Search Results (161)

Traumatic brain injury (TBI) is being increasingly recognized as a major risk factor for chronic neurodegenerative disease, including chronic traumatic encephalopathy (CTE) and Alzheimer’s disease (AD). Biomechanical forces during head trauma, particularly rotational acceleration and angular deformation, produce diffuse axonal injury (DAI) and widespread white matter damage that trigger persistent neurobiological cascades. These include axonal transport failure, blood–brain barrier (BBB) disruption, neuroinflammation, neurovascular and mitochondrial dysfunction, and pathological protein aggregation, closely paralleling core AD features. Epidemiological data support a dose–response relationship between TBI severity or repetition and subsequent dementia risk, moderated by genetic factors such as apolipoprotein E4 (ApoE4). Converging experimental and early clinical studies have begun to target shared injury and neurodegenerative pathways through acute neuroprotection, stem cell-based strategies for BBB restoration and neural repair, transcriptional and hormonal modulation, mitochondrial stabilization, and immunomodulation of chronic inflammation. This review synthesizes evidence linking biomechanical injury to molecular and neurovascular pathways of neurodegeneration and summarizes emerging temporally targeted interventions. By integrating mechanistic and therapeutic perspectives, we aim to narrow the translational gap between TBI and AD, refine identification of at-risk populations, and inform priorities for prevention and development of disease-modifying therapies. Full article

Background/Objectives: Cerebral angiography is a cornerstone diagnostic and therapeutic procedure for cerebrovascular diseases; however, its potential effects on vascular integrity and cellular homeostasis remain incompletely elucidated. This systematic review aims to comprehensively evaluate endothelial and histopathological alterations induced by cerebral angiographic procedures, with particular emphasis on oxidative stress, inflammation, endothelial dysfunction, and blood–brain barrier disruption. Methods: This systematic review was conducted in accordance with the PRISMA 2020 guidelines. PubMed, Scopus, and Web of Science databases were systematically searched for studies published between 1981 and 2025 using predefined keywords related to cerebral angiography, endothelial injury, oxidative stress, inflammation, and histopathological changes. A total of 1142 records were identified, and 216 duplicates were removed. Following title and abstract screening, 312 full-text articles were assessed for eligibility, of which 112 were excluded due to irrelevance or insufficient endothelial or histopathological data. Ultimately, 200 studies were included in the qualitative synthesis. The literature identification, screening, and selection process are summarized in the manuscript. The review protocol was not prospectively registered. Results: The included studies demonstrated that cerebral angiographic procedures induce endothelial and microvascular alterations through both mechanical and contrast-mediated mechanisms. Iodinated contrast agents were consistently associated with increased reactive oxygen species production, reduced endothelial nitric oxide bioavailability, mitochondrial dysfunction, and activation of pro-inflammatory signaling pathways, including nuclear factor kappa B (NF-κB). Histopathological findings revealed endothelial swelling, vacuolization, apoptosis, microthrombus formation, inflammatory cell infiltration, and disruption of endothelial junctions, leading to increased vascular permeability and blood–brain barrier impairment. Mechanical factors related to catheter manipulation and high-pressure contrast injection further exacerbated endothelial injury by altering shear stress and promoting leukocyte adhesion. The severity of endothelial damage and inflammatory responses was consistently greater in patients with comorbid conditions such as diabetes mellitus, hypertension, and atherosclerotic disease. Conclusions: Cerebral angiography may induce endothelial dysfunction and histopathological vascular injury predominantly through oxidative and inflammatory mechanisms. Optimization of contrast agent selection, refinement of procedural techniques, and implementation of endothelial-protective strategies may mitigate vascular injury and improve procedural safety. Further translational and clinical studies are warranted to identify biomarkers and protective interventions targeting angiography-induced endothelial damage. Full article

