Sophia Konovalova

Biomaterials for neural tissue engineering, cell delivery, and chronic neural interfaces are conventionally characterized through physicochemical descriptors such as stiffness, topography, surface chemistry, and degradation rate. However, their biological effects are mediated by the material–tissue interface, which evolves through protein adsorption, extracellular matrix ligand presentation, and progressive cellular remodeling and determines how these design parameters are translated into neuronal and glial responses. This review synthesizes current evidence on how neurons, astrocytes, and microglia sense the material–tissue interface, how integrin-dependent adhesion complexes, mechanosensitive Piezo1 channels, and downstream FAK/Src, RhoA/ROCK, and YAP/TAZ pathways transduce interfacial cues into intracellular signaling, and how key design variables (mechanical properties, architecture, surface chemistry, electrical conductivity, and degradation) can be tuned to direct these processes in regenerative scaffolds and chronic neural interfaces. Particular attention is given to studies distinguishing direct neuronal effects from glia-mediated modulation, since concurrent changes in neuronal and glial markers are often reported without establishing causal neuron–glia interaction. We further discuss methodological limitations that constrain current interpretations of biomaterial-induced neuron–glia crosstalk, including discrepancies between 2D, 3D, and in vivo models and insufficient durations of chronic observation. We argue that functional biomaterial design for neural applications should move from optimizing isolated cellular readouts toward multicellular experimental frameworks capable of resolving neuron–glia–ECM interactions over physiologically relevant timescales.

Background: Lipid nanoparticles (LNPs) can activate innate immunity, but the factors shaping repeat-dose reactogenicity remain unclear. We compared systemic, local, and organ-specific reactions after intramuscular administrations of empty LNPs containing ionizable lipids used in mRNA vaccines. Methods: Female BALB/c mice received two intramuscular injections, 2 weeks apart, of LNP-4 (four components, ALC-0315 as the sole ionizable lipid; 59 nm) or LNP-5 (five components, equimolar ALC-0315/SM-102 at the same total ionizable lipid content; 86 nm). Body weight was monitored for 15 days. Blood biochemical parameters, injection-site histology, and morphological and molecular markers in the hypothalamus, liver, lungs, and spleen were assessed 24 h after the second injection by histology, immunohistochemistry (IHC), immunofluorescence (IF), Western blotting, and quantitative PCR (qPCR). Results: Both LNPs were followed by transient body-weight loss, moderate biochemical changes, and local reactogenicity. The strongest organ-specific responses occurred in the liver and hypothalamus. Both LNPs induced hepatic sinusoidal dilation and leukocyte infiltration, but LNP-4 was associated with more myeloid cell numbers and higher inflammatory marker expression. In the hypothalamus, LNP-4 produced broader changes in inflammatory and myeloid marker expression than LNP-5. No marked structural damage was observed in the examined organs. Conclusions: Repeated LNP administration was followed by systemic and local reactogenicity, and organ-specific changes differed between the formulations, possibly reflecting lipid composition, particle size, and lipid dose. Carrier composition should be considered in the design and safety evaluation of LNP-based vaccine delivery systems.

Biomaterials for neural tissue engineering, cell delivery, and chronic neural interfaces are conventionally characterized through physicochemical descriptors such as stiffness, topography, surface chemistry, and degradation rate. However, their biological effect is mediated by the material–tissue interface, a dynamic layer formed through protein adsorption, extracellular matrix ligand presentation, and progressive cellular remodeling, that determines how these design parameters are translated into neuronal and glial responses. This review synthesizes current evidence on how neurons, astrocytes, and microglia sense the material–tissue interface, how integrin-dependent adhesion complexes, mechanosensitive Piezo1 channels, and downstream FAK/Src, RhoA/ROCK, and YAP/TAZ pathways transduce interfacial cues into intracellular signaling, and how key design variables (mechanical properties, architecture, surface chemistry, electrical conductivity, and degradation) can be tuned to direct these processes in regenerative scaffolds and chronic neural interfaces. Particular attention is given to studies distinguishing direct neuronal effects from glia-mediated modulation, since concurrent changes in neuronal and glial markers are often reported without establishing causal neuron–glia interaction. We further discuss methodological limitations, including model mismatch across 2D, 3D, and in vivo systems and insufficient duration of chronic observation, that constrain current interpretations of biomaterial-induced neuron–glia crosstalk. We argue that functional biomaterial design for neural applications should move from optimizing isolated cellular readouts toward multicellular experimental frameworks capable of resolving neuron–glia–ECM interactions over physiologically relevant timescales.

