J Neuroimmune Pharmacol [JOURNAL]
Sun
200 papers
Vinpocetine and Lactobacillus Attenuated Rotenone-Induced Parkinson's Disease and Restored Dopamine Synthesis in Rats through Modulation of Oxidative Stress, Neuroinflammation, and Lewy Bodies Inclusion.
Hassan HM, Abou-Hany HO, Shata A … +13 more , Hellal D, El-Baz AM, ElSaid ZH, Haleem AA, Morsy NE, Abozied RM, Elbrolosy BM, Negm S, El-Kott AF, AlShehri MA, Khasawneh MA, Saifeldeen ER, Mahfouz MM
J Neuroimmune Pharmacol · 2025 Feb · PMID 39954133 · Publisher ↗
Parkinson's disease (PD) is the main neurodegenerative disorder affecting motor activity, there are different pathophysiological pathways contributing to its development including oxidative stress, neuroinflammation, Lew...
Parkinson's disease (PD) is the main neurodegenerative disorder affecting motor activity, there are different pathophysiological pathways contributing to its development including oxidative stress, neuroinflammation, Lewy's bodies accumulation, and impaired autophagy. Vinpocetine is an herbal extract with antioxidant and anti-inflammatory activities that may counteract pathophysiologic neurodegeneration pathways. Moreover, Lactobacillus is a probiotic that can modulate the gut-brain axis and provide the body with the needed precursors of antioxidants and anti-inflammatory mediators. In the current study PD was induced experimentally in Sprague Dawley rats with rotenone (2.5 mg/kg, i.p, daily) for 60 days, vinpocetine; Vinpo (20 mg/kg, orally, daily) and Lactobacillus; Lacto (2.7 × 10 CFU/ml, orally, daily) were applied as protective treatment. Vinpocetine and Lactobacillus treatment significantly ameliorated motor function by increasing distance traveled and rearing frequency in the open field test with a concomitant increase in falling time from both the accelerating rotarod and the wire screen test. Moreover, vinpocetine and Lactobacillus treatment upregulates tyrosine hydroxylase expression (the rate-limiting enzyme in dopamine synthesis), leading to enhanced dopamine synthesis and improved dopaminergic function with regression of histopathological hallmarks. Antioxidant GSH levels were significantly increased after vinpocetine and Lactobacillus treatment with a significant decrease in MDA content in brain homogenates. Furthermore, vinpocetine and Lactobacillus treatment significantly decreased striatal inflammatory markers; nitrite, IL-1β and TNF-α. Proteinopathies were regressed with a substantial decrease in striatal α-synuclein and tau content. In conclusion, vinpocetine and Lactobacillus treatment reduced rotenone neurotoxicity with improved dopamine release and motor activity with correction of oxidative burden, neuro-inflammation, and proteinopathy.
Pharmacological Depletion of Microglia Protects Against Alcohol-Induced Corticolimbic Neurodegeneration During Intoxication in Male Rats.
Carlson ER, Melbourne JK, Nixon K
J Neuroimmune Pharmacol · 2025 Feb · PMID 39951039 · Full text
Excessive alcohol use damages the brain, especially corticolimbic regions such as the hippocampus and rhinal cortices, leading to learning and memory problems. While neuroimmune reactivity is hypothesized to underly alco...
Excessive alcohol use damages the brain, especially corticolimbic regions such as the hippocampus and rhinal cortices, leading to learning and memory problems. While neuroimmune reactivity is hypothesized to underly alcohol-induced damage, direct evidence of the causal role of microglia, brain-resident immune cells, in this process is lacking. Here, we depleted microglia using PLX5622 (PLX), a CSF1R inhibitor commonly used in mice, but rarely in rats, and assessed cell death following binge-like alcohol exposure in male rats. Eleven days of PLX treatment depleted microglia > 90%. Further, PLX treatment prevented alcohol-induced neuronal death in the hippocampus and rhinal cortices, as the number of FluoroJade-B-positive cells (dying neurons) was reduced to control diet levels. This study provides direct evidence that alcohol-induced microglial reactivity is neurotoxic in male rats. Improved understanding of alcohol-microglia interactions is essential for developing therapeutics that suppress pro-cytotoxic and/or amplify protective microglia activity to relieve alcohol-related damage.
GDF11 Mitigates Neuropathic Pain via Regulation of Microglial Polarization and Neuroinflammation through TGF-βR1/SMAD2/NF-κB Pathway in Male Mice.
Liu T, Zhang L
J Neuroimmune Pharmacol · 2025 Feb · PMID 39939465 · Publisher ↗
Spinal microglial activation and the polarization towards the M1 phenotype are implicated in the pathological process of neuropathic pain. Extensive research has elucidated that growth and differentiation factor 11 (GDF1...