This review explores the interplay between SARS-CoV-2 and HIV-1 infections within the human brain, highlighting the significant neurological implications of these viral infections. SARS-CoV-2 can infect the central nervous system (CNS), with evidence of the virus detected in various brain regions, including the hypothalamus, cerebellum, and olfactory bulb. This infection is linked to microglial activation and neuroinflammation, which can lead to severe neurological outcomes in affected individuals. Autopsy studies revealed microglial changes, including downregulation of the P2RY12 receptor, indicating a shift from homeostatic to inflammatory phenotype. Similar changes in microglia are found in the brains of people with HIV-1 (PWH). In SARS-CoV-2, the correlation between inflammatory cytokines, such as IL-1, IL-6, and MCP-1, found in cerebrospinal fluid and brain tissues, indicates significant neurovascular inflammation. Astrogliosis and microglial nodules were observed, further emphasizing the inflammatory response triggered by the viral infections, again in parallel to those found in the brains of PWH. Epidemiologic data indicate that although SARS-CoV-2 infection rates in PWH mirror those in People without HIV (PWoH) populations, Long-COVID prevalence is markedly higher among PWH. Evidence of overlapping cognitive impairment, mental health burden, and persistent neuroinflammation highlights diagnostic complexity and therapeutic gaps. Despite plausible mechanistic synergy, direct neuropathological confirmation remains scarce, warranting longitudinal, biomarker-driven studies. Understanding these interactions is critical for developing targeted interventions to mitigate CNS injury and improve outcomes. Full article

Numerous studies report cognitive impairment in COVID-19 patients from the acute to post-acute phases, linked to blood inflammation affecting blood–brain barrier (BBB) permeability and causing leakage of glial and neuronal proteins. However, a clear classification of these cognitive deficits and molecular blood events over time is still lacking. This narrative review summarizes the neuropsychological consequences of COVID-19 and evidence of altered cytokines and BBB disruption as potential mediators of cognitive impairment across post-infection phases. Post-COVID-19 cognitive dysfunction appears to follow a temporal course, evolving from acute focal deficits in attention, working memory, and executive function to more persistent multidomain impairments. We reviewed key cytokines released into the blood during COVID-19 infection, including antiviral (IFNγ, CXCL1, CXCL10), inflammatory (IL-1β, IL-2, IL-4, IL-6, IL-7, IL-8, IL-10, GM-CSF, TNFα), and monocyte chemoattractants (MCP1/CCL2, MCP3/CCL7, MIP-1α/CCL3, GM-CSF, G-CSF). This analysis shows that several inflammatory and viral cytokines remain elevated beyond the acute phase and are associated with cognitive deficits, including IL-6, IL-13, IL-8, IL-1β, TNFα, and MCP1 in long-term post-COVID-19 patients. In addition, we examined studies analyzing changes over time in neurovascular unit proteins as biomarkers of BBB disruption, including extracellular matrix proteins (PPIA, MMP-9), astrocytes (S100β, GFAP), and neurons (NFL). These proteins are elevated in acute COVID-19 but generally return to control levels within six months, suggesting BBB restoration. However, in patients followed for over a year, BBB disruption persists only in those with cognitive impairment and is associated with systemic inflammation, with TGFβ as a related biomarker. Although cognitive sequelae can persist for over 12 months after SARS-CoV-2 infection, further studies are needed to investigate long-term neurocognitive outcomes and their link to sustained proinflammatory cytokine elevation and brain impact. Full article

Cognitive deterioration and the transition to neurodegenerative disease does not develop through simple, linear regression; it develops as rapid and global transitions from one state to another within the neural network. Developing understanding and control over these events is among the largest tasks facing contemporary neuroscience. This paper will discuss a conceptual reframing of cognitive decline as a transitional phase of the functional state of complex neural networks resulting from the intertwining of molecular degradation, vascular dysfunction and systemic disarray. The paper will integrate the latest findings that have demonstrated how the disruptive changes in glymphatic clearance mechanisms, aquaporin-4 polarity, venous output, and neuroimmune signaling increasingly correlate with the neurophysiologic homeostasis landscape, ultimately leading to the destabilization of the network attraction sites of memory, consciousness, and cognitive resilience. Furthermore, the destabilizing processes are exacerbated by epigenetic silencing; neurovascular decoupling; remodeling of the extracellular matrix; and metabolic collapse that result in accelerating the trajectory of neural circuits towards the pathological tipping point of various neurodegenerative diseases including Alzheimer’s disease; Parkinson’s disease; traumatic brain injury; and intracranial hypertension. New paradigms in systems neuroscience (connectomics; network neuroscience; and critical transition theory) provide an intellectual toolkit to describe and predict these state changes at the systems level. With artificial intelligence and machine learning combined with single cell multi-omics; radiogenomic profiling; and digital twin modeling, the predictive biomarkers and early warnings of impending collapse of the system are beginning to emerge. In terms of therapeutic intervention, the possibility of reprogramming the circuitry of the brain into stable attractor states using precision neurointervention (CRISPR-based neural circuit reprogramming; RNA guided modulation of transcription; lineage switching of glia to neurons; and adaptive neuromodulation) represents an opportunity to prevent further progression of neurodegenerative disease. The paper will address the ethical and regulatory implications of this revolutionary technology, e.g., algorithmic transparency; genomic and other structural safety; and equity of access to advanced neurointervention. We do not intend to present a list of the many vertices through which the mechanisms listed above instigate, exacerbate, or maintain the neurodegenerative disease state. Instead, we aim to present a unified model where the phenomena of molecular pathology; circuit behavior; and computational intelligence converge in describing cognitive decline as a translatable change of state, rather than an irreversible succumbing to degeneration. Thus, we provide a framework for precision neurointervention, regenerative brain medicine, and adaptive intervention, to modulate the trajectory of neurodegeneration. Full article

