15 research outputs found
Neuroactive Steroids in Hypoxic–Ischemic Brain Injury: Overview and Future Directions
Hypoxic–ischemic brain injury is a number one cause of long-term neurologic disability and death worldwide. This public health burden is mainly characterized by a decrease in oxygen concentration and blood flow to the tissues, which lead to an inefficient supply of nutrients to the brain. This condition induces cell death by energy depletion and increases free radical generation and inflammation. Hypoxic–ischemic brain injury may occur in ischemic-stroke and over perinatal asphyxia, being both leading causes of morbidity in adults and children, respectively. Currently, there are no effective pharmaceutical strategies to prevent the triggering of secondary injury cascades, including oxidative stress and metabolic dysfunction. Neuroactive steroids like selective estrogen receptor modulators, SERMs, and selective tissue estrogenic activity regulators, STEARs, exert several neuroprotective effects. These encompass mitochondrial survival, a decrease in reactive oxygen species, and maintenance of cell viability, among others. In this context, these neurosteroids constitute promising molecules, which could modify brain response to injury. Here we show an updated overview of the underlying mechanisms of hypoxic–ischemic brain injury. We also highlight the neuroprotective effects of neurosteroids and their future directions
Implementing precision methods in personalizing psychological therapies:Barriers and possible ways forward
The 13th Southern Hemisphere Conference on the Teaching and Learning of Undergraduate Mathematics and Statistics
Ngā mihi aroha ki ngā tangata katoa and warm greetings to you all. Welcome to Herenga
Delta 2021, the Thirteenth Southern Hemisphere Conference on the Teaching and Learning
of Undergraduate Mathematics and Statistics.
It has been ten years since the Volcanic Delta Conference in Rotorua, and we are excited to
have the Delta community return to Aotearoa New Zealand, if not in person, then by virtual
means. Although the limits imposed by the pandemic mean that most of this year’s 2021
participants are unable to set foot in Tāmaki Makaurau Auckland, this has certainly not
stopped interest in this event. Participants have been invited to draw on the concept of
herenga, in Te Reo Māori usually a mooring place where people from afar come to share
their knowledge and experiences. Although many of the participants are still some distance
away, the submissions that have been sent in will continue to stimulate discussion on
mathematics and statistics undergraduate education in the Delta tradition.
The conference invited papers, abstracts and posters, working within the initial themes of
Values and Variables. The range of submissions is diverse, and will provide participants with
many opportunities to engage, discuss, and network with colleagues across the Delta
community. The publications for this thirteenth Delta Conference include publications in the
International Journal of Mathematical Education in Science and Technology, iJMEST,
(available at https://www.tandfonline.com/journals/tmes20/collections/Herenga-Delta-2021),
the Conference Proceedings, and the Programme (which has created some interesting
challenges around time-zones), by the Local Organizing Committee. Papers in the iJMEST
issue and the Proceedings were peer reviewed by at least two reviewers per paper. Of the
ten submissions to the Proceedings, three were accepted.
We are pleased to now be at the business end of the conference and hope that this event will
carry on the special atmosphere of the many Deltas which have preceded this one. We hope
that you will enjoy this conference, the virtual and social experiences that accompany it, and
take the opportunity to contribute to further enhancing mathematics and statistics
undergraduate education.