Spinal microglial activation and the polarization towards the M1 phenotype are implicated in the pathological process of neuropathic pain. Extensive research has elucidated that growth and differentiation factor 11 (GDF11), a constituent of the transforming growth factor-β (TGF-β) superfamily, exerts inhibitory effects on macrophage activation and mitigates inflammatory responses via the activation of TGF-β receptor type I (TGF-βR1). Nonetheless, the influence of GDF11 on spinal microglial polarization and its role in neuropathic pain remains to be ascertained. In the present investigation, a neuropathic pain model was induced via a spared nerve injury (SNI) procedure on the sciatic nerve in male mice. The impact of GDF11 on microglial polarization and neuropathic pain in SNI-subjected mice was evaluated through pain behavior assessments, WB, IF, qRT-PCR, and ELISA. Our findings revealed a significant downregulation of spinal GDF11 and TGF-βR1 expression levels in microglia of mice subjected to SNI. Furthermore, GDF11 treatment notably reversed the mechanical allodynia and thermal hyperalgesia, inhibited M1 microglial polarization, and attenuated neuroinflammatory processes by modulating the SMAD2/NF-κB in SNI mice. However, the analgesic effects of GDF11 on pain hypersensitivity and its modulatory influence on spinal microglial polarization were abrogated by the application of a specific antagonist of TGF-βR1, or the TGF-βR1 siRNA. In summary, GDF11 effectively ameliorated mechanical allodynia and thermal hyperalgesia, suppressed M1 microglial polarization, and alleviated neuroinflammation via the regulation of the TGF-βR1/SMAD2/NF-κB pathway in mice with SNI. These findings suggest that GDF11 holds promise as a therapeutic modality for the management of neuropathic pain.
Loganic Acid Alleviates the Olfactory-Brain NLRP3 Inflammasome Activation and Rescues Dopaminergic Neurons in Experimental Models of Parkinson's Disease.
Panda SR, Panja P, Singh M … +7 more , Soni U, Rajdev B, Garg P, Pawar SD, Acharya R, Ranade A, Naidu VGM
J Neuroimmune Pharmacol · 2025 Feb · PMID 39934492 · Publisher ↗
The NLRP3 inflammasome signaling cascade activation is a significant contributor to the initiation and progression of Parkinson's disease (PD). Recent evidence supports that targeting NLRP3 inflammasome assembly could be...
The NLRP3 inflammasome signaling cascade activation is a significant contributor to the initiation and progression of Parkinson's disease (PD). Recent evidence supports that targeting NLRP3 inflammasome assembly could be a potential strategy to halt PD progression. The molecular mechanism of the olfactory-brain axis in mediating PD remains elusive. The current study explores that MPTP exposure to C57BL/6 mice leads to glial cell activation and impairs the olfactory function. The role of NLRP3 inflammasome activation in the olfactory bulb and the brain mediating neuroinflammation and neurodegeneration by activating multiple inflammatory pathways is explored. Loganic acid (LA), an iridoid glycoside, has been shown to provide antioxidant, anti-inflammatory, and inhibit microglial activation. Our results in-vitro studies demonstrated that LA treatment in MPP-induced microglial cells inhibits NLRP3 inflammasome assembly, halts phagocytosis, and downregulates the release of pro-inflammatory cytokines such as IL-1β and IL-18. Further, results confirm that LA increases the neuronal differentiation markers and assists neurite growth. To correlate the in-vitro experiments with the in-vivo study, LA treatment prevented the loss of olfactory and motor function. In immunoblotting, LA treatment significantly inhibits the expression of NLRP3 inflammasome signaling cascade when compared to the MPTP group of the olfactory bulb and substantia nigra. Computational studies on LA on IL-β, NLRP3, caspase-1, and ASC also support strong evidence in the downregulation of inflammasome and cytokines through potential non-covalent interactions. The results confirm the neuroprotective effect of LA in PD by halting the NLRP3 inflammasome activation in the olfactory bulb and nigra region of the mice.
Reduction of Neuroinflammation as a Common Mechanism of Action of Anorexigenic and Orexigenic Peptide Analogues in the Triple Transgenic Mouse Model of Alzheimer´s Disease.
Mengr A, Šmotková Z, Pačesová A … +3 more , Železná B, Kuneš J, Maletínská L
J Neuroimmune Pharmacol · 2025 Feb · PMID 39932627 · Full text
Alzheimer's disease (AD) is the most common form of dementia. Characterized by progressive neurodegeneration, AD typically begins with mild cognitive decline escalating to severe impairment in communication and responsiv...
Alzheimer's disease (AD) is the most common form of dementia. Characterized by progressive neurodegeneration, AD typically begins with mild cognitive decline escalating to severe impairment in communication and responsiveness. It primarily affects cerebral regions responsible for cognition, memory, and language processing, significantly impeding the functional independence of patients. With nearly 50 million dementia cases worldwide, a number expected to triple by 2050, the need for effective treatments is more urgent than ever. Recent insights into the association between obesity, type 2 diabetes mellitus, and neurodegenerative disorders have led to the development of promising treatments involving antidiabetic and anti-obesity agents. One such novel promising candidate for addressing AD pathology is a lipidized analogue of anorexigenic peptide called prolactin-releasing peptide (palm-PrRP31). Interestingly, anorexigenic and orexigenic peptides have opposite effects on food intake regulation, however, both types exhibit neuroprotective properties. Recent studies have also identified ghrelin, an orexigenic peptide, as a potential neuroprotective agent. Hence, we employed both anorexigenic and orexigenic compounds to investigate the common mechanisms underpinning their neuroprotective effects in a triple transgenic mouse model of AD (3xTg-AD mouse model) combining amyloid-beta (Aβ) pathology and Tau pathology, two hallmarks of AD. We treated 3xTg-AD mice for 4 months with two stable lipidized anorexigenic peptide analogues - palm-PrRP31, and liraglutide, a glucagon-like peptide 1 (GLP-1) analogue - as well as Dpr-ghrelin, a stable analogue of the orexigenic peptide ghrelin, and using the method of immunohistochemistry and western blot demonstrate the effects of these compounds on the development of AD-like pathology in the brain. Palm-PrRP31, Dpr-ghrelin, and liraglutide reduced intraneuronal deposits of Aβ plaque load in the hippocampi and amygdalae of 3xTg-AD mice. Palm-PrRP31 and Dpr-ghrelin reduced microgliosis in the hippocampi, amygdalae, and cortices of 3xTg-AD mice. Palm-PrRP31 and liraglutide reduced astrocytosis in the amygdalae of 3xTg-AD mice. We propose that these peptides are involved in reducing inflammation, a common mechanism underlying their therapeutic effects. This is the first study to demonstrate improvements in AD pathology following the administration of both orexigenic and anorexigenic compounds, highlighting the therapeutic potential of food intake-regulating peptides in neurodegenerative disorders.
