Transplantation of the Mammalian Pineal Gland: Studies of Survival, Revascularization, Reinnervation and Recovery of Function

The survival, revascularization, reinnervation, and recovery of function of transplanted newborn rat pineal glands were studied following grafting into four different locations in pinealectomized rats. These locations were the third cerebral ventricle, in situ (where the pineal gland is normally located), the renal capsule, and the anterior chamber of the eye. Pinealocytes in the grafts maintained high metabolic activity as evidenced by the presence of euchromatic nuclei, prominent nucleoli, infolded nuclear envelopes, numerous mitochondria and Golgi apparati, and relatively abundant endoplasmic reticulum and ribosomes. In addition, morphological correlates of two putative secretory processes were observed in the grafts. The first type was neurosecretory-like (Golgi apparatus--dense-core vesicles) and the second was ependymal-like (rough endoplasmic reticulum--vacuoles containing flocculent material). Pineal grafts were well vascularized by fenestrated capillaries surrounded by consistently wide perivascular spaces. Moreover, nerve fibers and terminals were seen in the grafts within the anterior chamber of the eye, the third cerebral ventricle, and the pineal region (in situ transplantation). By contrast, no fibers or terminals were found in grafts placed beneath the renal capsule. Reinnervating neurites in the grafts within the anterior eye chamber were found throughout the graft while those in the ventricular grafts and the in situ grafts were more abundant in some regions than in others. Nighttime serum melatonin levels increased significantly in pinealectomized rats with transplants into either the third cerebral ventricle or the anterior eye chamber. This increase might reflect graft reinnervation. Yet day-night differences in serum melatonin were observed only in host rats receiving transplants to the anterior eye chamber. These differences were eliminated by bilateral removal of the superior cervical ganglion. In conclusion, pinealocytes survived transplantation and exhibited ultrastructural features indicative of active secretory processes. Moreover, pineal grafts were well vascularized by fenestrated capillaries. Synthesis and release of melatonin is restored following transplantation into the third cerebral ventricle or the anterior chamber of the eye. However, day-night differences in serum melatonin is only restored following transplants into the anterior eye chamber. Finally, reinnervation of the grafts by the host superior cervical ganglion is necessary for this restoration

Histological analysis of motoneuron survival and microglia inhibition after nerve root avulsion treated with nerve graft implantation and minocycline: an experimental study

Motor vehicle accidents are the most common cause of injuries involving avulsion of the brachial plexus in humans, resulting in debilitating motor dysfunction. Lack of an established animal model to test drug treatments hinders the introduction of new pharmacological agents. Avulsion injury of cervical ventral roots can be replicated in rats, resulting in a progressive loss of the motoneurons and increase in neurotoxic expression of microglia. This is a report on the effect of prompt nerve implantation and minocycline treatment on the suppression of microglia activation and survival of motoneurons. 20 adult female Sprague-Dawley rats were used for this study, which was approved by the Animal Ethical Committee, USM (approval number /2011/(73)(346)). The animals underwent surgical avulsion of the C6 nerve root, followed by reimplantation with peripheral nerve graft and treatment with intraperitoneal minocycline. At 6 weeks postoperatively, immunohistochemistry using primary antibody Iba1 (microglia) and nicotinamide adenine dinucleotide phosphate diaphorase (NADPh) with neutral-red staining (motoneuron) under flourescence microscopy was performed at the C6 spinal cord segment and then quantified. This study showed signifi cant reduction of microglia expression in the study group; mean ranks of control and study group were 15.2 and 11.6, respectively; U=9.5, Z=3.02, p0.05. This may be due to the effect of the surgery; the surgery has the potential to cause additional trauma to the cord parenchyma, leading to further motoneuron loss and an increase in scarring around the avulsed region, thus impeding regeneration of the motoneuron

Use of Self-Assembly Nanofibre Biomaterials for Neural Repair After Injury

published_or_final_versio

What Does Economics Assume About People’s Knowledge? Who knows?

The purpose of the paper is to explore, from an assessment viewpoint, the ideas below. Economics, as a social science, has always considered sets of individuals with assumed characteristics, namely the level of knowledge, although in an implicit way in most of the cases. In this sense, an influential approach in Economics assumed that society, as a global set of individuals, was characterised by a certain level of knowledge that, indeed, could be associated with the one of its representative agent. In fact, an attentive recall of the evolution of these matters in Economics will immediately recognise that, since the very first economic models of the government, it was assumed that the level of knowledge of society, represented by a set of voters, was not the same as the one of the agent being elected, i.e. the government. The irrelevance of the difference in the level of knowledge of economic agents was soon abandoned after some seminal works of Hayek and Friedman. More recently, the viewpoint of Economics has changed by focusing on the characteristics (e.g. knowledge) of individuals, who may interact in sub-sets of society. From this point of view is clearly relevant, given the close connection with the assumed level of knowledge, to distinguish the adaptive behaviour from the rational one, as well as the full rational from the bounded rationality behaviour by people. Quite recent developments in the Economics of Knowledge, i.e. the so-called learning models, have been considered as more realistic approaches to model the process by which individuals acquire knowledge, for instance from other individuals that are, themselves, acquiring knowledge

