Displaying publications 1 - 20 of 69 in total

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  1. Fulltext Can Amphotericin B-mediated effects be limited using intranasal versus intravenous route?
    Siddiqui R, Yee Ong TY, Maciver S, Khan NA
    Ther Deliv, 2023 Aug;14(8):485-490.
    PMID: 37691579 DOI: 10.4155/tde-2023-0032
    Aim: CNS infections due to parasites often prove fatal. In part, this is due to inefficacy of drugs to cross the blood-brain barrier. Methods: Here, we tested intranasal and intravenous route and compared adverse effects of Amphotericin B administration, through blood biochemistry, liver, kidney and brain histopathological evidence of toxicities in vivo post-administration. Results: It was observed that intranasal route limits the adverse side effects of Amphotericin B, in contrast to intravenous route. Conclusion: As parasites such as Naegleria fowleri exhibit unequivocal affinity toward the olfactory bulb and frontal lobe in the central nervous system, intranasal administration would directly reach amoebae bypassing the blood-brain barrier selectivity and achieve the minimum inhibitory concentration at the target site.
    Matched MeSH terms: Blood-Brain Barrier*
  2. Nanomedicine facilitated cell signaling blockade: difficulties and strategies to overcome glioblastoma
    Habeeb M, Vengateswaran HT, You HW, Saddhono K, Aher KB, Bhavar GB
    J Mater Chem B, 2024 Feb 14;12(7):1677-1705.
    PMID: 38288615 DOI: 10.1039/d3tb02485g
    Glioblastoma (GBM) is a highly aggressive and lethal type of brain tumor with complex and diverse molecular signaling pathways involved that are in its development and progression. Despite numerous attempts to develop effective treatments, the survival rate remains low. Therefore, understanding the molecular mechanisms of these pathways can aid in the development of targeted therapies for the treatment of glioblastoma. Nanomedicines have shown potential in targeting and blocking signaling pathways involved in glioblastoma. Nanomedicines can be engineered to specifically target tumor sites, bypass the blood-brain barrier (BBB), and release drugs over an extended period. However, current nanomedicine strategies also face limitations, including poor stability, toxicity, and low therapeutic efficacy. Therefore, novel and advanced nanomedicine-based strategies must be developed for enhanced drug delivery. In this review, we highlight risk factors and chemotherapeutics for the treatment of glioblastoma. Further, we discuss different nanoformulations fabricated using synthetic and natural materials for treatment and diagnosis to selectively target signaling pathways involved in GBM. Furthermore, we discuss current clinical strategies and the role of artificial intelligence in the field of nanomedicine for targeting GBM.
    Matched MeSH terms: Blood-Brain Barrier/metabolism
  3. Fulltext Targeted delivery of brain-derived neurotrophic factor for the treatment of blindness and deafness
    Khalin I, Alyautdin R, Kocherga G, Bakar MA
    Int J Nanomedicine, 2015;10:3245-67.
    PMID: 25995632 DOI: 10.2147/IJN.S77480
    Neurodegenerative causes of blindness and deafness possess a major challenge in their clinical management as proper treatment guidelines have not yet been found. Brain-derived neurotrophic factor (BDNF) has been established as a promising therapy against neurodegenerative disorders including hearing and visual loss. Unfortunately, the blood-retinal barrier and blood-cochlear barrier, which have a comparable structure to the blood-brain barrier prevent molecules of larger sizes (such as BDNF) from exiting the circulation and reaching the targeted cells. Anatomical features of the eye and ear allow use of local administration, bypassing histo-hematic barriers. This paper focuses on highlighting a variety of strategies proposed for the local administration of the BDNF, like direct delivery, viral gene therapy, and cell-based therapy, which have been shown to successfully improve development, survival, and function of spiral and retinal ganglion cells. The similarities and controversies for BDNF treatment of posterior eye diseases and inner ear diseases have been analyzed and compared. In this review, we also focus on the possibility of translation of this knowledge into clinical practice. And finally, we suggest that using nanoparticulate drug-delivery systems may substantially contribute to the development of clinically viable techniques for BDNF delivery into the cochlea or posterior eye segment, which, ultimately, can lead to a long-term or permanent rescue of auditory and optic neurons from degeneration.
    Matched MeSH terms: Blood-Brain Barrier/metabolism*
  4. The movement of the dye (disulphine blue) from blood into brain tissue examined by dye method in normal and Plasmodium berghei infected mice
    Migasena P, Maegraith BG
    Med J Malaya, 1968 Mar;22(3):252.
    PMID: 4234391
    Matched MeSH terms: Blood-Brain Barrier*
  5. Utilizing machine learning techniques to predict the blood-brain barrier permeability of compounds detected using LCQTOF-MS in Malaysian Kelulut honey
    Edros R, Feng TW, Dong RH
    SAR QSAR Environ Res, 2023;34(6):475-500.