Treg Upregulation by Treadmill Training Accelerates Myelin Repair Post-Ischemia.
Zhong J, Liu T, He Y … +8 more , Zhu Y, Li S, Liu Y, Yang C, Yu L, Pan L, Yin Y, Tan B
J Neuroimmune Pharmacol · 2025 Feb · PMID 39930306 · Publisher ↗
Regulatory T (Treg) cells contribute to white matter repair following ischemic stroke, but their limited availability in circulation restricts their therapeutic potential. Exercise, as a non-invasive and effective rehabi...
Regulatory T (Treg) cells contribute to white matter repair following ischemic stroke, but their limited availability in circulation restricts their therapeutic potential. Exercise, as a non-invasive and effective rehabilitation method, has been shown to restore Treg balance in diseases. This study explores the effects of treadmill training on Treg upregulation and its influence on myelin repair and functional recovery in rats with middle cerebral artery occlusion (MCAO). After four weeks of treadmill training, we analyzed the proportion of Treg cells (Tregs), FOXP3 expression, and oligodendrocyte-related protein levels using flow cytometry, immunofluorescence, and Western blotting. Myelin structure was examined with transmission electron microscopy (TEM), while motor coordination and balance were assessed using the fatigue rotarod and CatWalk analysis systems. To further explore the role of Tregs, the FOXP3 inhibitor P60 was used to inhibit Treg activity. The findings of our study indicate that training on a treadmill supports the maturation of oligodendrocytes, leads to an increase in myelin-associated proteins and the thickness of myelin, and promotes the recovery of motor function. Inhibition of Treg activity diminished these benefits, highlighting Tregs' key role in exercise-induced remyelination. These findings suggest that treadmill training facilitates myelin regeneration and functional recovery by upregulating Tregs, offering potential new strategies for stroke treatment.
Proteomic Analysis of Chronic Binge Alcohol-Induced Hippocampal and Anterior Cingulate Cortex Neuroadaptations in Simian Immunodeficiency Virus (SIV)-Infected Female Rhesus Macaques.
Fitzpatrick-Schmidt T, Mansouri A, Adamec J … +7 more , Klein J, Coleman L, Edwards KN, Simon L, Molina PE, Salling MC, Edwards S
J Neuroimmune Pharmacol · 2025 Feb · PMID 39930298 · Full text
Human immunodeficiency virus (HIV) infection produces neurological comorbidities including HIV-associated neurocognitive disorder (HAND) and chronic pain. HIV also increases the risk of developing an alcohol use disorder...
Human immunodeficiency virus (HIV) infection produces neurological comorbidities including HIV-associated neurocognitive disorder (HAND) and chronic pain. HIV also increases the risk of developing an alcohol use disorder (AUD). With the rising prevalence of AUD in women and people with HIV (PWH), understanding the neurobiological impact of alcohol in these populations is important. We examined proteomic alterations in the hippocampus and anterior cingulate cortex (ACC), brain regions critical for cognition and affective pain, in a female rhesus macaque model of chronic binge alcohol administration and SIV infection. Adult female rhesus macaques received either chronic binge alcohol (CBA, 13-14 g/kg/week of alcohol) or water (VEH) via gastric catheter. All animals were inoculated with simian immunodeficiency virus (SIV) and treated with antiretroviral therapy (ART). Brain samples were processed for proteomic analysis, and quantitative discovery-based proteomics identified differentially expressed proteins in both brain regions comparing CBA treatment to VEH. Ingenuity Pathway Analysis (IPA) was also used to predict pathway activation. CBA significantly altered 147 proteins in the hippocampus and 176 proteins in the ACC. IPA revealed alterations in 39 canonical pathways in the hippocampus and 62 canonical pathways in the ACC. Fourteen common canonical pathways were enriched in both regions, including synaptogenesis and protein kinase A (PKA) signaling. These discoveries expand our understanding of how alcohol alters proteins of critical signaling pathways in vulnerable brain regions in the context of SIV/HIV infection and may lead to the development of new pharmacological treatment avenues for neurological dysfunction in women with HIV who use alcohol.
Rebalancing Immune Interactions within the Brain-Spleen Axis Mitigates Neuroinflammation in an Aging Mouse Model of Alzheimer's Disease.
Cantone AF, Burgaletto C, Di Benedetto G … +7 more , Gaudio G, Giallongo C, Caltabiano R, Broggi G, Bellanca CM, Cantarella G, Bernardini R
J Neuroimmune Pharmacol · 2025 Feb · PMID 39918606 · Full text
Alzheimer's disease (AD) is the most common cause of dementia worldwide, characterized by accumulation of amyloid-β protein and hyperphosphorylated tau protein in the brain. Neuroinflammation, resulting from chronic acti...
