This study aimed to investigate the effects of Piezo1 on blood-brain barrier (BBB) integrity and brain injury in rats with focal cerebral ischemia-reperfusion (CIR) injury. BBB permeability was evaluated via Evans blue (EB) extravasation; the Zea-Longa scoring was used to evaluate neurological function impairment; the dry-wet weight was applied to detect cerebral edema; the TTC staining was employed to measure the cerebral ischemic infarction area; and the HE staining was used to observe the morphological changes of nerve cells; the expressions and distributions of target proteins were detected by Western blotting and immunohistochemistry. Our experimental results showed that the expression of Piezo1 was significantly upregulated in the cerebral microvessels of the ischemic tissue. BBB permeability significantly increased and reached its peak at 72 h of reperfusion in CIR rats. Meanwhile, the CIR rats exhibited higher neurological deficit scores, increased brain water content, expanded infarct area, and numerous necrotic regions in the ischemic brain tissue. Administration of GsMTx4 improved the above experimental indices and significantly attenuated cell damage. Additionally, we observed that the expressions of caveolin‑1 and caveolin‑2 were significantly upregulated, and the expressions of occludin, ZO‑1, and claudin‑5 were significantly downregulated in CIR rats. After administration of GsMTx4, the expression levels of the aforementioned proteins were partially restored. This study indicates that the Piezo1 inhibitor GsMTx4 can ameliorate BBB disruption and brain injury following CIR, and exert a protective effect on BBB integrity. This effect may be jointly mediated through the paracellular and transcellular pathways.
Parkinson’s disease (PD) ranks as one of the most common neurodegenerative conditions worldwide. The goal is to explore effect of methanolic leaf extracts from Celosia cristata and Callistemon citrinus on motor impairments and neurochemical changes in a reserpine-induced mouse model of Parkinsonism, offering insights into their potential symptomatic and biochemical ameliorative value. Either sex Swiss albino mice were assigned randomly to different groups (n = 5). Nine groups were created to produce a Parkinson’s disease-like state using RES at a dose 5 mg/kg intraperitoneally, with each group receiving 200 mg/kg and 400 mg/kg per oral of Celosia cristata and Callistemon citrinus methanolic leaf extracts and their combinations for five consecutive days. Behavioral tests (Open field, Actophotometer, Rotarod) and biochemical evaluations (SOD, GPx, LPO, and MAO-B) were conducted 24 h after the last administration. Data were statistically analyzed using one-way ANOVA and Dunnett’s test. Reserpine administration decreased locomotor activity, hindered motor coordination, reduced SOD and GPx levels, and elevated LPO and MAO‑B compared to controls. Celosia cristata and Callistemon citrinus methanolic leaf extracts, as well as their combination at 200 mg/kg and 400 mg/kg, ameliorated behavioral deficits, biochemical parameters, and MAO‑B alterations caused by reserpine. The combination of both plants at 400 mg/kg total dose (MCel+MCal 400) showed the greatest overall effect (P < 0.001); however, this is consistent with a total-dose effect rather than confirmed pharmacological synergism. Methanolic leaf extracts from both plants, Celosia cristata and Callistemon citrinus, along with their combinations, demonstrated significant amelioration of motor and biochemical deficits via antioxidant mechanisms, improving behavioral impairments caused by reserpine. Reduction of MAO‑B activity may reflect attenuation of oxidative stress rather than direct enzyme inhibition. These results suggest symptomatic and biochemical ameliorative promise of methanolic leaf extracts from Celosia cristata and Callistemon citrinus, indicating their appropriateness for use in PD.
Quantitative assessment of peripheral sensorimotor function via surface electrical stimulation provides essential insights into neural responses; however, standardized stimulation parameters remain poorly defined. This study aimed to characterize the strength-duration (S-D) relationship of electrical sensory, motor, and pain thresholds (EST, EMT, and EPT) across a wide range of pulse durations to identify physiological stabilization plateaus and determine the pulse durations that maximize the discrimination between threshold types. Thirty healthy volunteers underwent electrical threshold testing (ETT) on the forearm using a symmetrical biphasic current (100 Hz). Eleven randomized pulse durations (0.02–0.65 ms) were evaluated. S‑D was analysed following Weiss’s model, and discriminative capacity was assessed using effect-size analysis. All thresholds exhibited the characteristic hyperbolic decay of the S‑D curve, although stabilization dynamics could not be determined within the pulse duration range evaluated. Thresholds were well fitted by Weiss’s linear model (R2 > 0.902), and the estimated rheobase resulted ∼0.7 mA for EST, ∼2 mA for EMT, and ∼3.7 mA for EPT. The corresponding chronaxie values were 1.09 ms for EST, 0.57 ms for EMT, and 0.41 ms for EPT. Extreme pulse durations (0.02 and 0.65 ms) demonstrated the highest discriminative capacity between thresholds (η2p = 0.936 and 0.921), although all pulse durations obtained large effect sizes (η2p > 0.869). These findings demonstrate that electrical thresholds follow a predictable neurophysiological pattern across pulse durations and suggest that pulse duration selection may be important for achieving target threshold responses, providing a reference framework for standardizing ETT protocols in both research and clinical diagnosis.