    PMID: 37409842 DOI: 10.1080/1062936X.2023.2230868
    Current in silico modelling techniques, such as molecular dynamics, typically focus on compounds with the highest concentration from chromatographic analyses for bioactivity screening. Consequently, they reduce the need for labour-intensive in vitro studies but limit the utilization of extensive chromatographic data and molecular diversity for compound classification. Compound permeability across the blood-brain barrier (BBB) is a key concern in central nervous system (CNS) drug development, and this limitation can be addressed by applying cheminformatics with codeless machine learning (ML). Among the four models developed in this study, the Random Forest (RF) algorithm with the most robust performance in both internal and external validation was selected for model construction, with an accuracy (ACC) of 87.5% and 86.9% and area under the curve (AUC) of 0.907 and 0.726, respectively. The RF model was deployed to classify 285 compounds detected using liquid chromatography quadrupole time-of-flight mass spectrometry (LCQTOF-MS) in Kelulut honey; of which, 140 compounds were screened with 94 descriptors. Seventeen compounds were predicted to permeate the BBB, revealing their potential as drugs for treating neurodegenerative diseases. Our results highlight the importance of employing ML pattern recognition to identify compounds with neuroprotective potential from the entire pool of chromatographic data.
    Matched MeSH terms: Blood-Brain Barrier*
  6. Understanding the mechanisms underlying the disruption of the blood-brain barrier in parasitic infections
    Jamil Al-Obaidi MM, Desa MNM
    J Neurosci Res, 2024 Jan;102(1).
    PMID: 38284852 DOI: 10.1002/jnr.25288
    Parasites have a significant impact on the neurological, cognitive, and mental well-being of humans, with a global population of over 1 billion individuals affected. The pathogenesis of central nervous system (CNS) injury in parasitic diseases remains limited, and prevention and control of parasitic CNS infections remain significant areas of research. Parasites, encompassing both unicellular and multicellular organisms, have intricate life cycles and possess the ability to infect a diverse range of hosts, including the human population. Parasitic illnesses that impact the central and peripheral nervous systems are a significant contributor to morbidity and mortality in low- to middle-income nations. The precise pathways through which neurotropic parasites infiltrate the CNS by crossing the blood-brain barrier (BBB) and cause neurological harm remain incompletely understood. Investigating brain infections caused by parasites is closely linked to studying neuroinflammation and cerebral impairment. The exact molecular and cellular mechanisms involved in this process remain incomplete, but understanding the exact mechanisms could provide insight into their pathogenesis and potentially reveal novel therapeutic targets. This review paper explores the underlying mechanisms involved in the development of neurological disorders caused by parasites, including parasite-derived elements, host immune responses, and modifications in tight junctions (TJs) proteins.
    Matched MeSH terms: Blood-Brain Barrier*
  7. Intranasal nanoparticulate delivery systems for neurodegenerative disorders: a review
    Babu SR, Shekara HH, Sahoo AK, Harsha Vardhan PV, Thiruppathi N, Venkatesh MP
    Ther Deliv, 2023 Sep;14(9):571-594.
    PMID: 37691577 DOI: 10.4155/tde-2023-0019
    Neurodegenerative diseases are a significant cause of mortality worldwide, and the blood-brain barrier (BBB) poses a significant challenge for drug delivery. An intranasal route is a prominent approach among the various methods to bypass the BBB. There are different pathways involved in intranasal drug delivery. The drawbacks of this method include mucociliary clearance, enzymatic degradation and poor drug permeation. Novel nanoformulations and intranasal drug-delivery devices offer promising solutions to overcome these challenges. Nanoformulations include polymeric nanoparticles, lipid-based nanoparticles, microspheres, liposomes and noisomes. Additionally, intranasal devices could be utilized to enhance drug-delivery efficacy. Therefore, intranasal drug-delivery systems show potential for treating neurodegenerative diseases through trigeminal or olfactory pathways, which can significantly improve patient outcomes.
    Matched MeSH terms: Blood-Brain Barrier/metabolism
  8. Nanoneurotherapeutics approach intended for direct nose to brain delivery
    Md S, Mustafa G, Baboota S, Ali J
    Drug Dev Ind Pharm, 2015;41(12):1922-34.
    PMID: 26057769 DOI: 10.3109/03639045.2015.1052081
    Brain disorders remain the world's leading cause of disability, and account for more hospitalizations and prolonged care than almost all other diseases combined. The majority of drugs, proteins and peptides do not readily permeate into brain due to the presence of the blood-brain barrier (BBB), thus impeding treatment of these conditions.
    Matched MeSH terms: Blood-Brain Barrier
  9. Fulltext Nanomaterials in Alzheimer's disease treatment: a comprehensive review
    Faiyaz M, Ganayee MA, Akhtar S, Krishnan S, Flora B, Dogra D, et al.