Alzheimer's disease (AD) is the most common cause of dementia worldwide, characterized by accumulation of amyloid-β protein and hyperphosphorylated tau protein in the brain. Neuroinflammation, resulting from chronic activation of brain-resident innate immune cells as well as enhanced peripheral leukocyte access across the blood-brain barrier, crucially affects AD progression. In this context, TNFSF10, a cytokine substantially expressed in the AD brain, has been shown to modulate both the innate and the adaptive branches of the immune response in AD-related neuroinflammation. In this study, we explored whether a TNFSF10-neutralizing treatment could represent a tool to re-balance the overall overshooting inflammatory response in a mouse model of AD. Specifically, 3xTg-AD mice were treated sub-chronically with an anti-TNFSF10 monoclonal antibody for three months, and were then sacrificed at 15 months. TNFSF10 neutralization reduced the expression of the inflammatory marker CD86, inversely related to levels of the anti-inflammatory marker CD206 in the brain of 3xTg-AD mice, suggesting a switch of microglia towards a neuroprotective phenotype. Similar results were observed in the splenic macrophage population. Moreover, flow cytometry revealed a significant decrease of CD4CD25FOXP3 T regulatory cells as well as reduced number of CD11bLY6C proinflammatory monocytes in both the brain and the spleen of 3xTg-AD mice treated with anti-TNFSF10 monoclonal antibody. Finally, the treatment resulted in lower count of splenic CD4 and CD8 T cells expressing PD1. The data suggest that TNFSF10 system-targeted treatment effectively restrain overshooting central and peripheral inflammation by rebalancing the overall immune response, mitigating the progression of AD pathology.
A New Perspective on Mechanisms of Neurodegeneration in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis: the Early and Critical Role of Platelets in Neuro/Axonal Loss.
Orian JM
J Neuroimmune Pharmacol · 2025 Feb · PMID 39904925 · Full text
Multiple sclerosis (MS) is a central nervous system (CNS) autoimmune disorder, with limited treatment options. This disease is characterized by differential pathophysiology between grey matter (GM) and white matter (WM)....
Multiple sclerosis (MS) is a central nervous system (CNS) autoimmune disorder, with limited treatment options. This disease is characterized by differential pathophysiology between grey matter (GM) and white matter (WM). The predominant WM hallmark is the perivascular plaque, associated with blood brain barrier (BBB) loss of function, lymphocytic infiltration, microglial reactivity, demyelination and axonal injury and is adequately addressed with immunomodulatory drugs. By contrast, mechanisms underlying GM damage remain obscure, with consequences for neuroprotective strategies. Cortical GM pathology is already significant in early MS and characterized by reduced BBB disruption and lymphocytic infiltration relative to WM, but a highly inflammatory environment, microglial reactivity, demyelination and neuro/axonal loss. There is no satisfactory explanation for the occurrence of neurodegeneration without large-scale inflammatory cell influx in cortical GM. A candidate mechanism suggests that it results from soluble factors originating from meningeal inflammatory cell aggregates, which diffuse into the underlying cortical tissue and trigger microglial activation. However, the recent literature highlights the central role of platelets in inflammation, together with the relationship between coagulation factors, particularly fibrinogen, and tissue damage in MS. Using the experimental autoimmune encephalomyelitis (EAE) model, we identified platelets as drivers of neuroinflammation and platelet-neuron associations from the pre-symptomatic stage. We propose that fibrinogen leakage across the BBB is a signal for platelet infiltration and that platelets represent a major and early participant in neurodegeneration. This concept is compatible with the new appreciation of platelets as immune cells and of neuronal damage driven by inflammatory cells sequestered in the meninges.
PKR Inhibition Prevents Neuroinflammation and Rescues Depressive-Like Behaviors via BDNF/TrkB Signaling.
Hu Y, Ali T, Mou S … +6 more , Gong Q, Gao R, Luo Y, Li S, Ling L, Hao L
J Neuroimmune Pharmacol · 2025 Feb · PMID 39903347 · Publisher ↗
PKR, a kinase implicated in inflammation, accumulates in the brain, but its role in neuroinflammation-related depression is poorly understood. This study aimed to investigate whether pharmacological PKR inhibition using...