Next generation histology methods for three-dimensional imaging of fresh and archival human brain tissues

Current available tissue clearing techniques are mostly used for rodent tissues. Here, the authors develop OPTIClear solution for fresh and archival human brain tissue clearing and establish associated protocols for three-dimensional histological investigations

Rationalisation and Validation of an Acrylamide-Free Procedure in Three-Dimensional Histological Imaging

201810_a bcmapublished_fina

Surgical intervention combined with weight-bearing walking training improves neurological recoveries in 320 patients with clinically complete spinal cord injury: a prospective self-controlled study

Although a large number of trials in the SCI field have been conducted, few proven gains have been realized for patients. In the present study, we determined the efficacy of a novel combination treatment involving surgical intervention and long-term weight-bearing walking training in spinal cord injury (SCI) subjects clinically diagnosed as complete or American Spinal Injury Association Impairment Scale (AIS) Class A (AIS-A). A total of 320 clinically complete SCI subjects (271 male and 49 female), aged 16-60 years, received early (≤ 7 days, n = 201) or delayed (8-30 days, n = 119) surgical interventions to reduce intraspinal or intramedullary pressure. Fifteen days post-surgery, all subjects received a weight-bearing walking training with the "Kunming Locomotion Training Program (KLTP)" for a duration of 6 months. The neurological deficit and recovery were assessed using the AIS scale and a 10-point Kunming Locomotor Scale (KLS). We found that surgical intervention significantly improved AIS scores measured at 15 days post-surgery as compared to the pre-surgery baseline scores. Significant improvement of AIS scores was detected at 3 and 6 months and the KLS further showed significant improvements between all pair-wise comparisons of time points of 15 days, 3 or 6 months indicating continued improvement in walking scores during the 6-month period. In conclusion, combining surgical intervention within 1 month post-injury and weight-bearing locomotor training promoted continued and statistically significant neurological recoveries in subjects with clinically complete SCI, which generally shows little clinical recovery within the first year after injury and most are permanently disabled. This study was approved by the Science and Research Committee of Kunming General Hospital of PLA and Kunming Tongren Hospital, China and registered at ClinicalTrials.gov (Identifier: NCT04034108) on July 26, 2019

Soluble NgR Fusion Protein Modulates the Proliferation of Neural Progenitor Cells via the Notch Pathway

NogoA, myelin-associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein are CNS myelin molecules that bind to the neuronal Nogo-66 receptor (NgR) and inhibit axon growth. The NgR antagonist, soluble NgR1-Fc protein (sNgR-Fc), facilitates axon regeneration by neutralizing the inhibitory effects of myelin proteins in experimental models of CNS injury. Here we aim to investigate the effect of sNgR-Fc on the proliferation of neural progenitor cells (NPCs). The hippocampus cells of embryonic rats were isolated and cultured in vitro. The expression of nestin, βIII-Tubulin, GFAP and Nogo-A on these cells was observed using immunocytochemistry. In order to investigate the effect on proliferation of NPCs, sNgR-Fc, MAG-Fc chimera and Notch1 blocker were added respectively. The total cell number for the proliferated NPCs was counted. BrdU was applied and the rate of proliferating cells was examined. The level of Notch1 was analyzed using Western blotting. We identified that NogoA is expressed in NPCs. sNgR-Fc significantly enhanced the proliferation of NPCs in vitro as indicated by BrdU labeling and total cell count. This proliferation effect was abolished by the administration of MAG suggesting specificity. In addition, we demonstrate that sNgR-Fc is a potent activator for Notch1 and Notch1 antagonist reversed the effect of sNgR-Fc on NPC proliferation. Our results suggest that sNgR-Fc may modulate Nogo activity to induce NPC proliferation via the Notch pathway

Generation of integration-free neural progenitor cells from cells in human urine

Human neural stem cells hold great promise for research and therapy in neural disease. We describe the generation of integration-free and expandable human neural progenitor cells (NPCs). We combined an episomal system to deliver reprogramming factors with a chemically defined culture medium to reprogram epithelial-like cells from human urine into NPCs (hUiNPCs). These transgene-free hUiNPCs can self-renew and can differentiate into multiple functional neuronal subtypes and glial cells in vitro. Although functional in vivo analysis is still needed, we report that the cells survive and differentiate upon transplant into newborn rat brain.postprin