Major depressive disorder (MDD) is a complex and heterogeneous psychiatric condition with high global prevalence and significant personal and societal burdens. While traditionally focused on neuronal dysfunction, emerging research highlights a critical role for astrocytes—glial cells essential for maintaining brain homeostasis in the pathogenesis of depression. This review explores how chronic stress, a major risk factor for MDD, disrupts astrocyte function through multiple converging mechanisms. We detail the normal physiological roles of astrocytes in synaptic regulation, neurotransmitter cycling, metabolic support, and neurovascular integrity, and examine how these functions are compromised under chronic stress. Key molecular pathways implicated include glucocorticoid receptor (GR) signaling dysregulation, neuroinflammatory responses, glutamate excitotoxicity, oxidative stress, and epigenetic alterations. Evidence from histological and transcriptomic studies in both human postmortem tissue and rodent models reveals consistent changes in astrocyte-specific genes, such as GFAP, SLC1A2, SLC1A3, BDNF, and AQP4, supporting their involvement in depressive pathology. Finally, we discuss therapeutic strategies targeting astrocyte dysfunction—including EAAT2 upregulation, neuromodulation, anti-inflammatory approaches, GR modulation, and glial-focused epigenetic therapies. Understanding astrocyte pathology in the context of chronic stress not only refines our understanding of MDD but also opens novel avenues for treatment development. Full article

The way in which Aquaporin-4 (AQP4) is localized on the astrocytes’ surface—i.e., with AQP4 channels predominantly located on the endfeet of astrocytes near the blood vessels—represents an important structural element for maintaining brain fluid homeostasis. In addition to this structural function, AQP4 polarity also facilitates glymphatic transport, the maintenance of the blood–brain barrier (BBB) functions, ion buffering, and neurotransmitter removal, and helps regulate neurovascular communications. The growing body of literature suggests that the loss of AQP4 polarity—a loss in the organization of AQP4 channels to the perivascular membrane—is associated with increased vascular, inflammatory, and metabolic disturbances in the context of many neurological diseases. As a result, this review attempts to synthesize both experimental and clinical studies to highlight that AQP4 depolarization often occurs in conjunction with early signs of neurodegeneration and neuroinflammation; however, we are aware that the loss of AQP4 polarity is only one factor in a complex pathophysiological environment. This review examines the molecular structure responsible for maintaining the polarity of AQP4—such as dystrophin–syntrophin complexes, orthogonal particle arrays, lipid microdomains, trafficking pathways, and transcriptional regulators—and describes how the vulnerability of these systems to various types of vascular stress, inflammatory signals, energy deficits, and mechanical injury can lead to a loss of AQP4 polarity. Furthermore, we will explore how a loss of AQP4 polarity can lead to the disruption of perivascular fluid movement, changes in blood–brain barrier morphology, enhanced neuroimmune activity, changes in ionic and metabolic balance, and disruptions in the global neural network synchronization. Importantly, we recognize that each of these disruptions will likely occur in concert with other disease-specific mechanisms. Alterations in AQP4 polarity have been observed in a variety of neurological disorders including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, traumatic brain injury, and glioma; however, we also observe that the same alterations in fluid regulation occur across all of these different diseases, but that no single upstream event accounts for the alteration in polarity. Ultimately, we will outline emerging therapeutic avenues to restore perivascular fluid transport, and will include molecular-based therapeutic agents designed to modify the anchoring of AQP4, methods designed to modulate the state of astrocytes, biomaterials-based drug delivery systems, and therapeutic methods that leverage dynamic modulation of the neurovascular interface. Future advances in multi-omic profiling, spatial proteomics, glymphatic imaging, and artificial intelligence will allow for earlier identification of AQP4 polarity disturbances and potentially allow for the development of more personalized treatment plans. Ultimately, by linking these concepts together, this review aims to frame AQP4 polarity as a modifiable aspect of the “fluidic connectome”, and highlight its importance in maintaining overall brain health across disease states. Full article