PKR, a kinase implicated in inflammation, accumulates in the brain, but its role in neuroinflammation-related depression is poorly understood. This study aimed to investigate whether pharmacological PKR inhibition using C16 (PKR inhibitor) could reverse LPS-induced neuroinflammation and depressive-like behaviors. Mice (C57BL/6J, 20-22 g, 6-8 weeks old) were administered LPS intraperitoneally for three days to induce depressive-like behavior and neuroinflammation. Simultaneously, mice were treated with C16 (a pharmacological PKR inhibitor) intraperitoneally for the same duration, followed by behavioral assessments. After euthanasia, brain-hippocampus tissues were collected for biochemical analysis. To validate these in vivo findings, BV2 and HT22 cells were cultured and subjected to pharmacological and biochemical analysis. LPS treatment significantly increased hippocampal neuroinflammation (GFAP/IBA-1 p < 0.001), cytokine production (IL-1β, IL-6, TNF-α, p < 0.05), PKR phosphorylation (p < 0.05), and inflammatory signaling (NLRP3/ASC, p < 0.001). Concomitantly, LPS exposure induced depressive-like symptoms (p < 0.001), impaired synaptic function (Synasin-1/SNAP25, p < 0.05), spine numbers (p < 0.001), and downregulated brain-derived neurotrophic factor (BDNF) /TrkB signaling (p < 0.001). Importantly, these effects were attenuated by C16, a PKR inhibitor. C16 also reduced LPS-induced ER stress markers in the hippocampus (p < 0.05). Interestingly, K252a, a BDNF/TrkB inhibitor, reversed the protective effects of C16, increasing both neuroinflammation (p < 0.001) and depressive symptoms (p < 0.001) in LPS-treated mice. Notably, in vitro studies using BV2 and HT22 cells corroborated these findings. In conclusion, these findings suggest that PKR is critical in mediating LPS-induced neuroinflammation and depressive-like behaviors, potentially through interactions with BDNF/TrkB signaling.
The Effects of Cannabinoids on Ischemic Stroke-Associated Neuroinflammation: A Systematic Review.
Alraddadi EA, Aljuhani FF, Alsamiri GY … +4 more , Hafez SY, Alselami G, Almarghalani DA, Alamri FF
J Neuroimmune Pharmacol · 2025 Feb · PMID 39899062 · Full text
Stroke represents a significant burden on global health and the economy, with high mortality rates, disability, and recurrence. Ischemic stroke is a serious condition that occurs when a blood vessel in the brain is inter...
Stroke represents a significant burden on global health and the economy, with high mortality rates, disability, and recurrence. Ischemic stroke is a serious condition that occurs when a blood vessel in the brain is interrupted, reducing the blood supply to the affected area. Inflammation is a significant component in stroke pathophysiology. Neuroinflammation is triggered following the acute ischemic ictus, where the blood-brain barrier (BBB) breaks down, causing damage to the endothelial cells. The damage will eventually generate oxidative stress, activate the pathological phenotypes of astrocytes and microglia, and lead to neuronal death in the neurovascular unit. As a result, the brain unleashes a robust neuroinflammatory response, which can further worsen the neurological outcomes. Neuroinflammation is a complex pathological process involved in ischemic damage and repair. Finding new neuroinflammation molecular targets is essential to develop effective and safe novel treatment approaches against ischemic stroke. Accumulating studies have investigated the pharmacological properties of cannabinoids (CBs) for many years, and recent research has shown their potential therapeutic use in treating ischemic stroke in rodent models. These findings revealed promising impacts of CBs in reducing neuroinflammation and cellular death and ameliorating neurological deficits. In this review, we explore the possibility of the therapeutic administration of CBs in mitigating neuroinflammation caused by a stroke. We summarize the results from several preclinical studies evaluating the efficacy of CBs anti-inflammatory interventions in ischemic stroke. Although convincing preclinical evidence implies that CBs targeting neuroinflammation are promising for ischemic stroke, translating these findings into the clinical setting has proven to be challenging. The translation hurdle is due to the essence of the CBs ability to cause anxiety, cognitive deficit, and psychosis. Future studies are warranted to address the dose-beneficial effect of CBs in clinical trials of ischemic stroke-related neuroinflammation treatment.
A Comparative Study of Nanoconjugates of a Synthetic and a Natural Drug Against T2DM-Induced Cognitive Dysfunction.
Pradhan SP, Behera A, Sahu PK
J Neuroimmune Pharmacol · 2025 Feb · PMID 39893302 · Publisher ↗
Type II Diabetes Mellitus (T2DM) is one of the risk factors for the development of dementia leading to cognitive dysfunctions. The present study evaluates the efficacy of a synthetic drug (Vildagliptin, VLD) and a natura...
Type II Diabetes Mellitus (T2DM) is one of the risk factors for the development of dementia leading to cognitive dysfunctions. The present study evaluates the efficacy of a synthetic drug (Vildagliptin, VLD) and a natural glycosidic compound (Hesperidin, HSP) against T2DM-induced cognitive dysfunction in rats. The drugs were conjugated with metal nanoparticles like gold (Au) and selenium (Se) to enhance their efficacy. The synthesis of the monometallic and bimetallic nanoparticles of VLD and HSP was established via the turkevich method and characterised by different spectroscopical techniques like UV (Ultraviolet)-visible, FTIR (Fourier Transform Infrared Spectroscopy), zeta potential, particle size, HR-TEM (High Resolution Transmission Electron Microscopy), SAED (Selected Area Electron Diffraction) and SEM-EDX (Scanning Electron Microscopy with Energy Dispersive X-ray Analysis). Both Streptozotocin (STZ) of 65 mg/kg (Group I-X) and Alloxan (ALX) of 150 mg/kg (Group I-X) were injected into 120 Wistar rats to induce cognitive dysfunction. After the induction, the BGL levels were evaluated and rats with BGL > 250 mg/dl were used in the study. Then the test drug and nanoformulations were administered for 21 days. Neurobehavioral assessment, antioxidant studies, and estimation of AChE (acetylcholinesterase) and nitrite levels were done. The VLD and HSP with its nanoconjugates significantly attenuated the effect of STZ and ALX by improving the memory and learning function in Y-maze, radial arm maze (RAM), and elevated plus maze (EPM), increased antioxidant levels of SOD (superoxide dismutase), CAT (catalase), and GSH (glutathione); decreased lipid peroxidation and reduced the AChE and nitrite levels in the rat brain. The bimetallic nanoconjugates of both VLD and HSP were more effective than the monometallic forms of VLD and HSP. However, VLD and its nanoconjugates exhibited better neuroprotective activity than HSP and its nanoconjugates in STZ and ALX animal models. VLD and its nanoformulations were more effective against long-term memory than HSP and its nanoconjugates. Both VLD and HSP may be a potential lead for cognitive and neurodegenerative diseases.