Ngā manaakitanga,
Phil Kane (The University of Auckland | Waipapa Taumata Rau) on behalf of the Local
Organising Committ
<em>In Vivo</em> Studies of Protein Misfolding and Neurodegeneration Induced by Metabolic Syndrome Relative to Chronic Cerebral Hypoperfusion: A Critical Review
Metabolic syndrome (MetS) leads to microvascular dysfunction and chronic cerebral hypoperfusion (CCH) in an insidious way. Clinical evidence and several rodent models have contributed to determining the neurodegenerative effect of a sustained decrease in cerebral blood flow (CBF). Protein misfolding and aggregation derived from CCH might account for the establishment of vascular cognitive impairment and dementia (VCID) and Alzheimer’s disease (AD). However, the complex and multifactorial etiology of cerebrovascular disease demands the combination of experimental models in scientific research. In this sense, the present work aims at summarizing the differential available rodent paradigms for studying the establishment of cognitive decline resulting from protein misfolding induced by MetS in association with CCH. Revising experimental findings in the field will help further basic research on the pathophysiology of cerebrovascular disease and the future testing of protein-remodeling factors as neuroprotective agents for the prevention of cognitive impairment
Palmitoylethanolamide Ameliorates Hippocampal Damage and Behavioral Dysfunction After Perinatal Asphyxia in the Immature Rat Brain
Abstract: Perinatal asphyxia (PA) is an obstetric complication associated with an impaired gas exchange. This health problem continues to be a determinant of neonatal mortality and neurodevelopmental disorders. Palmitoylethanolamide (PEA) has exerted neuroprotection in several models of brain injury and neurodegeneration. We aimed at evaluating the potential neuroprotective role of PEA in an experimental model, which induces PA in the immature rat brain. PA was induced by placing Sprague Dawley newborn rats in a water bath at 37°C for 19 min. Once their physiological conditions improved, they were given to surrogate mothers that had delivered normally within the last 24 h. The control group was represented by non-fostered vaginally delivered pups, mimicking the clinical situation. Treatment with PEA (10 mg/kg) was administered within the first hour of life. Modifications in the hippocampus were analyzed with conventional electron microscopy, immunohistochemistry (for NeuN, pNF-H/M, MAP-2, and GFAP) and western blot (for pNF H/M, MAP-2, and GFAP). Behavior was also studied throughout Open Field (OF) Test, Passive Avoidance (PA) Task and Elevated Plus Maze (EPM) Test. After 1 month of the PA insult, we observed neuronal nucleus degeneration in CA1 using electron microscopy. Immunohistochemistry revealed a significant increase in pNF-H/M and decrease in MAP-2 in CA1 reactive area. These changes were also observed when analyzing the level of expression of these markers by western blot. Vertical exploration impairments and anxiety-related behaviors were encountered in the OF and EPM tests. PEA treatment attenuated PA-induced hippocampal damage and its corresponding behavioral alterations. These results contribute to the elucidation of PEA neuroprotective role after PA and the future establishment of therapeutic strategies for the developing brain.Fil: Herrera, María I. Universidad Católica Argentina. Facultad de Psicología y Psicopedagogía. Centro de Investigaciones en Psicología y Psicopedagogía; ArgentinaFil: Udovin, Lucas Daniel. Universidad de Buenos Aires. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Udovin, Lucas Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Toro-Urrego, Nicolás. Universidad de Buenos Aires. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Toro-Urrego, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Kusnier, Carlos. Universidad de Buenos Aires. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Kusnier, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Luaces, Juan P. Universidad de Buenos Aires. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Luaces, Juan P. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Capani, Francisco. Universidad de Buenos Aires. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Capani, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Capani, Francisco. Universidad Católica Argentina. Facultad de Medicina; ArgentinaFil: Capani, Francisco. Universidad Autónoma de Chile; Chil
Spermatogenesis is seasonal in the large hairy armadillo, Chaetophractus villosus (Dasypodidae, Xenarthra, Mammalia)
Palmitoylethanolamide Ameliorates Hippocampal Damage and Behavioral Dysfunction After Perinatal Asphyxia in the Immature Rat Brain
