Iron chelator deferiprone rescues memory deficits, hippocampal BDNF levels and antioxidant defenses in an experimental model of memory impairment.

Brain-derived neurotrophic factor (BDNF) plays a key role in neural development and physiology, as well as in pathological states. Post-mortem studies demonstrate that BDNF is reduced in the brains of patients affected by neurodegenerative diseases. Iron accumulation has also been associated to the pathogenesis of neurodegenerative diseases. In rats, iron overload induces persistent memory deficits, increases oxidative stress and apoptotic markers, and decreases the expression of the synaptic marker, synaptophysin. Deferiprone (DFP) is an oral iron chelator used for the treatment of systemic iron overload disorders, and has recently been tested for Parkinson's disease. Here, we investigated the effects of iron overload on BDNF levels and on mRNA expression of genes encoding TrkB, p75NTR, catalase (CAT) and NQO1. We also aimed at investigating the effects of DFP on iron-induced impairments. Rats received iron or vehicle at postnatal days 12-14 and when adults, received chronic DFP or water (vehicle). Recognition memory was tested 19 days after the beginning of chelation therapy. BDNF measurements and expression analyses in the hippocampus were performed 24 h after the last day of DFP treatment. DFP restored memory and increased hippocampal BDNF levels, ameliorating iron-induced effects. Iron overload in the neonatal period reduced, while treatment with DFP was able to rescue, the expression of antioxidant enzymes CAT and NQO1.

G protein-coupled oestrogen receptor stimulation ameliorates iron- and ovariectomy-induced memory impairments through the cAMP/PKA/CREB signalling pathway.

Iron accumulation in the brain has been associated with neurodegenerative disorders, and imaging studies in humans indicate that iron content in brain regions correlates with poor performance in cognitive tasks. In rats, iron overload impairs memory retention in a variety of memory tasks. Although the effects of iron on cognition in rodents are extensively reported, no previous study has been conducted in female rats. The incidence of certain dementias, such as Alzheimer's disease, is higher in women after menopause compared to aged-matched men. The role of oestrogen depletion in memory deficits in menopausal women is still a matter of debate. The present study aimed to characterise the effects of iron overload on memory in female rats by investigating the effects of ovariectomy (OVX, an experimental model of oestrogen depletion) in rats submitted to iron overload, as well as examining the effects of G protein-coupled oestrogen receptor (GPER) agonism on memory impairments induced by iron and OVX. Female rats received iron (30 mg kg-1 , orally) or vehicle at postnatal days 12-14 and were submitted to OVX in adulthood. Results showed that either iron or OVX impaired memory for object placement and inhibitory avoidance. The selective GPER agonist G1, administered immediately after training, reversed both iron- and OVX-induced memory impairments. G1 effects were abolished by protein kinase A (PKA) inhibition, suggesting the involvement of the cAMP/PKA/CREB signalling pathway. The search for novel oestrogen agonists with positive effects on cognition may be promising for the development of treatments for memory disorders.

Atualização na reanimação volêmica no paciente traumatizado / Update on volemic resuscitation in trauma patient

Introdução: O choque hipovolêmico é o principal tipo de choque no trauma. Seu manejo é fundamental visto que é uma das principais causas de mortes evitáveis. Objetivos: Definir conceitos relacionados à reanimação no choque hipovolêmico, como coagulopatia precoce no trauma, controle de danos, hipotensão permissiva, uso de cristaloides e hemoderivados, ácido tranexâmico e protocolo de transfusão maciça. Metodologia: Busca na base de dados bibliográfica Medline/Pubmed e LILACS no período de maio de 2018, incluindo artigos de revisão, revisões sistemáticas e guidelines cuja publicação seja em inglês ou português e remeta os últimos 5 anos. Os descritores foram "permissive hypotension" ou "damage control resuscitation". "hypovolemic shock". Os artigos foram selecionados com busca direta, considerando relevância do tema à proposta e revista com fator de impacto mensurado. Resultados: Foram apresentados 342 resultados da busca de dados, nos quais 15 artigos foram selecionados. Na conduta do choque hipovolêmico, responsável por 30 a 40% das mortes no período de 24 horas após o trauma, adota-se a hipotensão permissiva e preconiza-se o controle de danos. Conclusões: O entendimento da coagulopatia no trauma, do uso limitado de cristaloides, da reanimação balanceada, da hipotensão permissiva, da correta indicação do ácido tranexâmico e da aplicação do protocolo de transfusão maciça é fundamental na reanimação volêmica do paciente traumatizado.

Introduction: The hypovolemic shock is the main type of shock in trauma patients. Its management is fundamental given that hemorrhagic shock is one of the main causes of death that can be avoided. Aims: To define concepts related to resuscitation in hypovolemic shock, such as early coagulopathy in trauma, damage control, permissive hypotension, use of crystalloids and blood derivatives, tranexamic acid and massive transfusion protocol. Methods: Search in the bibliographic database Medline/Pubmed and LILACS in the period of May 2018, including review articles, systematic reviews and guidelines published in either English or Portuguese in the last 5 years. The descriptors were "permissive hypotension" or "damage control resuscitation". Of the 342 results, 15 articles were selected with direct search, considering relevance of the theme to the proposal and reviewed with measured impact factor. Results: From 342 results in database, 10 articles have been selected. The management of hypovolemic shock, responsible for 30-40% of deaths within 24 hours of trauma, permissive hypotension and damage control have been recommended. Conclusion: The understanding of coagulopathy in trauma, of limited use of crystalloids, of balanced resuscitation, of permissive hypotension, of the correct indication of tranexamic acid and of the application of the protocol of massive transfusion is essential in the resuscitation of the trauma patient.