NXP032 Improves Memory Impairment Through Suppression of Tauopathy in PS19 Mice and Attenuates Okadaic Acid-Induced Tauopathy in SH-SY5Y Cells.
Eo H, Kim SH, Ju IG … +3 more , Lee JH, Oh MS, Kim YJ
J Neuroimmune Pharmacol · 2025 Feb · PMID 39891801 · Publisher ↗
Tauopathy is widely observed in multiple neurodegenerative diseases such as Alzheimer's disease (AD) and characterized by abnormal tau protein phosphorylation, aggregation and its accumulation as a form of neurofibrillar...
Tauopathy is widely observed in multiple neurodegenerative diseases such as Alzheimer's disease (AD) and characterized by abnormal tau protein phosphorylation, aggregation and its accumulation as a form of neurofibrillary tangle (NFT) in the brain. However, there are no effective treatments targeting tau pathology in the AD. Vitamin C is known to reduce tauopathy and modulate one of its regulators called glycogen synthase kinase 3 (GSK3) in the body. Nevertheless, vitamin C has a limitation of its stability during metabolism due to its chemical properties. Thus, in the current study, NXP032 (a vitamin C/aptamer complex) was tested as a candidate for tau-targeting treatment because it can preserve antioxidative efficacy of vitamin C before it can reach the target tissue. In this context, the current study aimed to investigate the therapeutic effect of NXP032 on tauopathy in vivo and in vitro. As a result, NXP032 attenuated cognitive and memory decline and reduced NFT and tau hyperphosphorylation in the P301S mutant human tau transgenic mice (or called PS19 mice). In addition, NXP032 suppressed neuroinflammation found in the PS19 mice. Furthermore, NXP032 protected SH-SY5Y human neuroblastoma cells from okadaic acid (OKA)-induced cytotoxicity. Especially, 10 ng/ml of NXP032 reduced tau hyperphosphorylation and GSK3 activation though its phosphorylation at Tyr216 site which were promoted by OKA treatment in the SH-SY5Y cells. Taken together, our results suggest that NXP032 might be a potential therapy for AD and tauopathy-related neurodegenerative disorders as well.
Modulation of Intestinal Inflammation and Protection of Dopaminergic Neurons in Parkinson's Disease Mice through a Probiotic Formulation Targeting NLRP3 Inflammasome.
Zhou L, Wong KY, Xie H
J Neuroimmune Pharmacol · 2025 Jan · PMID 39826038 · Full text
Emerging evidence highlights the significance of peripheral inflammation in the pathogenesis of Parkinson's disease (PD) and suggests the gut as a viable therapeutic target. This study aimed to explore the neuroprotectiv...
Emerging evidence highlights the significance of peripheral inflammation in the pathogenesis of Parkinson's disease (PD) and suggests the gut as a viable therapeutic target. This study aimed to explore the neuroprotective effects of the probiotic formulation VSL#3 and its underlying mechanism in a PD mouse model induced by MPTP. Following MPTP administration, the striatal levels of dopamine and its metabolites, as along with the survival rate of dopaminergic neurons in the substantia nigra, were significantly reduced in PD mice. MPTP also significantly increased the mRNA expression of pro-inflammatory cytokines TNF-α and IL-1β, while reducing anti-inflammation mediators, like glia cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) in the striatum. These pathological changes were notably mitigated by VSL#3 treatment, suggesting its neuroprotective and anti-inflammatory effects in the brain. Additionally, VSL#3 significantly lowered the circulating levels of pro-inflammatory cytokines, and reduced TNF-α and IL-1β mRNA expression in the liver, indicating an inhibition of cytokine transfer. In the intestine, the probiotic treatment markedly decreased the mRNA expression of pro-inflammatory cytokines, (TNF-α, IL-1β, IL-6 and IL-17), and the other two key components of the NLRP3 inflammasome, caspase-1 and NLRP3, demonstrating an inhibition of VSL#3 on gut NLRP3 inflammasome. VSL#3 exerts neuroprotective effects in PD mice through the suppression of intestinal inflammation, particularly inhibiting the intestinal NLRP3 inflammasome. This study supports the therapeutic potential of targeting intestinal inflammation and utilizing probiotics in PD treatment.
The High-Affinity IL-2 Receptor Affects White Matter Damage after Cerebral Ischemia by Regulating CD8 + T Lymphocyte Differentiation.
Li Y, Jiang Q, Geng X … +1 more , Zhao H
J Neuroimmune Pharmacol · 2025 Jan · PMID 39821696 · Publisher ↗
IL-2/IL-2R inhibition improved the prognosis of ischemic stroke by regulating T cells, while the respective contribution of T cells with high/medium/low-affinity IL-2 receptors remained unclear. Single-cell RNA sequencin...
