Transplants of encapsulated rat choroid plexus cells exert neuroprotection in a rodent model of Huntington's disease

Choroid plexus (CP) epithelial cells secrete several neurotrophic factors and have been used in transplantation studies designed to impart neuroprotection against central nervous system (CNS) trauma. In the present study, CP was isolated from adult rats, encapsulated within alginate microcapsules, and transplanted unilaterally into the rat striatum. Three days later, unilateral injections of quinolinic acid (QA; 225 nmol) were made into the ipsilateral striatum to mimic the pathology observed in Huntington's disease (HD). After surgery, animals were tested for motor function using the placement test. Rats receiving CP transplants were significantly less impaired on this test. Nissl-stained sections demonstrated that CP transplants significantly reduced the volume of the striatal lesion produced by QA. Quantitative analysis of striatal neurons further demonstrated that choline acetyltransferase-immunoreactive, but not diaphorase-positive, neurons were protected by CP transplants. These data demonstrate that transplanted CP cells can be used to protect striatal neurons from excitotoxic damage and that the pattern of neuroprotection varies across specific neuronal populations.     

Deregulated overexpression of hCdt1 and hCdc6 promotes malignant behavior

The accurate execution of DNA replication requires a strict control of the replication licensing factors hCdt1 and hCdc6. The role of these key replication molecules in carcinogenesis has not been clarified. To examine how early during cancer development deregulation of these factors occurs, we investigated their status in epithelial lesions covering progressive stages of hyperplasia, dysplasia, and full malignancy, mostly from the same patients. Abnormal accumulation of both proteins occurred early from the stage of dysplasia. A frequent cause of unregulated hCdc6 and hCdt1 expression was gene amplification, suggesting that these components can play a role per se in cancer development. Overexpression of hCdt1 and hCdc6 promoted rereplication and generated a DNA damage response, which activated the antitumor barriers of senescence and apoptosis. Generating an inducible hCdt1 cellular system, we observed that continuous stimulus by deregulated hCdt1 led to abrogation of the antitumor barriers and resulted in the selection of clones with more aggressive properties. In addition, stable expression of hCdc6 and hCdt1 in premalignant papilloma cells led to transformation of the cells that produced tumors upon injection into nude mice depicting the oncogenic potential of their deregulation.     

Glucocorticoid effects on axonal regeneration of retinal ganglion cells in vitro

Although glucocorticoids are commonly used for the treatment of optic nerve inflammations, little is known about direct effects of steroids on retinal nerve cells. In this study, the neuritogenic effect of prednisolone on retinal ganglion cells was investigated using retinal organ cultures derived from adult rats and embryonic chickens. The numbers of axons growing from retinal ganglion cells (RGC) in vitro were counted to measure the regenerative propensity at various corticosteroid concentrations. Prednisolone exerted a dose-dependent neuritogenic influence on RGC of either origin. The effect was highest at a concentration of 25 μg/ml culture medium, where axon numbers increased to 237% (rat) and 166% (chick) of the control values. This was highly significant (t-test: P < 0.01 and P < 0.005, respectively). High corticosteroid concentrations (>125 μg/ml) produced toxic effects, as revealed by low axon numbers as well as morphological alterations of the explants.     

Commentary: The need for research on PTSD in Children and adolescents – a commentary on Elliot et al. (2020)

The recent release of the 11th version of The International Classification of Diseases (ICD-11: WHO, 2018) marked a significant departure from the previous similarities between it and the Diagnostic and Statistical Manual of Mental Disorders (DSM-5; APA, 2013) in terms of their conceptualization of posttraumatic stress disorder (PTSD). The ICD-11 proposed a reduced symptom set for PTSD and a sibling disorder called Complex PTSD. There have been numerous studies that have provided support for the integrity of, and distinction between, PTSD and CPTSD diagnoses in adult samples. Elliot and colleagues (2020) have added to the research literature by providing a valuable examination of the differences between ICD and DSM PTSD/CPTSD in a sample of youth aged 8 to 17 years. This commentary reviews this study and reflects on the need for greater understanding of developmental changes in the presentation of PTSD and Complex PTSD.     

