Glutamate Scavenging as a Neuroreparative Strategy in Ischemic Stroke.

Stroke is the second highest reason of death in the world and the leading cause of disability. The ischemic stroke makes up the majority of stroke cases that occur due to the blockage of blood vessels. Therapeutic applications for ischemic stroke include thrombolytic treatments that are in limited usage and only applicable to less than 10% of the total stroke patients, but there are promising new approaches. The main cause of ischemic neuronal death is glutamate excitotoxicity. There have been multiple studies focusing on neuroprotection via reduction of glutamate both in ischemic stroke and other neurodegenerative diseases that ultimately failed due to the obstacles in delivery. At that point, systemic glutamate grabbing, or scavenging is an ingenious way of decreasing glutamate levels upon ischemic stroke. The main advantage of this new therapeutic method is the scavengers working in the circulating blood so that there is no interference with the natural brain neurophysiology. In this review, we explain the molecular mechanisms of ischemic stroke, provide brief information about existing drugs and approaches, and present novel systemic glutamate scavenging methods. This review hopefully will elucidate the potential usage of the introduced therapeutic approaches in stroke patients.

Acute and Delayed Effects of Mechanical Injury on Calcium Homeostasis and Mitochondrial Potential of Primary Neuroglial Cell Culture: Potential Causal Contributions to Post-Traumatic Syndrome.

In vitro models of traumatic brain injury (TBI) help to elucidate the pathological mechanisms responsible for cell dysfunction and death. To simulate in vitro the mechanical brain trauma, primary neuroglial cultures were scratched during different periods of network formation. Fluorescence microscopy was used to measure changes in intracellular free Ca2+ concentration ([Ca2+]i) and mitochondrial potential (ΔΨm) a few minutes later and on days 3 and 7 after scratching. An increase in [Ca2+]i and a decrease in ΔΨm were observed ~10 s after the injury in cells located no further than 150-200 µm from the scratch border. Ca2+ entry into cells during mechanical damage of the primary neuroglial culture occurred predominantly through the NMDA-type glutamate ionotropic channels. MK801, an inhibitor of this type of glutamate receptor, prevented an acute increase in [Ca2+]i in 99% of neurons. Pathological changes in calcium homeostasis persisted in the primary neuroglial culture for one week after injury. Active cell migration in the scratch area occurred on day 11 after neurotrauma and was accompanied by a decrease in the ratio of live to dead cells in the areas adjacent to the injury. Immunohistochemical staining of glial fibrillary acidic protein and ß-III tubulin showed that neuronal cells migrated to the injured area earlier than glial cells, but their repair potential was insufficient for survival. Mitochondrial Ca2+ overload and a drop in ΔΨm may cause delayed neuronal death and thus play a key role in the development of the post-traumatic syndrome. Preventing prolonged ΔΨm depolarization may be a promising therapeutic approach to improve neuronal survival after traumatic brain injury.

COVID-19 and neurological sequelae: Vitamin D as a possible neuroprotective and/or neuroreparative agent.

SARS-CoV-2, the etiological agent of the current COVID-19 pandemic, belongs to a broad family of coronaviruses that also affect humans. SARS-CoV-2 infection usually leads to bilateral atypical pneumonia with significant impairment of respiratory function. However, the infectious capacity of SARS-CoV-2 is not limited to the respiratory system, but may also affect other vital organs such as the brain. The central nervous system is vulnerable to cell damage via direct invasion or indirect virus-related effects leading to a neuroinflammatory response, processes possibly associated with a decrease in the activity of angiotensin II converting enzyme (ACE2), the canonical cell-surface receptor for SARS-CoV-2. This enzyme regulates neuroprotective and neuroimmunomodulatory functions and can neutralize both inflammation and oxidative stress generated at the cellular level. Furthermore, there is evidence of an association between vitamin D deficiency and predisposition to the development of severe forms of COVID-19, with its possible neurological and neuropsychiatric sequelae: vitamin D has the ability to down-modulate the effects of neuroinflammatory cytokines, among other anti-inflammatory/immunomodulatory effects, thus attenuating harmful consequences of COVID-19. This review critically analyzes current evidence supporting the notion that vitamin D may act as a neuroprotective and neuroreparative agent against the neurological sequelae of COVID-19.

Prometeo: regeneración tisular: pifias de la naturaleza y esperanzas de la ciencia / Prometheus: tissue regeneration: natural errors and scientific hope

En el movisimo campo de las células troncales ("stem cell") y la medicina regenerativa, la búsqueda del Santo Grial de la investigación científica, es la recreacion o la inducción del renacimiento de un órgano funcional, llamese hígado, retina o riñon. En un extremo el hígado de Prometeo, de inherente capacidad para regenerarse, la demanda del órgano excede en mucho la disponibilidad de donantes. En Estados Unidos de America, 9% de los pacientes con insuficiencia hepática fallecen a la espera de un trasplante, así que la investigación en tratamientos regenerativos nunca ha tenido más fundamento y adquirido más énfasis que en estos tiempos. En el otro extremo, la retina, inexplicable olvido de la naturaleza, como otras neuronas del sistema nervioso incapaz de regenerarse a sí misma y hasta ahora, inmune a la neuroprotección y reparación después de una injuria. No obstante en un futuro no muy lejano será posible preservar y restaurar la visión en personas en las que se encuentre amenazada o se haya perdido por enfermedad o injuria del nervio óptico

In the newest field of stem cells and regenerative medicine, the quest for the Holy Grail of scientific research is the recreation or induction of rebirth of a functional organism, such as the liver, retina o kidney. At one end liver of Prometheus with its inherent capacity to regenerate, has a demand that greatly exceeds the availability of donors. In the United States of America, 9% of patients with liver failure die waiting for a transplant, so research in regenerative treatment has never had more importance or acquired greater emphasis than at this time. At the other end, the retina, inexplicable oblivion of nature, is, as other neurons of the central nervous system, unable to regenerate itself and so far, immune to neuroprotection and repair after an injury. Nevertheless, in the future it will be possible, however, to preserve and restore vision in people whose optic nerve are threatened or have been lost due to illness or injury