Perinatal asphyxia (PA) is an obstetric complication associated with an impaired gas exchange. This health problem continues to be a determinant of neonatal mortality and neurodevelopmental disorders. Palmitoylethanolamide (PEA) has exerted neuroprotection in several models of brain injury and neurodegeneration. We aimed at evaluating the potential neuroprotective role of PEA in an experimental model, which induces PA in the immature rat brain. PA was induced by placing Sprague Dawley newborn rats in a water bath at 37°C for 19 min. Once their physiological conditions improved, they were given to surrogate mothers that had delivered normally within the last 24 h. The control group was represented by non-fostered vaginally delivered pups, mimicking the clinical situation. Treatment with PEA (10 mg/kg) was administered within the first hour of life. Modifications in the hippocampus were analyzed with conventional electron microscopy, immunohistochemistry (for NeuN, pNF-H/M, MAP-2, and GFAP) and western blot (for pNF H/M, MAP-2, and GFAP). Behavior was also studied throughout Open Field (OF) Test, Passive Avoidance (PA) Task and Elevated Plus Maze (EPM) Test. After 1 month of the PA insult, we observed neuronal nucleus degeneration in CA1 using electron microscopy. Immunohistochemistry revealed a significant increase in pNF-H/M and decrease in MAP-2 in CA1 reactive area. These changes were also observed when analyzing the level of expression of these markers by western blot. Vertical exploration impairments and anxiety-related behaviors were encountered in the OF and EPM tests. PEA treatment attenuated PA-induced hippocampal damage and its corresponding behavioral alterations. These results contribute to the elucidation of PEA neuroprotective role after PA and the future establishment of therapeutic strategies for the developing brain
Palmitoylethanolamide attenuates neurodevelopmental delay and early hippocampal damage following perinatal asphyxia in rats
Impaired gas exchange close to labor causes perinatal asphyxia (PA), a
neurodevelopmental impairment factor. Palmitoylethanolamide (PEA) proved
neuroprotective in experimental brain injury and neurodegeneration models.
This study aimed to evaluate PEA effects on the immature-brain, i.e., early
neuroprotection by PEA in an experimental PA paradigm. Newborn rats were
placed in a 37◦C water bath for 19 min to induce PA. PEA 10 mg/kg, s.c.,
was administered within the first hour of life. Neurobehavioral responses were
assessed from postnatal day 1 (P1) to postnatal day 21 (P21), recording the day
of appearance of several reflexes and neurological signs. Hippocampal CA1
area ultrastructure was examined using electron microscopy. Microtubuleassociated protein 2 (MAP-2), phosphorylated high and medium molecular
weight neurofilaments (pNF H/M), and glial fibrillary acidic protein (GFAP)
were assessed using immunohistochemistry and Western blot at P21. Over
the first 3 weeks of life, PA rats showed late gait, negative geotaxis and
eye-opening onset, and delayed appearance of air-righting, auditory startle,
sensory eyelid, forelimb placing, and grasp reflexes. On P21, the hippocampal
CA1 area showed signs of neuronal degeneration and MAP-2 deficit. PEA
treatment reduced PA-induced hippocampal damage and normalized the
time of appearance of gait, air-righting, placing, and grasp reflexes. The
outcome of this study might prove useful in designing intervention strategies
to reduce early neurodevelopmental delay following PA..
Neuroprotection Targeting Protein Misfolding on Chronic Cerebral Hypoperfusion in the Context of Metabolic Syndrome
Metabolic syndrome (MetS) is a cluster of risk factors that lead to microvascular dysfunction and chronic cerebral hypoperfusion (CCH). Long-standing reduction in oxygen and energy supply leads to brain hypoxia and protein misfolding, thereby linking CCH to Alzheimer's disease. Protein misfolding results in neurodegeneration as revealed by studying different experimental models of CCH. Regulating proteostasis network through pathways like the unfolded protein response (UPR), the ubiquitin-proteasome system (UPS), chaperone-mediated autophagy (CMA), and macroautophagy emerges as a novel target for neuroprotection. Lipoxin A4 methyl ester, baclofen, URB597, N-stearoyl-L-tyrosine, and melatonin may pose potential neuroprotective agents for rebalancing the proteostasis network under CCH. Autophagy is one of the most studied pathways of proteostatic cell response against the decrease in blood supply to the brain though the role of the UPR-specific chaperones and the UPS system in CCH deserves further research. Pharmacotherapy targeting misfolded proteins at different stages in the proteostatic pathway might be promising in treating cognitive impairment following CCH