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Biology Apr 2023Ischemic stroke is one of the leading causes of death worldwide, and poses a great burden to society and the healthcare system. There have been many recent advances in... (Review)
Review
Ischemic stroke is one of the leading causes of death worldwide, and poses a great burden to society and the healthcare system. There have been many recent advances in the treatment of ischemic stroke, which usually results from the interruption of blood flow to a particular part of the brain. Current treatments for ischemic stroke mainly focus on revascularization or reperfusion of cerebral blood flow to the infarcted tissue. Nevertheless, reperfusion injury may exacerbate ischemic injury in patients with stroke. In recent decades, vagus nerve stimulation (VNS) has emerged as an optimistic therapeutic intervention. Accumulating evidence has demonstrated that VNS is a promising treatment for ischemic stroke in various rat models through improved neural function, cognition, and neuronal deficit scores. We thoroughly examined previous evidence from stroke-induced animal studies using VNS as an intervention until June 2022. We concluded that VNS yields stroke treatment potential by improving neurological deficit score, infarct volume, forelimb strength, inflammation, apoptosis, and angiogenesis. This review also discusses potential molecular mechanisms underlying VNS-mediated neuroprotection. This review could help researchers conduct additional translational research on patients with stroke.
PubMed: 37106754
DOI: 10.3390/biology12040555 -
Neural Regeneration Research Mar 2020Peripheral nerve repair is required after traumatic injury. This common condition represents a major public health problem worldwide. Recovery after nerve repair depends...
OBJECTIVE
Peripheral nerve repair is required after traumatic injury. This common condition represents a major public health problem worldwide. Recovery after nerve repair depends on several factors, including the severity of the injury, the nerve involved, and the surgeon's technical skills. Despite the precise microsurgical repair of nerve lesions, adequate functional recovery is not always achieved and, therefore, the regeneration process and surgical techniques are still being studied. Pre-clinical animal models are essential for this research and, for this reason, the focus of the present systematic review (according to the PRISMA statement) was to analyze the different animal models used in pre-clinical peripheral nerve repair studies.
DATA SOURCES
Original articles, published in English from 2000 to 2018, were collected using the Web of Science, Scopus, and PubMed databases.
DATA SELECTION
Only preclinical trials on direct nerve repair were included in this review. The articles were evaluated by the first two authors, in accordance with predefined data fields.
OUTCOME MEASURES
The primary outcomes included functional motor abilities, daily activity and regeneration rate. Secondary outcomes included coaptation technique and animal model.
RESULTS
This review yielded 267 articles, of which, after completion of the screening, 49 studies were analyzed. There were 1425 animals in those 49 studies, being rats, mice, guinea pigs, rabbits, cats and dogs the different pre-clinical models. The nerves used were classified into three groups: head and neck (11), forelimb (8) and hindlimb (30). The techniques used to perform the coaptation were: microsuture (46), glue (12), laser (8) and mechanical (2). The follow-up examinations were histology (43), electrophysiological analysis (24) and behavioral observation (22).
CONCLUSION
The most widely used animal model in the study of peripheral nerve repair is the rat. Other animal models are also used but the cost-benefit of the rat model provides several strengths over the others. Suture techniques are currently the first option for nerve repair, but the use of glues, lasers and bioengineering materials is increasing. Hence, further research in this field is required to improve clinical practice.
PubMed: 31571661
DOI: 10.4103/1673-5374.266068 -
Frontiers in Cellular Neuroscience 2020Neural stimulation modulates the depolarization of neurons, thereby triggering activity-associated mechanisms of neuronal plasticity. Activity-associated mechanisms in...
Neural stimulation modulates the depolarization of neurons, thereby triggering activity-associated mechanisms of neuronal plasticity. Activity-associated mechanisms in turn play a major role in post-mitotic structure and function of adult neurons. Our understanding of the interactions between neuronal behavior, patterns of neural activity, and the surrounding environment is evolving at a rapid pace. Brain derived neurotrophic factor is a critical mediator of activity-associated plasticity, while multiple immediate early genes mediate plasticity of neurons following bouts of neural activity. New research has uncovered genetic mechanisms that govern the expression of DNA following changes in neural activity patterns, including RNAPII pause-release and activity-associated double stranded breaks. Discovery of novel mechanisms governing activity-associated plasticity of neurons hints at a layered and complex molecular control of neuronal response to depolarization. Importantly, patterns of depolarization in neurons are shown to be important mediators of genetic expression patterns and molecular responses. More research is needed to fully uncover the molecular response of different types of neurons-to-activity patterns; however, known responses might be leveraged to facilitate recovery after neural damage. Physical rehabilitation through passive or active exercise modulates neurotrophic factor expression in the brain and spinal cord and can initiate cortical plasticity commensurate with functional recovery. Rehabilitation likely relies on activity-associated mechanisms; however, it may be limited in its application. Electrical and magnetic stimulation direct specific activity patterns not accessible through passive or active exercise and work synergistically to improve standing, walking, and forelimb use after injury. Here, we review emerging concepts in the molecular mechanisms of activity-derived plasticity in order to highlight opportunities that could add value to therapeutic protocols for promoting recovery of function after trauma, disease, or age-related functional decline.
PubMed: 33173465
DOI: 10.3389/fncel.2020.00271 -
Stem Cells Translational Medicine Dec 2021Perinatal brain injury can lead to significant neurological and cognitive deficits and currently no therapies can regenerate the damaged brain. Neural stem cells (NSCs)... (Meta-Analysis)
Meta-Analysis
Perinatal brain injury can lead to significant neurological and cognitive deficits and currently no therapies can regenerate the damaged brain. Neural stem cells (NSCs) have the potential to engraft and regenerate damaged brain tissue. The aim of this systematic review was to evaluate the preclinical literature to determine whether NSC administration is more effective than controls in decreasing perinatal brain injury. Controlled interventional studies of NSC therapy using animal models of perinatal brain injury were identified using MEDLINE and Embase. Primary outcomes were brain infarct size, motor, and cognitive function. Data for meta-analysis were synthesized and expressed as standardized mean difference (SMD) with 95% confidence intervals (CI), using a random effects model. We also reported secondary outcomes including NSC survival, migration, differentiation, and effect on neuroinflammation. Eighteen studies met inclusion criteria. NSC administration decreased infarct size (SMD 1.09; CI: 0.44, 1.74, P = .001; I = 74%) improved motor function measured via the impaired forelimb preference test (SMD 2.27; CI: 0.85, 3.69, P = .002; I = 86%) and the rotarod test (SMD 1.88; CI: 0.09, 3.67, P = .04; I = 95%). Additionally, NSCs improved cognitive function measured via the Morris water maze test (SMD of 2.41; CI: 1.16, 3.66, P = .0002; I = 81%). Preclinical evidence suggests that NSC therapy is promising for the treatment of perinatal brain injury. We have identified key knowledge gaps, including the lack of large animal studies and uncertainty regarding the necessity of immunosuppression for NSC transplantation in neonates. These knowledge gaps should be addressed before NSC treatment can effectively progress to clinical trial.
Topics: Animals; Brain Injuries; Cell Differentiation; Cognition; Neural Stem Cells; Stem Cell Transplantation
PubMed: 34542242
DOI: 10.1002/sctm.21-0243