Insulin-like growth factor-I promotes nerve regeneration through a nerve graft in an experimental model of facial paralysis

Among the pathological sequelae of facial paralysis is a paralytic eye. Apart from the psychological and aesthetic deficits, facial paralysis if left untreated can lead to dryness, ulceration and eventual blindness. Although numerous restorative microsurgical approaches have been introduced to address the sequelae of this problem, complete restoration of function to denervated facial muscles remains elusive.Utilizing the rat model of facial paralysis the present research has as an objective to examine a dual treatment approach. Specifically, this study combined the current microsurgical treatment of the cross-facial nerve graft with local administration of insulin-like growth factor I (IGF-I).The efficacy of this combined approach (cross-facial nerve graft + IGF-I) was assessed in the following ways: (a) behavior measurement of the blink response and (b) histomorphometry light and electron microscopy of the entire nerve graft. These data will help provide insight into the restoration of facial muscle function after trauma and assist in the future development of more potent treatment strategies.7he local adnünistration of IGF-I (50 micro g/ml) to the cross-facial nerve graft was found to restore the blink response faster and to strengthen the degree of eye closure. Light microscopy examination revealed that IGF-I significantly enhanced axonal regeneration within a nerve graft (a 22% increase in the mean number of axons), and increased the mean nerve fiber diameter and myelin thickness. Electron microscopy assessment of the nerve grafts demonstrated that the IGF-I treated grafts possessed a greater density of microtubules, which were evenly distributed within the axoplasm.     

Skeletonization of radial and gastroepiploic conduits in coronary artery bypass surgery

The use of a skeletonized internal thoracic artery in coronary artery bypass graft surgery has been shown to confer certain advantages over a traditional pedicled technique, particularly in certain patient groups. Recent reports indicate that radial and gastroepiploic arteries can also be harvested using a skeletonized technique. The aim of this study is to systematically review the available evidence regarding the use of skeletonized radial and gastroepiploic arteries within coronary artery bypass surgery, focusing specifically on it's effect on conduit length and flow, levels of endothelial damage, graft patency and clinical outcome. Four electronic databases were systematically searched for studies reporting the utilisation of the skeletonization technique within coronary revascularisation surgery in humans. Reference lists of all identified studies were checked for any missing publications. There appears to be some evidence that skeletonization may improve angiographic patency, when compared with pedicled vessels in the short to mid-term. We have found no suggestion of increased complication rates or increased operating time. Skeletonization may increase the length of the conduit, and the number of sequential graft sites, but no clear clinical benefits are apparent. Our study suggests that there is not enough high quality or consistent evidence to currently advocate the application of this technique to radial or gastroepiploic conduits ahead of a traditional pedicled technique.     

Receptor interacting protein kinases mediate retinal detachment-induced photoreceptor necrosis and compensate for inhibition of apoptosis

Apoptosis has been shown to be a significant form of cell loss in many diseases. Detachment of photoreceptors from the retinal pigment epithelium, as seen in various retinal disorders, causes photoreceptor loss and subsequent vision decline. Although caspase-dependent apoptotic pathways are activated after retinal detachment, caspase inhibition by the pan-caspase inhibitor Z-VAD fails to prevent photoreceptor death; thus, we investigated other pathways leading to cell loss. Here, we show that receptor interacting protein (RIP) kinase-mediated necrosis is a significant mode of photoreceptor cell loss in an experimental model of retinal detachment and when caspases are inhibited, RIP-mediated necrosis becomes the predominant form of death. RIP3 expression, a key activator of RIP1 kinase, increased more than 10-fold after retinal detachment. Morphological assessment of detached retinas treated with Z-VAD showed decreased apoptosis but significantly increased necrotic photoreceptor death. RIP1 kinase inhibitor necrostatin-1 or Rip3 deficiency substantially prevented those necrotic changes and reduced oxidative stress and mitochondrial release of apoptosis-inducing factor. Thus, RIP kinase-mediated programmed necrosis is a redundant mechanism of photoreceptor death in addition to apoptosis, and simultaneous inhibition of RIP kinases and caspases is essential for effective neuroprotection and may be a novel therapeutic strategy for treatment of retinal disorders.