IL-2/IL-2R inhibition improved the prognosis of ischemic stroke by regulating T cells, while the respective contribution of T cells with high/medium/low-affinity IL-2 receptors remained unclear. Single-cell RNA sequencing data of ischemic brain tissue revealed that most of the high-affinity IL-2R would be expressed by CD8 + T cells, especially by a highly-proliferative subset. Interestingly, only the CD8 + T cells with high-affinity IL-2R infiltrated ischemic brain tissues, highly expressing 32 genes (including Cdc20, Cdca3/5, and Asns) and activating 7 signaling pathways (including the interferon-alpha response pathway, a key mediator in the proliferation, migration, and cytotoxicity of CD8 + T cells). Its interaction with endothelial cells and the ligand-receptor interaction analysis also suggested an augmented brain infiltration after cerebral ischemia. In IL-2Rα KO mice, who would have no high- or low-affinity IL-2R in CD8 + T cells, the RNA-seq, qPCR, immunofluorescence, and multiplex assays found that the expression of CD8b, CD122, CD132, and Vcam-1 was upregulated in the acute phase of cerebral ischemia, with decreasing H2-k1 positive cells and increasing Vcam-1 and CD8b positive cells in brain tissue. However, inflammation pathways in brain were inhibited and peripheral inflammatory cytokine levels were reduced, indicating that CD8 + T cells changed into an anti-inflammatory phenotype. The IL-2Rα KO mice after cerebral ischemia also performed better in behavioral tests and had more favorable results in diffusion tensor imaging, electrophysiology, and MBP testing. Our findings suggested that the CD8 + T cells with high-affinity IL-2R, as well as IL-2Rα, might be targeted to improve the clinical management of ischemic stroke.
LncRNA NEAT1, an Important Biomarker Involved in the Pathological and Physiological Processes of Parkinson's Disease.
Chen R, Zhang Y, Shen Y … +3 more , Wu K, Mo X, Yang Z
J Neuroimmune Pharmacol · 2025 Jan · PMID 39808217 · Publisher ↗
Parkinson's disease (PD) is a complex progressive neurodegenerative disorder and the pathogenesis and treatment methods are unknown. This aim is to investigate the effects of long non coding RNA NEAT1 (LncRNA NEAT1) on 1...
Parkinson's disease (PD) is a complex progressive neurodegenerative disorder and the pathogenesis and treatment methods are unknown. This aim is to investigate the effects of long non coding RNA NEAT1 (LncRNA NEAT1) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD). Immunoprecipitation and western blot were used to search for the effects of LncRNA NEAT1 on PD. Tyrosine hydroxylase (TH) and brain derived neurotrophic factor (BDNF) were evaluated in substantia nigra (SN) region of the brain by immunohistochemical staining. Compared with the control group, the relative expression level of LncRNA NEAT1 in the MPTP group was significantly increased. LncRNA NEAT1 is negatively correlated with miR-376b-3p. LncRNA NEAT1 significantly increased oxidative stress, neuroinflammation along with enhanced neurotrophic potential via NLR family Pyrin domain protein 3 (NLRP3) pathway. In conclusion, these results indicated that LncRNA NEAT1 participated in the pathophysiological of PD and its mechanism via the miR-376b-3p/NLRP3 signaling pathway.
Ghrelin Induces Ferroptosis Resistance and M2 Polarization of Microglia to Alleviate Neuroinflammation and Cognitive Impairment in Alzheimer's Disease.
Guo Y, Zhao J, Liu X … +5 more , Lu P, Liang F, Wang X, Wu J, Hai Y
J Neuroimmune Pharmacol · 2025 Jan · PMID 39797928 · Publisher ↗
Microglial polarization and ferroptosis are important pathological features in Alzheimer's disease (AD). Ghrelin, a brain-gut hormone, has potential neuroprotective effects in AD. This study aimed to explore the potentia...
Microglial polarization and ferroptosis are important pathological features in Alzheimer's disease (AD). Ghrelin, a brain-gut hormone, has potential neuroprotective effects in AD. This study aimed to explore the potential mechanisms by which ghrelin regulates the progression of AD, as well as the crosstalk between microglial polarization and ferroptosis. Mouse BV2 microglial cells and male mice were treated with beta-amyloid (Aβ) (1-42) to simulate the AD environment. Microglia ferroptosis was measured by detecting levels of ferroptosis-related proteins (SLC7A11, GPX4, FTL1, and FTH1), metabolic markers (ROS, MDA, GSH, SOD), and observing mitochondrial morphological changes. Microglial polarization was evaluated by measuring levels of inflammatory markers and surface markers. The impact of ghrelin on Aβ-exposed microglia was assessed by coupling with the ferroptosis activator Erastin. Cognitive impairment in AD mice was evaluated through behavioral tests. Tissue staining was applied to determine neuronal damage. In Aβ-exposed microglia, ghrelin upregulated the protein expression of SLC7A11, GPX4, FTL1 and FTH1, reduced ROS and MDA levels, and elevated GSH and SOD levels through the BMP6/SMAD1 pathway. Ghrelin alleviated mitochondrial structural damage. Additionally, ghrelin reduced levels of pro-inflammatory factors and CD86, while increasing levels of anti-inflammatory factors and CD206. Erastin reversed the effects of ghrelin on ferroptosis and phenotypic polarization in Aβ-exposed microglia. In AD mice, ghrelin ameliorated abnormal behavior, neuroinflammation, and plaque deposition. Ghrelin attenuated iNOS/IBA1-positive expression and enhanced Arg-1/IBA1-positive expression in the hippocampus. Ghrelin induces microglial M2 polarization by inhibiting microglia ferroptosis, thereby alleviating neuroinflammation. Our results indicate that ghrelin may serve as a promising potential agent for treating cognitive impairment in AD.