Spinal cord injury (SCI) leads to severe disability in patients, and one of the key obstacles to the recovery of lost functions is inefficient axonal remyelination. The high sensitivity of oligodendrocytes to secondary damage, the formation of a glial scar, and chronic neuroinflammation sustained by pro-inflammatory/neurotoxic microglia create a physical and chemical barrier to neuroplasticity processes. This review summarizes current knowledge on the ability of the serotonergic system to modulate the functional state of the main types of glial cells: oligodendrocytes, astrocytes, and microglia. It is shown that oligodendrocyte precursor cells (OPCs) and mature oligodendrocytes express 5-HT_1A, 5-HT_2A, and 5-HT₇ receptors, whose activation can either stimulate differentiation or suppress migration or induce apoptosis, depending on the developmental stage and microenvironment. In astrocytes, serotonin, predominantly via 5-HT_2B receptors, limits pro-inflammatory transformation, reduces NLRP3 inflammasome activity, and stimulates BDNF production, glycogenolysis, and lactate release. In microglia, serotonergic stimulation (via 5-HT_1A, 5-HT_2A, 5-HT_2B, and 5-HT₇ receptors) attenuates the pro-inflammatory phenotype by suppressing production of TNF-α and IL-1β. To date, the proposed therapeutic strategies include: the use of 5-HT receptor agonists/antagonists and transplantation of serotonergic cells (hNT2.19 and RN46A-B14 lines), which reduce neuropathic pain and promote motor function recovery in rodents after SCI. The key limitations for the effective translation of these findings into clinical practice are the heterogeneity of effects of different serotonin receptor subtypes, the dependence of outcomes on the time after injury, and pronounced species specificity. Thus, the serotonergic system represents a promising but complex target for inducing neuroplasticity processes; success requires the development of subtype-selective ligands and treatment protocols that take into account the stages of pathological processes in SCI.

Spinal cord injury (SCI) remains a major clinical challenge due to the limited regenerative capacity of the central nervous system (CNS). Effective scaffolds for repair must combine mechanical compatibility with host tissue, controlled degradation matching the time course of regeneration, and microarchitectural features that promote neuronal survival. Electrospun nanofibrous scaffolds mimic the structural and mechanical features of the extracellular matrix, providing critical cues for neuronal adhesion and glial modulation in neural regeneration. Here, we fabricated biodegradable poly(lactic acid)/poly(ε-caprolactone) (PLA/PCL) scaffolds using a dichloromethane/tetrahydrofuran (DCM/THF) solvent system to induce surface porosity via solvent-driven phase separation. The DCM/THF solvent system formulation produced nanofibers with porous surfaces and increased area for cell interaction. PLA/PCL scaffolds showed a Young’s modulus of ~26 MPa and sustained degradation, particularly under oxidative conditions simulating the post-injury microenvironment. In vitro, these scaffolds enhanced neuronal density up to fivefold and maintained ~80% viability over 10 days in primary neuron–glia cultures. Morphometric analysis revealed that DCM/THF-based scaffolds supported astrocytes with preserved process complexity and reduced circularity, indicative of a less reactive morphology. In contrast, scaffolds fabricated with 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) displayed reduced bioactivity and promoted morphological features associated with astrocyte reactivity, including cell rounding and process retraction. These findings demonstrate that solvent-driven control of scaffold microarchitecture is a powerful strategy to enhance neuronal integration and modulate glial morphology, positioning DCM/THF-processed PLA/PCL scaffolds as a promising platform for CNS tissue engineering.

Objective: Spinal cord injury (SCI) is a debilitating condition that not only affects motor and sensory functions, but also causes widespread neuroplastic and neuroinflammatory changes in the hippocampus, a brain region critical for learning and memory. Methods: This study examined region-specific changes in hippocampal subregions (CA1, CA3, and dentate gyrus) in a rat model of SCI, evaluating neurogenesis, microglial and astroglial cell activation, and behavioral outcomes. Results and Discussion: The study revealed distinct patterns of neuroplastic and neuroinflammatory changes in hippocampal subregions, with some areas showing increased susceptibility to injury-induced changes. Behavioral analyses showed a significant correlation between these hippocampal changes and impairments in memory and learning ability, highlighting the functional consequences of SCI on cognitive processes. Conclusions: The findings emphasize the importance of understanding the relationship between neuroplasticity and neuroinflammation in the hippocampus after SCI, which may facilitate the development of targeted therapeutic strategies to mitigate cognitive deficits.