    Front Biosci (Landmark Ed), 2021 10 30;26(10):851-865.
    PMID: 34719210 DOI: 10.52586/4992
    Alzheimer's, a progressive neurodegenerative disease affects brain and neurons through enormous reduction in nerve cell regenerative capacity. Dementia and impairment of cognitive functions are more prevalent in Alzheimer's disease (AD) patients in both industrialized and non-industrialized countries. Various factors play significant role in molecular cascades that leads to neuronal inflammation, dementia and thereby AD progression. Current medications are symptomatic that alleviates pain while lack in absolute cure, urging researchers to explore targets and therapeutics. Interestingly, nanomedicines developed due to the onset of nanotechnology, are being extensively investigated for the treatment of AD. This review presents the advancement in nanotherapeutic strategies, involving the emergence of nanomaterials that offers advantage to pass through the blood-brain barrier and acts as a therapeutic modality against AD.
    Matched MeSH terms: Blood-Brain Barrier
  10. Fulltext Natural Product-based Nanomedicine: Recent Advances and Issues for the Treatment of Alzheimer's Disease
    Woon CK, Hui WK, Abas R, Haron MH, Das S, Lin TS
    Curr Neuropharmacol, 2022;20(8):1498-1518.
    PMID: 34923947 DOI: 10.2174/1570159X20666211217163540
    Alzheimer's disease (AD) affects the elderly and is characterized by progressive neurodegeneration caused by different pathologies. The most significant challenges in treating AD include the inability of medications to reach the brain because of its poor solubility, low bioavailability, and the presence of the blood-brain barrier (BBB). Additionally, current evidence suggests the disruption of BBB plays an important role in the pathogenesis of AD. One of the critical challenges in treating AD is the ineffective treatments and their severe adverse effects. Nanotechnology offers an alternative approach to facilitate the treatment of AD by overcoming the challenges in drug transport across the BBB. Various nanoparticles (NP) loaded with natural products were reported to aid in drug delivery for the treatment of AD. The nano-sized entities of NP are great platforms for incorporating active materials from natural products into formulations that can be delivered effectively to the intended action site without compromising the material's bioactivity. The review highlights the applications of medicinal plants, their derived components, and various nanomedicinebased approaches for the treatment of AD. The combination of medicinal plants and nanotechnology may lead to new theragnostic solutions for the treatment of AD in the future.
    Matched MeSH terms: Blood-Brain Barrier
  11. Fulltext Deciphering the role of nanoparticles for management of bacterial meningitis: an update on recent studies
    Sharma N, Zahoor I, Sachdeva M, Subramaniyan V, Fuloria S, Fuloria NK, et al.
    Environ Sci Pollut Res Int, 2021 Nov;28(43):60459-60476.
    PMID: 34545518 DOI: 10.1007/s11356-021-16570-y
    Meningitis is an inflammation of the protective membranes called meninges and fluid adjacent the brain and spinal cord. The inflammatory progression expands all through subarachnoid space of the brain and spinal cord and occupies the ventricles. The pathogens like bacteria, fungi, viruses, or parasites are main sources of infection causing meningitis. Bacterial meningitis is a life-threatening health problem that which needs instantaneous apprehension and treatment. Nesseria meningitidis, Streptococcus pneumoniae, and Haemophilus flu are major widespread factors causing bacterial meningitis. The conventional drug delivery approaches encounter difficulty in crossing this blood-brain barrier (BBB) and therefore are insufficient to elicit the desired pharmacological effect as required for treatment of meningitis. Therefore, application of nanoparticle-based drug delivery systems has become imperative for successful dealing with this deadly disease. The nanoparticles have ability to across BBB via four important transport mechanisms, i.e., paracellular transport, transcellular (transcytosis), endocytosis (adsorptive transcytosis), and receptor-mediated transcytosis. In this review, we reminisce distinctive symptoms of meningitis, and provide an overview of various types of bacterial meningitis, with a focus on its epidemiology, pathogenesis, and pathophysiology. This review describes conventional therapeutic approaches for treatment of meningitis and the problems encountered by them while transmitting across tight junctions of BBB. The nanotechnology approaches like functionalized polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carrier, nanoemulsion, liposomes, transferosomes, and carbon nanotubes which have been recently evaluated for treatment or detection of bacterial meningitis have been focused. This review has also briefly summarized the recent patents and clinical status of therapeutic modalities for meningitis.
    Matched MeSH terms: Blood-Brain Barrier
  12. The movement of fluorescent isothiocyanate (F.I.T.C.) labelled human albumin from blood into brain tissue examined by fluorescent technique in normal and Plasmodium knowlesi infected Macaca mulatta
    Migasena P, Maegraith BG
    Med J Malaya, 1968 Mar;22(3):251.
