Mitigating the impact of mechanisms causing neuronal degeneration

Primary and secondary neurodegeneration is a pathological hallmark of numerous central nervous system(CNS)disorders.Although many mechanisms leading to neurodegeneration are well understood,previous approaches aiming at providing protection from neurodegeneration were often futile.A potential explanation may be that recent research discovered additional pathomechanisms leading to neurodegeneration.Thus,simply targeting single neurodegenerative mechanisms may only have minor therapeutic impact.Addressing multiple neurodegenerative mechanisms may be a more viable strategy.Moreover,the restoration of lost brain tissue turned out to be a very complex endeavor.1 Despite making some initial progress with the use of biocompatible scaffolds and hydrogels.

Activation of neurogenesis in the hippocampus is a novel therapeutic target for Alzheimer's disease

The pathologies associated with age-related brain dysfunction,including Alzheimer's disease(AD),Parkinson's disease,Lewy body dementia,and vascular dementia,often share similarities across multiple diseases.1 While various factors,such as amyloidβ,Tau protein,α-synuclein,chronic inflammation,and impaired cerebral microcirculation have been suggested as potential therapeutic targets,addressing a single factor is unlikely to be sufficient in preventing or treating age-related brain dysfunction.Drawing from these observations.

Exploring novel experimental treatments for major neurodegenerative disorders

Acute and chronic neurodegenerative disorders such as ischemic stroke or Alzheimer's disease(AD)impose a major burden on patients,their relatives,caregivers,and health care systems in general.The socioeconomic impact of neurodegenerative disorders is anticipated to escalate due to a globally ageing population and the increasing prevalence of sedentary lifestyle and inappropriate dietary habits.On the contrary.

Mononuclear cell therapy of neonatal hypoxic-ischemic encephalopathy in preclinical versus clinical studies:A systematic analysis of therapeutic efficacy and study design

Background:Hypoxic-ischemic encephalopathy(HIE)is a devastating condition affecting around 8.5 in 1000 newborns globally.Therapeutic hypothermia(TH)can reduce mortality and,to a limited extent,disability after HIE.Nevertheless,there is a need for new and effective treatment strategies.Cell-based treatments using mononuclear cells(MNCs),which can be sourced from umbilical cord blood,are currently being investigated.Despite promising preclinical results,there is currently no strong indicator for the clinical efficacy of the approach.This analysis aimed to provide potential explanations for this discrepancy.Methods:A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines.Preclinical and clinical studies were retrieved from PubMed,Web of Science,Scopus,and clinicaltrials.gov using a predefined search strategy.A total of 17 preclinical and 7 clinical studies were included.We analyzed overall MNC efficacy in preclinical trials,the methodological quality of preclinical trials,and relevant design features in preclinical versus clinical trials.Results:There was evidence for MNC therapeutic efficacy in preclinical models of HIE.The methodological quality of preclinical studies was not optimal,and statistical design quality was particularly poor.However,methodological quality was above the standard in other fields.There were significant differences in preclinical versus clinical study design including the use of TH as a baseline treatment(only in clinical studies)and much higher MNC doses being applied in preclinical studies.Conclusions:Based on the analyzed data,it is unlikely that therapeutic effect size is massively overestimated in preclinical studies.It is more plausible that the many design differences between preclinical and clinical trials are responsible for the so far lacking proof of the efficacy of MNC treatments in HIE.Additional preclinical and clinical research is required to optimize the application of MNC for experimental HIE treatment.

Join us on an amazing journey towards next-generation treatments for CNS disorders:Launch of Neuroprotection,a new high-quality journal in translational neuroscience

Translational medicine in neurodegenerative and neurovascular diseases is approaching a breakthrough point.Recent years have led to dramatic progress in both experimental and clinical research.Based on a much better and continuously increasing understanding of disease mechanisms,progression and pathophysiology,new therapies with an improved translational potential to protect tissue either against acute or chronic degeneration and even approaches potentially capable of repairing damaged brain tissue are emerging.

Immunosuppression for in vivo research： state-of-the-at protocols and experimental approaches

Almost every experimental treatment strategy using non-autologous cell, tissue or organ transplantation is tested in small and large animal models before clinical translation. Because these strategies require immunosuppression in most cases, immunosuppressive protocols are a key element in transplantation experiments. However, standard immunosuppressive protocols are often applied without detailed knowledge regarding their efficacy within the particular experimental setting and in the chosen model species. Optimization of such protocols is pertinent to the translation of experimental results to human patients and thus warrants further investigation. This review summarizes current knowledge regarding immunosuppressive drug classes as well as their dosages and application regimens with consideration of species-specific drug metabolization and side effects. It also summarizes contemporary knowledge of novel immunomodulatory strategies, such as the use of mesenchymal stem cells or antibodies. Thus, this review is intended to serve as a state-of-the-art compendium for researchers to refine applied experimental immunosuppression and immunomodulation strategies to enhance the predictive value of preclinical transplantation studies.