Neuroinflammation plays a critical role in the pathogenesis of most neurological and neurodegenerative diseases and therefore represents a potential therapeutic target. In this regard, accelerating the resolution process in chronic neuroinflammation may be an effective strategy to deal with the cognitive consequences of neuropathology and generalized inflammatory processes. N-acylethanolamine (NAE) derivatives of fatty acids, being highly active lipid mediators, possess pro-resolving activity in inflammatory processes and are promising agents for the suppression of neuroinflammation and its consequences. This paper is devoted to a study of the effects played by dietary supplement (DS), containing a composition of fatty acid-derived NAEs, obtained from squid Berryteuthis magister, on the hippocampal neuroinflammatory and memory processes. By detecting the production of pro-inflammatory cytokines and glial markers, a pronounced anti-inflammatory activity of DS was demonstrated both in vitro and in vivo. DS administration reversed the LPS-induced reduction in hippocampal neurogenesis and memory deterioration. LC-MS analysis revealed an increase in the production of a range of NAEs with well-documented anti-inflammatory activity in response to the administered lipid composition. To conclude, we found that tested DS suppresses the neuroinflammatory response by reducing glial activation, positively regulates neural progenitor proliferation, and attenuates hippocampal-dependent memory impairment.

Neuropathic pain arises from damage or dysfunction of the peripheral or central nervous system and manifests itself in a wide variety of sensory symptoms and cognitive disorders. Many studies demonstrate the role of neuropathic pain-induced neuroinflammation in behavioral disorders. For effective neuropathic pain treatment, an integrative approach is required, which simultaneously affects several links of pathogenesis. One promising candidate for this role is synaptamide (N-docosahexaenoylethanolamine), which is an endogenous metabolite of docosahexaenoic acid. In this study, we investigated the activity of synaptamide on mice behavior and hippocampal plasticity in neuropathic pain induced by spared nerve injury (SNI). We found a beneficial effect of synaptamide on the thermal allodynia and mechanical hyperalgesia dynamics. Synaptamide prevented working and long-term memory impairment. These results are probably based on the supportive effect of synaptamide on SNI-impaired hippocampal plasticity. Nerve ligation caused microglia activation predominantly in the contralateral hippocampus, while synaptamide inhibited this effect. The treatment reversed dendritic tree degeneration, dendritic spines density reduction on CA1-pyramidal neurons, neurogenesis deterioration, and hippocampal long-term potentiation (LTP) impairment. In addition, synaptamide inhibits changes in the glutamatergic receptor expression. Thus, synaptamide has a beneficial effect on hippocampal functioning, including synaptic plasticity and hippocampus-dependent cognitive processes in neuropathic pain.

The present study demonstrates that synaptamide (N-docosahexaenoylethanolamine), an endogenous metabolite of docosahexaenoic acid, when administered subcutaneously (4 mg/kg/day, 14 days), exhibits analgesic activity and promotes cognitive recovery in the rat sciatic nerve chronic constriction injury (CCI) model. We analyzed the dynamics of GFAP-positive astroglia and S100β-positive astroglia activity, the expression of nerve growth factor (NGF), and two subunits of the NMDA receptor (NMDAR1 and NMDAR2A) in the hippocampi of the experimental animals. Hippocampal neurogenesis was evaluated by immunohistochemical detection of DCX. Analysis of N-acylethanolamines in plasma and in the brain was performed using the liquid chromatography-mass spectrometry technique. In vitro and in vivo experiments show that synaptamide (1) reduces cold allodynia, (2) improves working memory and locomotor activity, (3) stabilizes neurogenesis and astroglial activity, (4) enhances the expression of NGF and NMDAR1, (5) increases the concentration of Ca²⁺ in astrocytes, and (6) increases the production of N-acylethanolamines. The results of the present study demonstrate that synaptamide affects the activity of hippocampal astroglia, resulting in faster recovery after CCI.

The search for methods of cognitive impairment treatment and prevention in neurological and neurodegenerative diseases is an urgent task of modern neurobiology. It is now known that various diseases, accompanied by dementia, exhibit a pronounced neuroinflammation. Considering the significant docosahexaenoic and eicosapentaenoic polyunsaturated fatty acids’ therapeutic potential, we decided to investigate and compare anti-inflammatory activity of their N-acylethanolamine derivatives. As a result, we found that both N-docosahexaenoylethanolamine (synaptamide) and N-eicosapentaenoylethanolamine (EPEA) prevents an LPS-mediated increase in the proinflammatory cytokines TNF-α and IL-6 production in the SIM-A9 microglia culture. In an in vivo experiment, synaptamide reversed an increase in LPS-mediated hippocampal TNF-α and IL-1β, but EPEA did not. However, both compounds contributed to the microglia polarization towards the M2-phenotype. Synaptamide, rather than EPEA, inhibited the Iba-1-positive microglia staining area increase. However, both synaptamide and EPEA prevented the LPS-mediated astrogliosis. A study of BDNF immunoreactivity showed that synaptamide, but not EPEA, reversed an LPS-mediated decrease in BDNF production. Despite the more pronounced anti-inflammatory activity of synaptamide, both compounds were effective in maintaining a normal level of hippocampal long-term potentiation in neuroinflammation. The results indicate a high therapeutic potential for both compounds. However, some tests have shown higher activity of synaptamide compared to EPEA.