Empagliflozin Mitigates PTZ-Induced Seizures in Rats: Modulating Npas4 and CREB-BDNF Signaling Pathway.
Abdelaziz HA, Hamed MF, Ghoniem HA … +2 more , Nader MA, Suddek GM
J Neuroimmune Pharmacol · 2025 Jan · PMID 39776284 · Full text
Empagliflozin (EMPA) is one of the sodium/glucose cotransporter 2 (SGLT2) inhibitors that has been recently approved for the treatment of diabetes mellitus type II. Recently, EMPA has shown protective effects in differen...
Empagliflozin (EMPA) is one of the sodium/glucose cotransporter 2 (SGLT2) inhibitors that has been recently approved for the treatment of diabetes mellitus type II. Recently, EMPA has shown protective effects in different neurological disorders, besides its antidiabetic activity. Kindling is a relevant model to study epilepsy and neuroplasticity. This study aimed to investigate the potential protective effects of EMPA (1 and 3 mg/kg orally) against convulsant effects induced by pentylenetetrazole (PTZ) using a modified window- (win-) PTZ kindling protocol. The biochemical dysfunction and hippocampal damage induced by PTZ were profoundly reversed by EMPA treatment in a dose-dependent manner, as evidenced by the significant increase in reduced glutathione (GSH) and decrease in malondialdehyde (MDA) hippocampal contents. Furthermore, EMPA counteracted PTZ-induced neuronal damage in the hippocampal region, as confirmed by histopathological examination of the hippocampal tissues. EMPA impaired astrocytosis and showed an antiapoptotic effect through a significant reduction of glial fibrillary acidic protein (GFAP) and BCL2-Associated X Protein (BAX) expressions, respectively. Interestingly, EMPA exhibited an antiepileptic effect against PTZ-induced seizures through significantly reducing neuronal PAS domain Protein 4 (Npas4), cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) hippocampal expressions, and enhancing the brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) pathway, which are found to be involved in epileptogenesis, eventually leading to significant improvement of behavioral impairments induced by PTZ. Hence, these results showed further prospective insights for EMPA as a neuroprotective agent.
Memantine/Rosuvastatin Therapy Abrogates Cognitive and Hippocampal Injury in an Experimental Model of Alzheimer's Disease in Rats: Role of TGF-β1/Smad Signaling Pathway and Amyloid-β Clearance.
Zidan EF, El-Mezayen NS, Elrewini SH … +2 more , Afify EA, Ali MA
J Neuroimmune Pharmacol · 2024 Dec · PMID 39708240 · Full text
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder of complex pathogenesis and multiple interacting signaling pathways where amyloidal-β protein (Aβ) clearance plays a crucial role in cognitive decli...
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder of complex pathogenesis and multiple interacting signaling pathways where amyloidal-β protein (Aβ) clearance plays a crucial role in cognitive decline. Herein, the current study investigated the possible modulatory effects of memantine/ rosuvastatin therapy on TGF-β1/p-Smad/p21 signaling pathway and their correlation to the blood brain barrier transporters involved in Aβ-clearance and microRNAs as a novel molecular mechanism in AD treatment. AD was induced by a single intracerebroventricular streptozotocin injection (ICV-STZ, 3 mg/kg) in rats and drug therapy was continued for 28 days after AD induction. Efficacy was monitored by applying a battery of behavioral assessments, as well as biochemical, histopathological, molecular and gene expression techniques. The upregulated TGF-β1-signaling in the untreated rats was found to be highly correlated to transporters and microRNAs governing Aβ-efflux; ABCA1/miRNA-26 and LRP1/miRNA-205 expressions, rather than RAGE/miRNA-185 controlling Aβ-influx; an effect that was opposed by the tested drugs and was found to be correlated with the abolished TGF-β1-signaling as well. Combined memantine/rosuvastatin therapy ameliorated the STZ evoked decreases in escape latency and number of crossovers in the Morris water maze test, % spontaneous alternation in the Y-maze test, and discrimination and recognition indices in the object recognition test. The evoked behavioral responses were directly related to the β-amyloid accumulation and the alteration in its clearance. Additionally, drug treatment increased brain glutathione and decreased malondialdehyde levels. These findings were histopathologically confirmed by a marked reduction of gliosis and restoration of neuronal integrity in the CA1 region of the hippocampus of the AD rats. These findings implicated that the memantine/rosuvastatin combination could offer a new therapeutic potential for AD management by abrogating the TGF-β1/p-Smad2/p21 pathway and regulating Aβ-clearance.
Correction: MFG-E8 Ameliorates Nerve Injury-Induced Neuropathic Pain by Regulating Microglial Polarization and Neuroinflammation via Integrin β3/SOCS3/STAT3 Pathway in Mice.
Zhang L, Dai X, Li D … +7 more , Wu J, Gao S, Song F, Liu L, Zhou Y, Liu D, Mei W
J Neuroimmune Pharmacol · 2024 Dec · PMID 39704957 · Publisher ↗
Abstract loading — click title to view on PubMed.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe