS), Barthel Index (BI), Functional Activity Questionnaire (FAQ), and adverse events. RESULTS: In this study, a total of 2019 patients in 23 RCTs were included. EGb appeared to be more effective than control conditions as assessed by the results of cognitive function evaluation, including MMSE (MDMMSE,EGb vs.blank = 3.04, 95% CI: 0.10-5.98; MDMMSE,EGb vs.drugs for VCI = 2.70, 95% CI: 1.39-4.01; MDMMSE,EGb+drugs for VCI vs.blank = 5.90, 95% CI: 4.21-7.59; and MDMMSE,EGb+drugs for VCI vs.drugs for VCI = 3.14, 95% CI: 2.14-4.15), MoCA (MDMoCA,EGb vs.blank = 5.30, 95% CI: 2.15-8.46; MDMoCA,EGb+drugs for VCI vs.blank = 2.66, 95% CI: 1.82-3.50; and MDMoCA,EGb+drugs for VCI vs.drugs for VCI = 2.56, 95% CI: 1.85-3.27), HDS (MDHDS,EGb vs.blank = 6.50; 95% CI: 4.86-8.14; MDHDS,EGb+drugs for VCI vs.drugs for VCI = 3.60, 95% CI: 2.50-4.70), ADL (MDADL,EGb vs.blank = 7.20, 95% CI: 3.28-11.12; MDADL,EGb+drugs for VCI vs.blank = 10.00, 95% CI: 7.51-12.49; and MDADL,EGb+drugs for VCI vs.drugs for VCI = 9.20, 95% CI: 7.26-11.14), BI (MDBI,EGb+drugs for VCI vs.drugs for VCI = 5.71, 95% CI: 2.99-8.43; MDFAQ,EGb vs.drugs for VCI = -1.43, 95% CI: -2.78 to 0.08), and FAQ (MDFAQ,EGb+drugs for VCI vs.drugs for VCI = -2.17, 95% CI: -4.13 to 0.21). Evidence of certainty ranged from medium certainty to very low certainty. CONCLUSION: This meta-analysis showed that EGb may be an effective and safe treatment in improving MMSE, MOCA, ADL, and BI for VCI patients within three months of diagnosis. However, given the quality of the included RCTs, more preregistered trials are needed that explicitly examine the efficacy of EGb. This systematic review has been registered on PROSPERO, with the registration number CRD42021232967.