Abstract Locomotor impairment is one of the most devastating consequences of spinal cord injury (SCI) and cannot be adequately overcome by existing rehabilitation methods. Numerous studies in spinalized mammals have demonstrated that serotonin, dopamine, and noradrenaline receptors located on spinal cord cells below the injury level play an important role in locomotor recovery. Hence, these monoamine receptors (MARs) represent promising targets for pharmacological rehabilitation following SCI, but no drug targeting them has yet proven sufficiently effective for locomotor recovery or reached clinical use. This review summarizes current data on the spinal localization of MARs, their postinjury changes (expression and function), and the role of specific receptor subtypes and their combinations in regulating kinematic, kinetic, and electromyographic locomotor parameters in intact and spinalized mammals. Specifically, the studies reviewed here show that some MARs are important for locomotor control in healthy animals, while the role of others becomes apparent only after SCI. Data on changes in receptor expression following SCI are contradictory and strongly depend on the experimental protocol, animal species, and sex, as well as on the type of sample analyzed. Finally, targeting different receptor subtypes affects distinct locomotor parameters, whereas simultaneous targeting of multiple receptors (e.g., 5-HT1AR + 5-HT2A/2CR + D1R + α2AR) can produce a synergistic effect. Therefore, the development of highly selective drugs and knowledge of post-traumatic changes occurring in receptors will enable targeting of a narrow spectrum of receptors and correction of individual locomotor parameters depending on the degree of their impairment.
Abstract Perioperative neurocognitive disorders (PND) are clinically important complications in older surgical patients, but broad neuroinflammatory models do not fully explain age-related susceptibility or failed recovery. Aging alters microglial surveillance, phagocytosis, mitochondrial function, lipid handling, and inflammatory thresholds before surgery. This mechanism-focused narrative review, informed by a structured literature search, examines impaired microglial lipid handling as an interface between brain aging and perioperative cognitive vulnerability. Evidence is organized along three axes: lipid sensing, uptake, and storage; lipid catabolism and polyunsaturated fatty acid (PUFA) remodeling; and lipid-redox injury with downstream synaptic and circuit dysfunction. Direct perioperative support is strongest for age-associated microglial activation, immune modulation through triggering receptor expressed on myeloid cells 2 (TREM2), fatty acid desaturase 1 (FADS1)-dependent lipid remodeling, and neuronal or astrocytic ferroptosis-related injury. In contrast, microglial lipid catabolism mediated by multifunctional enzyme type 2 (MFE-2), apolipoprotein E4 (APOE4)-associated triglyceride metabolism, and TREM2-dependent lipid-droplet regulation are supported mainly by aging, neurodegeneration, or ischemic injury studies. Separating clinical and preclinical perioperative findings from nonperioperative mechanisms defines a testable lipid-neuroimmune framework for causal experiments, biomarker development, and mechanism-guided intervention.
Because of their involvement in outbreaks, hantaviruses as emerging zoonotic diseases have been regarded a public health issue. Recent reports have identified CNS symptoms of hantavirus infection, although the data are still relatively sparse and inconsistent, especially for Andes orthohantavirus (ANDV) and to a lesser extent Puumala virus (PUUV). Reported neurological features include headache, dizziness, altered mental state, seizures, focal deficits, and peripheral neuropathy, possibly accompanied by ocular symptoms such as impaired vision and photophobia. The results of neuroimaging have been inconsistent and nonspecific, ranging from hemorrhagic or edematous changes to thalamic or brainstem abnormalities and splenial lesions. Evidence could suggest that endothelial dysfunction, capillary leak, inflammatory damage, and, in certain situations, potential intrathecal immunological responses or direct viral presence may all contribute to CNS involvement. However, most evidence stems from case reports or case series, and causative neuroinvasion may not have been fully demonstrated. Recent studies, especially the recent ANDV-associated outbreak, may emphasize the necessity for rigorous neurological examination. A better understanding of the neurological range of hantavirus infection may enhance detection, risk stratification, and supportive therapy.
Periodic complexes occur in the electroencephalogram (EEG) during a number of pathological conditions, often having a poor prognosis (Kuroiwa and Celesia 1980). The contexts in which periodic EEGs occur generally fall into three major categories: infections, sequelae to hypoxic/ischemic events, and metabolic disorders. In this review, we examine morphological and electrophysiological data from in vitro preparations. These data suggest several cellular mechanisms, which may underlie periodic EEGs, including altered excitation-inhibition relations, tonic activation of metabotropic glutamate receptors, altered neuromodulation, and electrical coupling of neurons by cell fusion or gap junctions. Some of the proposed mechanisms are empirically testable: for example, the occurrence of very fast oscillations (>∼70 Hz) superimposed on periodic complexes, and the occurrence of gamma oscillations (∼30 Hz-∼70 Hz) between complexes. The in vitro data further suggest an hypothesis concerning why some patients with periodic EEGs respond to anticonvulsant drugs (ACDs), while other patients do not: if the main cellular mechanism for neuronal synchrony involves excitatory chemical synapses, then a response to ACDs is possible; however, if a major factor in neuronal synchrony involves electrical coupling - as can occur with viral infections - then a response to ACDs would not be expected.
Aneurysmal subarachnoid hemorrhage (aSAH) confers substantial mortality and morbidity driven not only by primary brain injury but also by systemic remote organ complications across the pulmonary, cardiac, renal and gastrointestinal systems. Despite growing recognition of neuroimmune crosstalk in this process, a cohesive, systems-level model connecting intracranial hemorrhage to multi-organ dysfunction remains absent from the literature. Here, we propose a unified neuroimmune framework centered on a long-underappreciated mechanism: glymphatic and meningeal lymphatic drainage dysfunction is hypothesized to act as the upstream initiating event that forces brain-derived damage-associated molecular patterns, inflammatory cytokines and activated immune cells to spill into the systemic circulation. We systematically map three mechanistically distinct, mutually amplifying transmission pathways: the classical neuroendocrine-immune axis, the recently identified meningeal lymphatic-deep cervical lymph node immune drainage axis, and circulating humoral effectors exemplified by neutrophil extracellular traps. Most notably, we integrate these pathways with a temporally stratified immune continuum spanning early hyperinflammatory SIRS, stroke-induced immunodepression, and chronic low-grade inflammation - an integrative temporal architecture that has eluded prior single-organ or single-pathway studies. Grounded in this framework, we put forward a tiered, phase-specific neuroimmunomodulatory strategy that simultaneously addresses central inflammatory origins, systemic signal propagation, and end-organ tissue damage. By reframing remote organ injury as a time-dependent immune process rather than a collection of isolated organ complications, this work provides a mechanistic and translational roadmap for time-stratified clinical trials and redefines the investigative direction for multi-organ management in aSAH.
