Band 32, Heft 5

Astrocytes play a major role in brain function and alterations in astrocyte function that contribute to the pathogenesis of many brain disorders. The astrocytes are attractive cellular targets for neuroprotection and brain tissue regeneration. Development of novel approaches to monitor and to control astroglial function is of great importance for further progress in basic neurobiology and in clinical neurology, as well as psychiatry. Recently developed advanced optogenetic and chemogenetic techniques enable precise stimulation of astrocytes in vitro and  in vivo , which can be achieved by the expression of light-sensitive channels and receptors, or by expression of receptors exclusively activated by designer drugs. Optogenetic stimulation of astrocytes leads to dramatic changes in intracellular calcium concentrations and causes the release of gliotransmitters. Optogenetic and chemogenetic protocols for astrocyte activation aid in extracting novel information regarding the function of brain’s neurovascular unit. This review summarizes current data obtained by this approach and discusses a potential mechanistic connection between astrocyte stimulation and changes in brain physiology.

Long-term memories are thought to be stored in neurones and synapses that undergo physical changes, such as long-term potentiation (LTP), and these changes can be maintained for long periods of time. A candidate enzyme for the maintenance of LTP is protein kinase M zeta (PKMζ), a constitutively active protein kinase C isoform that is elevated during LTP and long-term memory maintenance. This paper reviews the evidence and controversies surrounding the role of PKMζ in the maintenance of long-term memory. PKMζ maintains synaptic potentiation by preventing AMPA receptor endocytosis and promoting stabilisation of dendritic spine growth. Inhibition of PKMζ, with zeta-inhibitory peptide (ZIP), can reverse LTP and impair established long-term memories. However, a deficit of memory retrieval cannot be ruled out. Furthermore, ZIP, and in high enough doses the control peptide scrambled ZIP, was recently shown to be neurotoxic, which may explain some of the effects of ZIP on memory impairment. PKMζ knockout mice show normal learning and memory. However, this is likely due to compensation by protein-kinase C iota/lambda (PKCι/λ), which is normally responsible for induction of LTP. It is not clear how, or if, this compensatory mechanism is activated under normal conditions. Future research should utilise inducible PKMζ knockdown in adult rodents to investigate whether PKMζ maintains memory in specific parts of the brain, or if it represents a global memory maintenance molecule. These insights may inform future therapeutic targets for disorders of memory loss.

Recent advances in neuroimaging have demonstrated significant assessment benefits and appropriate triage of patients based on specific clinical and radiological features in the acute stroke setting. Endovascular thrombectomy is arguably the most important aspect of acute stroke management with an extended time window. Imaging-based physiological information may potentially shift the treatment paradigm from a rigid time-based model to a more flexible and individualized, tissue-based approach, increasing the proportion of patients amenable to treatment. Various imaging modalities are routinely used in the diagnosis and management of acute ischemic stroke, including multimodal computed tomography (CT) and magnetic resonance imaging (MRI). Therefore, these imaging methods should provide information beyond the presence or absence of intracranial hemorrhage as well as the presence and extent of the ischemic core, collateral circulation and penumbra in patients with neurological symptoms. Target mismatch may optimize selection of patients with late or unknown symptom onset who would potentially be eligible for revascularization therapy. The purpose of this study was to provide a comprehensive review of the current evidence about efficacy and theoretical basis of present imaging modalities, and explores future directions for imaging in the management of acute ischemic stroke.

Spinal cord injury (SCI) is a debilitating condition which often leads to a severe disability and ultimately impact patient’s physical, psychological, and social well-being. The management of acute SCI has evolved over the couple of decades due to improved understanding of injury mechanisms and increasing knowledge of disease. Currently, the early management of acute SCI patient includes pharmacological agents, surgical intervention and newly experimental neuroprotective strategies. However, many controversial areas are still surrounding in the current treatment strategies for acute SCI, including the optimal timing of surgical intervention, early versus delayed decompression outcome benefits, the use of methylprednisolone. Due to the lack of consensus, the optimal standard of care has been varied across treatment centres. The authors have shed a light on the current updates on early treatment approaches and neuroprotective strategies in the initial management of acute SCI in order to protect the early neurologic injury and reduce the future disability.

Transient Global Amnesia (TGA) constitutes an enigmatic amnestic condition. In view of the admittedly limited knowledge regarding the nature of TGA, we decided to systematically review existing evidence for the generally regarded benign course of the disease. MEDLINE, EMBASE, CENTRAL and PsycINFO were searched for relevant articles. Observational (case-control, cross-sectional and cohort) controlled studies were retrieved. TGA diagnosis was made according to the diagnostic criteria of Caplan, validated by Hodges and Warlow. The TGA group was compared with either healthy controls (HC) or/and individuals with transient ischaemic attacks (TIA). The long-term risks of dementia, epilepsy, psychological-emotional disturbances, as well as long-term vascular and (vascular or nonvascular) mortality risks, were evaluated. Quality assessment was based on the Newcastle–Ottawa Scale. Literature search provided 12 eligible articles. Retrospective, prospective or mixed cohort designs were implemented in every study. Five articles registered a high quality, five registered a moderate quality, while two articles were assessed as part of the grey literature (conference abstract, abstract in English-article in Spanish). Overall, retrieved evidence was suggestive of similar vascular and mortality risks in TGA patients and HC, while TIA individuals exhibited elevated risks. Moreover, psychological disturbances were comparable between TGA and healthy individuals. On the other hand, studies for dementia and epilepsy obtained contradictory results, indicating both a similar and an increased risk in the TGA group compared to the HC group. Therefore, additional high-quality studies are warranted for the acquisition of more determining conclusions regarding the long-term risk of dementia and epilepsy in TGA.

Clinical therapies for chronic pain are limited. While targeted drugs are promising therapies for chronic pain, they exhibit insufficient efficacy and poor targeting. The occurrence of chronic pain partly results from central changes caused by alterations in neurons in the rostral ventromedial medulla (RVM) in the brainstem regulatory pathway. The RVM, which plays a key role in the descending pain control pathway, greatly contributes to the development and maintenance of pain. However, the exact roles of the RVM in chronic pain remain unclear, making it difficult to develop new drugs targeting the RVM and related pathways. Here, we first discuss the roles of the RVM and related circuits in chronic pain. Then, we analyze synaptic transmission between RVM neurons and spinal cord neurons, specifically focusing on the release of neurotransmitters, to explore the cellular mechanisms by which the RVM regulates chronic pain. Finally, we propose some ideas for the development of drugs targeting the RVM.

Psychedelic drugs are well-known for transiently altering perception, and in particular, for their visual effects. Although scientific interest into the substances’ effects on perception increased during the first era of psychedelic research during the early to mid-20th century, there is currently no source where these findings have been synthesized. In addressing this gap, the current narrative review found that psychedelics were examined for their influences across all levels of the visual system (e.g., retinal, cortical, subcortical, simple visual processing, complex imagery, hallucinations). Psychedelics were also shown to affect auditory discrimination/generalization, neural correlates of auditory processing, and led to auditory hallucinations in subsets of participants. Several studies demonstrated that psychedelics can distort representations of body schema and time perception. Concerns regarding methodological standards of this era are a limitation to the findings and are discussed. Collectively, this review preserves and increases the accessibility of the work done by pioneering psychedelic/perception researchers, synthesizes findings, and critically analyzes areas of discrepancy to inform future studies.