This review provides a comprehensive examination of the pivotal roles of mitogen-activated protein kinase (MAPK) signaling pathways in the pathophysiology of the blood-brain barrier (BBB). The BBB, which is essential for central nervous system homeostasis, is intricately regulated by MAPK family members—including extracellular signal-regulated kinases (ERK1/2), c‑Jun N‑terminal kinases (JNK), and p38 MAPKs—which modulate endothelial permeability, tight junction integrity, and inflammatory responses. Dysregulation of these pathways significantly compromises BBB integrity by affecting brain endothelial cells, disrupting tight junction organization, altering cytoskeletal dynamics, and increasing matrix metalloproteinase activity. Furthermore, complex crosstalk among pericytes, astrocytes, and microglia—together with oxidative stress—exacerbates BBB dysfunction, promoting inflammation, apoptosis, and autophagy. Experimental evidence from in vitro and in vivo models consistently demonstrates that aberrant MAPK activation increases BBB permeability and drives neuroinflammation, often in association with oxidative stress and degradation of tight junction proteins. Although human studies remain largely correlative, they support these findings by linking dysregulated p38 and JNK signaling to neurological disorders such as Alzheimer’s disease and ischemic stroke. Despite methodological challenges—particularly the limited specificity of MAPK inhibitors and species-related differences—MAPK pathways remain promising therapeutic targets. However, critical barriers such as insufficient brain penetrance and off-targets effects must be addressed. Future research should prioritize precision medicine approaches that consider the spatiotemporal dynamics of MAPK isoform activation and leverage advanced experimental models to develop highly selective, BBB-protective strategies. Such advances will be essential for translating mechanistic insights into effective clinical interventions for neurological diseases.
Alzheimer’s disease (AD) is the leading type of dementia, characterized by the gradual worsening of memory, disruption in synaptic communication, and progressive death of nerve cells. Pathological hallmarks of AD include the accumulation of amyloid‑β plaques, abnormal hyperphosphorylation of tau protein, increased oxidative stress, and persistent neuroinflammation. These factors collectively contribute to the initiation and advancement of the disease. Among the cellular signaling pathways involved, the nuclear factor erythroid 2‑related factor 2 (Nrf-2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways serve as major regulators, with Nrf‑2 chiefly controlling oxidative stress and NF-κB primarily managing inflammatory responses. These pathways work in dynamic balance to modulate cellular defense mechanisms. Disruption in this balance can contribute to disease pathology by increasing oxidative damage and neuroinflammation. Sinigrin is a naturally occurring glucosinolate predominantly found in cruciferous vegetables like broccoli and brussel sprouts. Preclinical studies indicate that Sinigrin regulates the Nrf-2/NF-κB signaling axis in a dual manner. Activation of Nrf‑2 by Sinigrin leads to an increased production of protective antioxidant enzymes such as heme oxygenase‑1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1), which helps to diminish oxidative stress. Sinigrin simultaneously blocks the activation of NF-κB, which results in the decreased production of pro-inflammatory cytokines like TNF‑α, IL-1β, and IL‑6. This review emphasizes the therapeutic importance of Sinigrin in AD, with a special focus on its ability to modulate the interplay between the Nrf‑2 and NF-κB signaling pathways. This dual action helps protect brain cells from damage and supports overall neural health.
Migraine is a common and chronic neurological disorder, and its diagnosis is based on the criteria of the International Classification of Headache Disorders (ICHD). However, delays in the accurate diagnosis of migraine may occur due to similar symptoms; this can negatively impact both the patient’s quality of life and healthcare economics. The aim of this study is to develop an approach that contributes to artificial intelligence-based migraine diagnostic systems by analyzing electroencephalography (EEG) signals obtained from migraine patients. In the proposed study, two distinct datasets were used, consisting of EEG signals from migraine patients and a healthy control group with similar characteristics. The EEG signals were analyzed in their raw form and were decomposed into sub-bands using adaptive signal processing methods such as Robust Local Mean Decomposition (RLMD), Circular Single-Spectrum Analysis (CiSSA), and Variational Mode Decomposition (VMD). The time-domain, frequency-domain, nonlinear, and statistical distribution features obtained from the analysis that positively influence classification performance were identified using the Least Absolute Shrinkage and Selection Operator (LASSO) feature selection method. Using the identified features, an artificial neural network (ANN), a support vector machine (SVM), and a random forest (RF) were trained to classify migraine patients and the healthy control group. According to the analysis results, the band power feature had a significant effect in distinguishing between the migraine and healthy groups in the C4 and F7 channels. The RLMD method yielded the most successful results in classification using ANN, SVM, and RF, with an mean accuracy rate of 94.58
Chronic pain is a pervasive global health challenge with complex pathophysiology involving neuro-immune crosstalk and sustained neuroinflammation. MicroRNAs (miRNAs) have emerged as pivotal epigenetic regulators in this process. This narrative review aims to systematically elucidate the mechanistic roles of specific miRNAs in various chronic pain states and synthesize recent advances in miRNA-based therapeutic and diagnostic strategies. We conducted a comprehensive narrative review of the literature, synthesizing findings from preclinical and clinical studies published primarily between 2019 and 2025 that investigate the expression, targets, and functions of miRNAs in neuropathic, inflammatory, and cancer-induced pain models. Specific miRNAs are critically involved in chronic pain by regulating targets such as ion channels (e.g., Nav1.8, TRPV1), inflammatory mediators (e.g., HMGB1, TRAF6), and epigenetic enzymes (e.g., TET1, DNMT3a). These interactions modulate key processes including synaptic plasticity, central sensitization, and glial cell activation. Furthermore, novel strategies such as targeted nanodelivery systems for miRNA mimics/inhibitors and the utilization of circulating miRNAs as biomarkers show significant therapeutic and diagnostic potential. miRNAs are central regulators of chronic pain pathogenesis. Targeting specific miRNAs holds promise for developing novel analgesics and diagnostic tools. However, challenges regarding targeted delivery, off-target effects, and clinical translation remain to be addressed for the successful application of miRNA-based medicine in pain management.
In this study, we examined the neurophysiological correlates of visual memory performance in individuals living in frontline regions of Ukraine, where prolonged exposure to environmental stress places a significant burden on adaptive processes. The aim of the study was to examine the features of the relationship between EEG power spectral density in the θ‑ and β‑bands and visual memory accuracy, as well as subgroup-specific patterns related to sex and levels of subjectively perceived stress under chronic stress conditions. The sample comprised 80 men and 80 women with low to moderate perceived stress, as assessed by the Perceived Stress Scale (PSS-10). EEG spectral power in the beta (β) and theta (θ) frequency bands was analyzed in relation to visual memory accuracy using linear regression models. The results revealed sex-specific patterns in the topographic organization of EEG-performance relationships. Under low perceived stress, the associations were mostly positive, relatively stable, and confined to specific regions, with the models explaining a larger portion of the variance. Under moderate stress, the relationships became more heterogeneous, individual variability increased, and the models explained less variance. In men, moderate stress was associated with a shift in frontal regions from positive to negative associations, while positive relationships became more prominent in parietal areas, forming a clear anterior-posterior gradient. In women, under moderate stress, θ-band associations became more prominent, while β-band associations showed redistribution, characterized by negative relationships in frontal regions and positive associations along the central-posterior midline. Rather than reflecting a uniform increase or decrease in performance, these findings indicate that stress is associated with a reorganization of the spatial and functional structure of brain-behavior relationships. The results further suggest that the strength, direction, and stability of these associations may vary according to sex and perceived stress level.