Post-occlusive reactive hyperemia (PORH) is widely used to assess microvascular reactivity, but its systemic impact on contralateral neurovascular function remains unclear. This study quantified bilateral synchrony and asymmetry of cutaneous signals during unilateral PORH in healthy subjects using a novel multidimensional framework of inter-limb coherence. Twelve young adults underwent a standard suprasystolic occlusion (5 min at 200 mmHg) on the upper limb, while photoplethysmography (PPG), skin temperature, and electrodermal activity (EDA) were recorded bilaterally in the fingers. Coherence was characterized by profile similarity (Cross-Signal Similarity Index, CSSI), temporal lag (τ*), magnitude asymmetry (Bilateral Magnitude Difference Index, BDMI), directional concordance (Signal Direction Index, SDI; Directional Concordance Index, DCI), and integrated indices (IBIL, IBIS). At baseline, all signals showed high bilateral synchrony (CSSI ≈ 0.9; τ* < 20 ms). Occlusion markedly reduced CSSI for blood flow (0.89 to 0.07, p = 0.002) and temperature (0.93 to −0.03, p = 0.06), while EDA coherence remained preserved (0.95 to 0.82). Integrated indices decreased significantly (IBIL 0.84 to 0.17, p = 0.005; IBIS 0.84 to 0.18, p = 0.004) and recovered only partially during hyperemia (IBIL 0.20, p = 0.003). Directional concordance was heterogeneous: during hyperemia, 9 of 12 subjects showed concordant EDA changes but only 7 of 12 for perfusion. BDMI was largest for perfusion (≈0.8), moderate for temperature (≈0.5), and minimal for EDA (≈0.3). Unilateral PORH thus induces a marked loss of bilateral coherence in microvascular signals, whereas sympathetic-driven responses remain strongly synchronized. This dissociation reveals that occlusion evokes systemic autonomic adjustments beyond local hemodynamics. The proposed framework captures hidden aspects of neurovascular integration and may provide new markers for autonomic imbalance or perfusion asymmetry. Full article

Background and Objectives: Dry eye disease (DED) is a multifactorial ocular surface disease that markedly diminishes quality of life. Although diabetes mellitus is well-known for its retinal consequences, anterior segment symptoms including dry eye disease are often overlooked. Chronic hyperglycemia causes metabolic, neurovascular, and immunological changes that undermine tear film stability, corneal innervation, and ocular surface integrity. This review seeks to consolidate existing knowledge regarding the concealed impacts of diabetes on ocular surface homeostasis, highlighting processes, diagnostic difficulties, and treatment prospects. Materials and Methods: A narrative review of the literature was performed by searching PubMed for publications from January 2020 to July 2025 using the terms “diabetic dry eye,” “hyperglycemia AND ocular surface,” “tear proteomics AND diabetes,” “corneal nerves AND diabetes,” and “neurotrophic keratitis.” Eligible studies were experimental research, clinical trials, and translational investigations concerning tear film function, corneal neuropathy, inflammatory indicators, or lacrimal gland dysfunction in diabetes. The exclusion criteria were non-English language, lack of primary data, and inadequate methodological description. Results: Hyperglycemia compromises lacrimal gland functionality, modifies lipid secretion from Meibomian glands, and diminishes corneal nerve density, resulting in neurotrophic deficits. Inflammatory cytokines and oxidative stress compromise epithelial integrity, but proteome alterations in tears serve as sensitive indicators of disease. Diagnosis is impeded by corneal hypoesthesia, resulting in a disconnection between symptoms and findings. Progress in imaging, proteomics, and artificial intelligence may facilitate earlier detection and improved risk assessment. Novel therapeutics, such as neurotrophic drugs, antioxidants, and customized anti-inflammatory approaches, show promise but remain under clinical evaluation. Conclusions: Diabetes-related dry eye disease is a multifaceted and underappreciated condition influenced by systemic metabolic dysfunction. The ocular surface may act as an initial indicator for systemic disease load. Narrative synthesis emphasizes the necessity for customized diagnostic instruments, individualized treatment approaches, and collaborative management. Reconceptualizing diabetic dry eye disease within the context of systemic metabolic care presents prospects for precision medicine strategies that enhance both ocular and systemic results. Full article

Background/Objectives: The Kocher–Langenbeck approach is widely used for surgical fixation of posterior acetabular wall fractures. While previous studies have focused on mechanical outcomes and the risk of post-traumatic osteoarthritis, the effects on peripheral circulation and neuromuscular recovery remain underexplored. This study aimed to evaluate dynamic changes in neuromuscular function and microcirculation following open reduction and internal fixation (ORIF) using this approach. Methods: A retrospective analysis was conducted on 34 patients (aged 23–75) treated for posterior acetabular wall fractures between 2014 and 2022. All patients underwent ORIF via the Kocher–Langenbeck approach. Assessments at 8 and 12 months postoperatively included electromyography (EMG), chronaximetry, and rheovasography (RVG). Asymmetry coefficients were calculated to quantify blood flow and functional differences. Results: At 12 months postoperatively, significant microcirculatory asymmetry persisted in the operated limb, with arterial and venous coefficients exceeding 25% (27.5% and 26.8%, respectively). EMG revealed sustained reductions in gluteus maximus and rectus femoris activity (asymmetry ~39%). Chronaximetry showed delayed nerve conduction recovery, particularly in the common peroneal nerve (AC = 44%). The femoral segment demonstrated the most severe impairment in both arterial inflow and venous outflow. Conclusions: ORIF via the Kocher–Langenbeck approach is associated with long-term disturbances in neuromuscular function and regional circulation. Further research should explore alternative surgical approaches (e.g., ilioinguinal, Stoppa) in prospective studies, assess vascular integrity using advanced imaging (e.g., contrast-enhanced ultrasound), and incorporate long-term functional outcomes. Studies on neurovascular-sparing techniques and optimised rehabilitation protocols may help reduce postoperative morbidity and improve recovery. Full article

Prediabetes is an intermediate stage between normoglycaemia and type 2 diabetes mellitus (T2DM), affecting over 425 million people globally and contributing to vascular damage and increased stroke risk. Despite the severity of both conditions, their association remains underexplored. This review examines the literature on stroke-related biomarkers in normoglycaemia, prediabetes and T2DM to identify potential links between prediabetes and stroke. This systematic review followed PRISMA-2020 guidelines. PubMed, Google Scholar, Scopus, Web of Science and Science Direct were searched for studies (2003–2023) on stroke biomarkers in prediabetes. Eligible studies were original human research in English, with defined diagnostic criteria (ADA or WHO) for glycaemic status and reported biomarker associations or stroke risk. Studies with major comorbidities were excluded. Data were extracted and bias was assessed using the Newcastle–Ottawa Scale. Meta-analysis was not performed due to limited studies per biomarker. Eight studies (n = 3003) were included. NSE was examined in three studies, all reporting significant elevations in hyperglycaemic individuals. Interleukin-6 (IL-6) was assessed in two studies; one showed a significant increase in diabetes, while the other found a non-significant upward trend. D-dimer and GFAP were each reported in separate single studies, both showing significant elevations in hyperglycaemic individuals with stroke or neurocognitive impairment. S100B was investigated in two studies, with divergent findings: one showed a positive association with glycaemic status, while the other reported lower levels in hyperglycaemia. Findings indicate biomarker alterations in T2DM, suggesting that early changes may occur in prediabetes. Our review suggests that individuals with prediabetes may show alterations in inflammatory (IL-6), coagulation (D-dimer), and neurovascular (S100B, GFAP, NSE) markers, though some findings are inconsistent, reflecting early pathophysiological changes that may increase stroke risk. Further well-designed studies are needed to clarify these associations and establish biomarker-based tools for earlier stroke risk detection and prevention in individuals with prediabetes. Full article

Retinal vasculature is essential for maintaining visual function by supporting metabolically active neurons. However, the retina lacks redundant blood supply, rendering it highly susceptible to vascular dysfunction. Understanding mechanisms of retinal vascular abnormalities is critical for therapies that preserve vascular and neuronal integrity, yet progress has been hindered by limited models and genetic diversity. To address this gap, we examined the retinal vasculature in multiple aged strains from the BXD recombinant inbred mouse panel, a genetically diverse, tractable, and physiologically relevant platform for uncovering novel genetic drivers and disease mechanisms. We identified BXD32 as a striking outlier with dramatically reduced vessel density. Using optical coherence tomography, optical coherence tomography angiography, and histological analyses, we comprehensively characterized retinal vasculature and structural integrity of BXD32 mice during aging. We found progressive, age-dependent vascular dysfunction and degeneration, beginning in the deep capillary plexus and advancing to the intermediate and superficial layers. These changes were accompanied by neuronal degeneration, including photoreceptor loss and thinning of the ganglion cell complex. Our findings establish BXD32 as a spontaneous and genetically tractable model of inherited retinal neurovascular degeneration and provide a foundation for future studies to identify causative genetic loci and underlying molecular mechanisms. Full article

Traumatic brain injury (TBI) is a major global health concern and a leading cause of long-term disability and mortality. While the primary mechanical insult is often the focus of acute care, secondary injury mechanisms—particularly cerebrovascular dysfunction—play a critical role in ongoing neural damage and poor outcomes. Increasing research highlights the role of neurovascular changes in TBI pathophysiology. This narrative review compiles evidence from the past decade on mechanisms, diagnostic methods, and treatments related to cerebrovascular dysfunction after TBI. A structured search of PubMed and Embase identified relevant clinical and preclinical studies. Key mechanisms include blood–brain barrier disruption, impaired cerebral autoregulation, microthrombosis, and oxidative stress. Diagnostic tools discussed include perfusion imaging, cerebrovascular reactivity testing, and blood-based biomarkers of vascular injury. Therapeutic strategies targeting the neurovascular unit are categorized by mechanism: anti-inflammatory agents (e.g., celecoxib, minocycline), mitochondrial protectors (e.g., Tanshinone IIA), and vasomodulators (e.g., sildenafil). We propose an integrated therapeutic approach for a multimodal treatment plan that integrates these interventions. The findings emphasize the importance of patient-specific vascular therapies to reduce secondary ischemic injury and enhance neurological recovery. Although promising preclinical data exist, clinical application remains limited. More well-designed trials are needed to confirm the safety and effectiveness of emerging therapies. Full article

Pharmacotherapy in the geriatric population is one of the greatest challenges in modern medicine. Elderly patients, characterized by multimorbidity and the resulting polypharmacy, are significantly more exposed to adverse drug reactions (ADRs), which often lead to hospitalization and a decline in quality of life. Understanding the reasons for this difference requires an analysis of the physiological changes that occur during the aging process at the molecular level. This article presents a perspective on the molecular aspects of geriatric pharmacotherapy, focusing on the fundamental mechanisms that are modified with age. The analysis covers changes in pharmacokinetics, including the role and regulation of cytochrome P450 (CYP) enzymes, whose activity, especially in phase I reactions, is significantly reduced. The age-dependent dysfunction of drug transporters from the ABC (ATP-binding cassette) and SLC (solute carrier) families in key organs such as the intestines, liver and kidneys is discussed, which affects the absorption, distribution and elimination of xenobiotic compounds, including drugs. The article also provides a comprehensive analysis of the blood–brain barrier (BBB), describing changes in neurovascular integrity, including the dysfunction of tight junctions and a decrease in the activity of P-glycoprotein, sometimes referred to as multidrug resistance protein (MDR). This increases the susceptibility of the central nervous system to the penetration and action of drugs. In the realm of pharmacodynamics, changes in the density and sensitivity of key receptors (serotonergic, dopaminergic, adrenergic) are described based on neuroimaging data, explaining the molecular basis for increased sensitivity to certain drug classes, such as anticholinergics. The paper also explores new research perspectives, such as the role of the gut microbiome in modulating pharmacokinetics by influencing gene expression and the importance of pharmacoepigenetics, which dynamically regulates drug response throughout life via changes in DNA methylation and histone modifications. The clinical implications of these molecular changes are also discussed, emphasizing the potential of personalized medicine, including pharmacogenomics, in optimizing therapy and minimizing the risk of adverse reactions. Such an integrated approach, incorporating data from multiple fields (genomics, epigenomics, microbiomics) combined with a comprehensive geriatric assessment, appears to be the future of safe and effective pharmacotherapy in the aging population. Full article

Peripheral nerve injuries (PNIs) are common and often result in sensorimotor deficits, chronic pain and decreased quality of life. While the peripheral nervous system has greater regenerative capacity than the central nervous system, recovery is often limited by intrinsic changes in the nerve and muscle. This review summarizes the process of nerve regeneration, with a focus on the role of the vasculature, following PNI and examines current bioengineering approaches to enhance peripheral nerve regeneration through modification of the nerve microenvironment and optimization of neurovascular interactions. The primary areas of translational research discussed in this review include vascularized nerve grafts, nerve conduits and scaffolds, bioactive peptides, nanoparticles, extracellular vesicles, stem cells, and gene therapy. Full article