Experimental neurology
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Experimental neurology · Nov 2020
ReviewThe closed-head impact model of engineered rotational acceleration (CHIMERA) as an application for traumatic brain injury pre-clinical research: A status report.
Closed-head traumatic brain injury (TBI) is a worldwide concern with increasing prevalence and cost to society. Rotational acceleration is a primary mechanism in TBI that results from tissue strains that give rise to diffuse axonal injury. The Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA) was recently introduced as a method for the study of impact acceleration effects in pre-clinical TBI research. ⋯ However, the majority of CHIMERA studies only utilize adult male mice. To further establish this model, more work with female animals and various age groups need to be performed, as well as studies to further establish and standardize methodologies for validation of the models for clinical relevance. Common data elements to standardize the reporting methodology for the CHIMERA literature are suggested.
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Experimental neurology · Mar 2020
ReviewPathogenesis of platinum-induced peripheral neurotoxicity: Insights from preclinical studies.
One of the most relevant dose-limiting adverse effects of platinum drugs is the development of a sensory peripheral neuropathy that highly impairs the patients' quality of life. Nowadays there are no available efficacy strategies for the treatment of platinum-induced peripheral neurotoxicity (PIPN), and the only way to prevent its development and progression is by reducing the dose of the cytostatic drug or even withdrawing the chemotherapy regimen. This clinical issue has been the main focus of hundreds of preclinical research works during recent decades. ⋯ This mechanism of DRG sensory neurons cell death is triggered by the nuclear and mitochondrial DNA platination together with the increase of the oxidative cellular status induced by the depletion of cytoplasmic antioxidant mechanisms. However, since there has been no successful transfer of preclinical results to clinical practise in terms of therapeutic approaches, some mechanisms of PIPN pathogenesis still remain to be elucidated. This review is focused on the pathogenic mechanisms underlying PIPN described up to now, provided by the critical analysis of in vitro and in vivo models.
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Experimental neurology · Feb 2020
ReviewPathogenesis of paclitaxel-induced peripheral neuropathy: A current review of in vitro and in vivo findings using rodent and human model systems.
Paclitaxel (Brand name Taxol) is widely used in the treatment of common cancers like breast, ovarian and lung cancer. Although highly effective in blocking tumor progression, paclitaxel also causes peripheral neuropathy as a side effect in 60-70% of chemotherapy patients. Recent efforts by numerous labs have aimed at defining the underlying mechanisms of paclitaxel-induced peripheral neuropathy (PIPN). ⋯ These diverse changes may be secondary to paclitaxel-induced microtubule transport impairment. Human genetic studies, although still limited, also highlight the involvement of cytoskeletal changes in PIPN. Newly identified molecular targets resulting from these studies could provide the basis for the development of therapies with which to either prevent or reverse paclitaxel-induced peripheral neuropathy in chemotherapy patients.
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Experimental neurology · Jan 2020
ReviewNeural-respiratory inflammasome axis in traumatic brain injury.
Traumatic brain injury (TBI) is a leading cause of morbidity and mortality. Approximately 20-25% of TBI subjects develop Acute Lung Injury (ALI), but the pathomechanisms of TBI-induced ALI remain poorly defined. Currently, mechanical ventilation is the only therapeutic intervention for TBI-induced lung injury. ⋯ Here, we outline the role of the extracellular vesicle (EV)-mediated inflammasome signaling in the etiology of TBI-induced ALI. Furthermore, we evaluate the efficacy of a low molecular weight heparin (Enoxaparin, a blocker of EV uptake) and a monoclonal antibody against apoptosis speck-like staining protein containing a caspase recruitment domain (anti-ASC) as therapeutics for TBI-induced lung injury. We demonstate that activation of an EV-mediated Neural-Respiratory Inflammasome Axis plays an essential role in TBI-induced lung injury and disruption of this axis has therapeutic potential as a treatment strategy.
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Experimental neurology · Oct 2019
ReviewDocosahexaenoic acid decreased neuroinflammation in rat pups after controlled cortical impact.
Traumatic brain injury (TBI) is the leading cause of acquired neurologic disability in children, yet specific therapies to treat TBI are lacking. Therapies that decrease the inflammatory response and enhance a reparative immune action may decrease oxidative damage and improve outcomes after TBI. Docosahexaenoic acid (DHA) modulates the immune response to injury in many organs. ⋯ Little is known about DHA effects on neuroinflammation in the developing brain. Further, it is not known if DHA given after developmental TBI exerts neuroprotective effects. We hypothesized that acute DHA treatment would decrease oxidative stress and improve cognitive outcome, associated with decreased pro-inflammatory activation of microglia, the brain's resident macrophages.