To investigate the clinical relevance of upper limb somatosensory evoked potential (SEP) status in assessing concurrent and short-term predictive relationships with functional outcomes in patients with subacute stroke. Retrospective observational study using mixed-effects modeling. Inpatient rehabilitation unit at a university-affiliated tertiary hospital. A total of 111 patients with subacute stroke who underwent upper limb SEP testing and completed functional assessments at admission and discharge. Upper limb SEP responses were categorized as non-responsive, abnormal, or normal. Functional outcomes included the Fugl-Meyer assessment for upper limb (FMA-U/L), box and block test (BBT), Functional Independence Measure (FIM), and Korean modified Barthel index (K-MBI). Mixed-effects models were used to examine both cross-sectional associations at admission and longitudinal changes over time, adjusting for age, sex, and cognitive function (K-MMSE). Patients with abnormal or normal SEP responses had significantly higher FMA-U/L, FIM, and K‑MBI scores at admission compared to those with non-responsive SEP, indicating concurrent associations between SEP integrity and functional capacity. In longitudinal analysis, these groups also showed significantly greater improvement, with the largest effect sizes observed for ADL outcomes. SEP normal status consistently showed the strongest associations across all functional domains. Cognitive function was a significant predictor in most models, while sex and age showed variable effects. Upper limb SEP status at admission is a significant marker of both baseline functional status and short-term recovery potential in patients with subacute stroke. SEP evaluation may provide clinically meaningful insights for understanding sensory pathway integrity and for short-term prognosis and to support neurophysiologically informed rehabilitation planning.
Chronic constriction injury (CCI) is a well-established experimental model used to study neuropathic pain, and herbal plants and their derivatives play a critical role in modern drug development. One such plant, Potentilla reptans L. root (PR), is known for its antioxidant and anti-inflammatory properties, represents a promising natural product for alleviating neuropathic pain. This study investigates the neuroprotective effects of PR extract on neuropathic pain induced by CCI in rats. In this study, Nociceptive behavior was quantitatively evaluated using cold allodynia and thermal hyperalgesia assays, histopathological changes in the dorsal horn of the spinal cord were examined using H E staining, and oxidative stress factors (MDA, SOD, GPX, TAC), inflammation markers (IL1‑B, TNF-α), and liver enzymes (ALT, AST) were measured. The results demonstrated that PR treatment significantly alleviated pain hypersensitivity, reduced oxidative stress and inflammatory markers and decreased neuronal damage, indicating that PR exhibits neuroprotective properties by attenuating CCI-induced injury.
The cricket terminal abdominal ganglion (TAG) serves as an experimental model analogous to the mammalian spinal cord for studying sensorimotor integration. However, further insights into the resting-state (RS) discharge of interneurons and projecting neurons are required to establish a functional model to test lesion-induced changes and potential therapies. In this study, adult male crickets were used for in situ TAG extracellular recordings under intact and RS conditions. Individual spikes were sorted for interspike interval (ISI), burst, autocorrelation, auto-spectral, and fractal analyses. Data from 131 interneurons indicated stable discharge patterns: 79.4
Autism spectrum disorders (ASD) include a complex set of behavioral disabilities stemming from genetic and environmental factors, such as prenatal exposure to valproic acid (VPA). Autism impacts social and cognitive domains, with varying severity and symptoms depending on age and individual differences. The study examined the effects of environmental stress, such as maternal deprivation, and VPA administration on learning and memory in autistic rats. Eight groups of animals were studied (male and female separately): 0.9
In this review, we have aimed at presenting the functions and function disorders of dopaminergic and serotoninergic pathways in the brain, leading to neurodegeneration. Based on the existing literature data, we discussed the common functioning of dopamine and serotonin neurotransmitters, as well as their contribution to the unique actions in psychophysiological aspect. The dopaminergic and serotoninergic pathways and the receptor classes for dopamine and serotonin were presented, in accordance to the latest literature. Besides their separate action, we discussed their interconnections as well. The interaction of dopaminergic and serotoninergic pathways was presented and the effect of the alteration of one neurotransmitter concentration on another functioning was discussed. The neurodegeneration overview was given as a death of the specific group of neurons and the specific diseases that have connection to dopamine and serotonin transmission disorders were described. Here were also issued the concentration differences of dopamine and serotonin in the periphery and brain, respectively, which result from the brain-blood barrier. The literature data insisted on the more pronounced concentration difference for dopamine, while for serotonin the concentrations in opposite sides of the brain-blood barrier are almost the same. Nevertheless, dopamine concentrations in the opposite sides of the brain-blood barrier correlate with each other. It was concluded that because of the vital importance of both dopamine and serotonin in human organism their concentration should be monitored. The perspectives to predict the possible alterations in neurotransmitter concentrations were discussed.
This article develops an observer-inclusive account of time that reconciles internal (biological, cognitive) and external (physical) temporalities. Its central claim is that low-entropy memory (LEM) is a condition for an agent’s operational access to temporal continuity. By underwriting structured records and the re-identification of states across indices, LEM mediates the agent’s access to succession, duration, and direction. These procedures incur thermodynamic costs. Using Landauer’s principle, we derive a calibrated lower bound on elapsed time for a restricted class of logically irreversible memory updates under isothermal assumptions. The paper proposes a dual-perspectival account of time: objective temporal structure co-varies with the operations of memory-bearing agents who generate and exploit informational repetitions in order to measure and model it, without collapsing external reality into subjectivity. The argument is anchored in canonical results, including Kandel’s and Tonegawa’s work on memory and Prigogine’s theory of dissipative structures.
Neurodegenerative diseases are a global burden that can be fatal, caused by various reasons, including genetic and environmental factors, oxidative stress, aging, disrupted protein folding metabolism, neuroinflammation, and other physical complications. A glial cell, an important part of the brain, is responsible for the stability and functional integrity of neural networks. Recent research has investigated both the positive and negative impacts of glial cells in neurodegenerative diseases, as they have both neuroprotective effects and may also contribute to the neurodegeneration process, especially in the context of neurodegenerative diseases. This study discussed the general pathophysiology and the pathophysiological impact of glial cells in multiple neurodegenerative diseases. We further discussed the impact and mechanisms of glial cells on the development and neuroprotection in various types of neurodegenerative diseases.
Parkinson’s disease (PD) stands as the second most common neurodegenerative disease, characterized by bradykinesia, rigidity, tremors, and loss of dopaminergic neurons in the midbrain. Rotenone is a potential mitochondrial complex‑I inhibitor, involved in PD pathogenesis, while Cryptotanshinone (CT) exhibits neuroprotective activity by its antioxidant and anti-inflammatory properties. This study was framed to investigate the neuroprotective potential of CT against rotenone-induced PD-like symptoms in adult zebrafish. Adult zebrafish (4–5 months) were randomly divided into 6 groups (n = 12), followed by placing them in separate tanks. Rotenone (5 μg/L, water exposure) and CT (10 and 20 mg/kg, i.p.) were administered for 28 days, on the basis of groups. On the 29th day, fish were sacrificed, and their brains and specific brain parts were isolated for further biochemical, neurochemical, histopathological, and immunohistochemical analysis. Results disclosed that rotenone significantly decreased locomotion and triggered anxiety-like behaviour in different mazes, while CT improved them based on the dose. Additionally, CT effectively attenuated the rotenone-induced elevated expression of neuroinflammatory markers, concurrent reduction of cytokine levels, and mitochondrial complex I activity. It also improved various neurotransmitter levels toward normalcy, which were generally imbalanced after rotenone administration. Moreover, the brains collected from rotenone-treated groups revealed neurodegeneration, apoptosis, and morphological alterations, whereas CT preserved neuronal integrity and morphology. Immunohistopathological analysis revealed that CT restored the expression of Nrf2, which was downregulated by rotenone, signifying neuroprotective properties. This research showcased the neuroprotective potential of CT in a dose-dependent manner, offering an alternate therapy in PD management.
In this study, we aimed to assess the effect of sodium fluoride (NaF)-induced toxicity on oxidative stress markers and apoptosis in the brain and serum of mice, and the potential protective effect of quercetin. Forty male Swiss albino mice were divided into Control, NaF (12 mg/kg/day), Q (40 mg/kg/day), and NaF + Q groups and oral gavaged for 30 days. The 8‑OHdG content in the brain tissue was higher in the NaF group than in the control group (p < 0.05). The TOS levels of the serum were significantly higher in every treatment group (p < 0.001), and the serum Aβ-42 levels were significantly higher in the NaF, Q, and NaF + Q groups (p < 0.001) than those in the control group. The serum TAS levels were significantly declined in the NaF group and NaF + Q group (p < 0.01). There was no significant difference among the groups in the brain Aβ-40 and Aβ-42 concentrations. Our results indicate that NaF results in oxidative stress, DNA damage in the brain being one of its triggering effects. Application of quercetin was also observed to attenuate some of these deleterious effects. These findings suggest that quercetin may exert its neuroprotective effect by modulating oxidative stress rather than directly affecting amyloid beta accumulation in brain tissue. Based on such data, quercetin could be a promising candidate for being a protective agent against fluoride-mediated oxidative stress.
Aim: This experimental model assesses the neuroleptic and anti-cognitive potential of a hydroethanolic leaf extract of Colocasia esculenta (HECE) using an in vivo model. Methodology: The study was conducted on Swiss albino mice and comprised two components: cognitive impairment and neuroleptic activity. In the cognitive model, animals were divided into control, negative control, standard, and two treatment groups receiving a hydroethanolic leaf extract of Colocasia esculenta (200 and 400 mg/kg). For neuroleptic assessment, animals were grouped into control (vehicle 10 ml/kg), standard (trihexyphenidyl 10 mg/kg + haloperidol 1 mg/kg), and two test groups receiving the extract (200 and 400 mg/kg) along with haloperidol (1 mg/kg). Behavioural evaluations were performed using the Hebb–William maze, Cook’s pole-climbing test, and haloperidol-induced catalepsy model. Biochemical and histopathological analyses were also conducted. Results: HECE significantly ameliorate cognitive efficacy in the Hebb–William’s maze (p < 0.01), Cook’s pole-climbing test (p < 0.001), and reversing scopolamine-induced model. In both acute and chronic studies (p < 0.001), HECE produced a dose-proportional decline in haloperidol-induced catalepsy. Histopathological findings confirmed reduced neuronal degeneration, with the 400 mg/kg dose exhibiting neuroprotective efficacy comparable to that of standard drugs. All compounds were neurotoxicity-inactive (0.56–0.89), showed minimal GABA receptor interaction, and limited BBB permeability except for quercetin and dimedone; vitexin, luteolin-7-rutinoside, and orientin exhibited moderate clinical toxicity (0.51–0.52), while AChE activity was restricted to luteolin-7-rutinoside and orientin. Conclusion: Hydro-ethanolic leaf extract of Colocasia esculenta (HECE) exhibits neurodegenerative activity and might be useful as a therapy for cognitive dysfunction disease. Furthermore, mechanism of action modulations is described for clinical applicability.
Ischemia-reperfusion (I/R) injury critically impairs neuronal survival, with mitochondrial dysfunction being a central pathogenic factor. Although mild hypothermia has demonstrated neuroprotective potential, the precise mechanisms involving mitochondrial regulation remain incompletely understood. This study investigates whether mild hypothermia protects neurons by preserving mitochondrial membrane potential (MMP) and modulating key mitochondrial apoptosis-related proteins, including caspase‑3, Cytochrome c (Cyt c), Bax, and Bcl‑2. In an in vivo I/R model, nasopharyngeal cavity cooling significantly enhanced neuronal MMP and altered the expression of mitochondrial injury-related proteins. These findings were corroborated in an in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) model, where mild hypothermia also improved MMP and reduced neuronal damage and death. Concurrently, our results indicate that mild hypothermia mitigates neuronal injury by restoring MMP and suppressing the mitochondrial apoptotic pathway. These insights not only elucidate a mechanistic basis for mild hypothermia-induced neuroprotection but also reinforce the therapeutic relevance of mitochondria in I/R injury, supporting the clinical translation of nasopharyngeal cavity cooling for brain protection.
Traumatic brain injury (TBI) and Alzheimer’s disease (AD), are two prominent neurological disorders. Both present a large number of clinical and socio-economic issues, but they are increasingly seen as having common pathways through which they cause disease. For both TBI and AD, oxidative stress and neuro-inflammatory responses lead to neuronal damages, impairment in synaptic function, and continued neuro-degeneration. After TBI, excessive production of oxygen and nitrogen free radicals damages mitochondrial function, while also activating microglial and astroglial cells chronically to cause inflammation. In patients with AD, continued oxidative damage leads to an accumulation of amyloid‑β protein and also leads to an increase in tau phosphorylation. There is an increasing body of literature demonstrating that the pathways by which TBI and AD occur may functionally connect short-term brain injuries to long-term neuro-degenerative processes. This article reviews the available data related to what currently drives the neuronal damage associated with TBI and AD through oxidative stress and inflammation and the available and generating treatment options—particularly antioxidants, anti-inflammatory agents, compounds protecting mitochondria, nanoparticles designed to deliver drugs, and phytochemicals with multi-targeted activity. The focus of this paper is on the scientific data supporting both the mechanistic pathways underlying the damage and the pharmacological/biological therapies that might treat the damage from a single point of view. The innovative aspect of this article lies in its demonstration of the relationship between oxidative stress and inflammation and its impact on the continuum of neuronal disease causing TBI leading to AD, and the potential of multi-targeted therapies to modify the ongoing disease processes.
