Future Neurology 

About: Future Neurology is an academic journal published by Future Medicine. The journal publishes majorly in the area(s): Stroke & Epilepsy. It has an ISSN identifier of 1479-6708. It is also open access. Over the lifetime, 840 publications have been published receiving 7847 citations.

Microglia in ischemic brain injury.

Abstract: Microglia are resident CNS immune cells that are active sensors in healthy brain and versatile effectors under pathological conditions. Cerebral ischemia induces a robust neuroinflammatory response that includes marked changes in the gene-expression profile and phenotype of a variety of endogenous CNS cell types (astrocytes, neurons and microglia), as well as an influx of leukocytic cells (neutrophils, macrophages and T-cells) from the periphery. Many molecules and conditions can trigger a transformation of surveying microglia to microglia of an alerted or reactive state. Here we review recent developments in the literature that relate to microglial activation in the experimental setting of in vitro and in vivo ischemia. We also present new data from our own laboratory demonstrating the direct effects of in vitro ischemic conditions on the microglial phenotype and genomic profile. In particular, we focus on the role of specific molecular signaling systems, such as hypoxia inducible factor-1 and Toll-like receptor-4, in regulating the microglial response in this setting. We then review histological and novel radiological data that confirm a key role for microglial activation in the setting of ischemic stroke in humans. We also discuss recent progress in the pharmacologic and molecular targeting of microglia in acute ischemic stroke. Finally, we explore how recent studies on ischemic preconditioning have increased interest in pre-emptively targeting microglial activation in order to reduce stroke severity.

From singing to speaking: facilitating recovery from nonfluent aphasia

Abstract: It has been reported for more than 100 years that patients with severe nonfluent aphasia are better at singing lyrics than they are at speaking the same words. This observation led to the development of melodic intonation therapy (MIT). However, the efficacy of this therapy has yet to be substantiated in a randomized controlled trial. Furthermore, its underlying neural mechanisms remain unclear. The two unique components of MIT are the intonation of words and simple phrases using a melodic contour that follows the prosody of speech and the rhythmic tapping of the left hand that accompanies the production of each syllable and serves as a catalyst for fluency. Research has shown that both components are capable of engaging fronto-temporal regions in the right hemisphere, thereby making MIT particularly well suited for patients with large left hemisphere lesions who also suffer from nonfluent aphasia. Recovery from aphasia can happen in two ways: either through the recruitment of perilesional brain regions in the affected hemisphere, with variable recruitment of right-hemispheric regions if the lesion is small, or through the recruitment of homologous language and speech-motor regions in the unaffected hemisphere if the lesion of the affected hemisphere is extensive. Treatment-associated neural changes in patients undergoing MIT indicate that the unique engagement of right-hemispheric structures (e.g., the superior temporal lobe, primary sensorimotor, premotor and inferior frontal gyrus regions) and changes in the connections across these brain regions may be responsible for its therapeutic effect.

Autophagy in neuroprotection and neurodegeneration: a question of balance

Abstract: A central issue in developing therapies for neurodegenerative diseases involves understanding why adaptive responses to stress or injury fail to prevent synaptic dysfunction and neuronal cell death Macroautophagy is a major, evolutionarily conserved response to nutrient and bioenergetic stresses, which has the capacity to remove aggregated proteins and damaged organelles such as mitochondria This has prompted intense interest in autophagy-related therapies for Huntington's, Alzheimer's, Parkinson's, stroke and other neurological diseases However, excessive or imbalanced induction of autophagic recycling can actively contribute to neuronal atrophy, neurite degeneration and cell death Oxidative-, aging- and disease-related increase in demand for autophagy, coupled with declining axonal trafficking, lysosomal degradation or biosynthetic efficiencies promote increased susceptibility to a harmful state of autophagic stress A more complete understanding of dysfunction along the entire spectrum of autophagic recycling, from autophagosome formation through clearance and regeneration of new cellular components is necessary to restore balance to the system, promote neuronal health and maximize therapeutic potentials

Metacognition, self-reflection and recovery in schizophrenia

Abstract: Metacognition reflects a spectrum of activities that includes discrete acts in which persons form ideas about specific thoughts and feelings, and synthetic acts in which persons integrate discrete thoughts and feelings into complex representations of themselves and others. This article reviews literature suggesting that persons with schizophrenia and related psychosis experience deficits across the spectrum of metacognitive activities and that these deficits play a key role in dysfunction, often mediating and moderating the impact of symptoms and social adversity on daily life. Treatment approaches including metacognitive training and adaptations of psychotherapy are still in their infancy. Future work is needed to study the etiology of deficits in discrete and synthetic metacognition, as well as their overlap with related constructs such as mentalization and social cognition.

Neurobiology of dysregulated motivational systems in drug addiction

Abstract: The progression from recreational drug use to drug addiction impacts multiple neurobiological processes and can be conceptualized as a transition from positive to negative reinforcement mechanisms driving both drug-taking and drug-seeking behaviors. Neurobiological mechanisms for negative reinforcement, defined as drug taking that alleviates a negative emotional state, involve changes in the brain reward system and recruitment of brain stress (or antireward) systems within forebrain structures, including the extended amygdala. These systems are hypothesized to be dysregulated by excessive drug intake and to contribute to allostatic changes in reinforcement mechanisms associated with addiction. Points of intersection between positive and negative motivational circuitry may further drive the compulsivity of drug addiction but also provide a rich neurobiological substrate for therapeutic intervention.