    PMID: 4234390
    Matched MeSH terms: Blood-Brain Barrier*
  13. Factor affecting on the movement of protein across the blood: brain: C.S.F. barriers in Plasmodium knowlesi infected Macaca mulatta
    Migasena P, Maegraith BG
    Med J Malaya, 1968 Mar;22(3):251.
    PMID: 4234389
    Matched MeSH terms: Blood-Brain Barrier*
  14. Fulltext Improved Method for the Establishment of an In Vitro Blood-Brain Barrier Model Based on Porcine Brain Endothelial Cells
    Nielsen SSE, Siupka P, Georgian A, Preston JE, Tóth AE, Yusof SR, et al.
    J Vis Exp, 2017 09 24.
    PMID: 28994773 DOI: 10.3791/56277
    The aim of this protocol presents an optimized procedure for the purification and cultivation of pBECs and to establish in vitro blood-brain barrier (BBB) models based on pBECs in mono-culture (MC), MC with astrocyte-conditioned medium (ACM), and non-contact co-culture (NCC) with astrocytes of porcine or rat origin. pBECs were isolated and cultured from fragments of capillaries from the brain cortices of domestic pigs 5-6 months old. These fragments were purified by careful removal of meninges, isolation and homogenization of grey matter, filtration, enzymatic digestion, and centrifugation. To further eliminate contaminating cells, the capillary fragments were cultured with puromycin-containing medium. When 60-95% confluent, pBECs growing from the capillary fragments were passaged to permeable membrane filter inserts and established in the models. To increase barrier tightness and BBB characteristic phenotype of pBECs, the cells were treated with the following differentiation factors: membrane permeant 8-CPT-cAMP (here abbreviated cAMP), hydrocortisone, and a phosphodiesterase inhibitor, RO-20-1724 (RO). The procedure was carried out over a period of 9-11 days, and when establishing the NCC model, the astrocytes were cultured 2-8 weeks in advance. Adherence to the described procedures in the protocol has allowed the establishment of endothelial layers with highly restricted paracellular permeability, with the NCC model showing an average transendothelial electrical resistance (TEER) of 1249 ± 80 Ω cm2, and paracellular permeability (Papp) for Lucifer Yellow of 0.90 10-6 ± 0.13 10-6 cm sec-1 (mean ± SEM, n=55). Further evaluation of this pBEC phenotype showed good expression of the tight junctional proteins claudin 5, ZO-1, occludin and adherens junction protein p120 catenin. The model presented can be used for a range of studies of the BBB in health and disease and, with the highly restrictive paracellular permeability, this model is suitable for studies of transport and intracellular trafficking.
    Matched MeSH terms: Blood-Brain Barrier/metabolism*
  15. Evaluation of pharmacokinetics and blood-brain barrier permeability of mitragynine using in vivo microdialysis technique
    Kong WM, Mohamed Z, Alshawsh MA, Chik Z
    J Pharm Biomed Anal, 2017 Sep 05;143:43-47.
    PMID: 28551311 DOI: 10.1016/j.jpba.2017.05.020
    A microdialysis system coupled with a sensitive ultra-fast liquid chromatography-mass spectrometry (UFLC-MS) method was developed for the pharmacokinetic analysis of mitragynine in rat blood and striatum. Mitragynine is an active alkaloid of Mitragyna speciosa and has been proposed to be used for opioid withdrawal therapy. In this study, chromatographic separation was performed in a gradient elution mode with 0.1% formic acid and acetonitrile on a Zorbax Eclipse C18 column. The mass spectrometric (MS) analysis was carried out in a positive electrospray mode and mitragynine ion (m/z 399.2) was monitored in extracted ion chromatography. A good linearity range was obtained from 10-1000ng/mL with acceptable accuracy and precision parameters. The microdialysate was collected simultaneously from the striatum and the right jugular vein using microdialysis probes. After a single intravenous administration of 10mg/kg mitragynine, mitragynine showed a two-compartmental drug elimination pattern with half-life (T1/2) of approximately 13h. The percent of AUCbrain/AUCplasma of mitragynine was calculated and shown to be 65.8±4.5%. The results indicated that mitragynine could be a suitable molecule to develop into an opioid replacement drug based on its ideal pharmacokinetic properties, namely, small molecular size, lipophilic in nature and with excellent blood-brain barrier (BBB) permeability.
    Matched MeSH terms: Blood-Brain Barrier*
  16. Leakage beyond the primary lesion: A temporal analysis of cerebrovascular dysregulation at sites of hippocampal secondary neurodegeneration following cortical photothrombotic stroke
    Hood RJ, Sanchez-Bezanilla S, Beard DJ, Rust R, Turner RJ, Stuckey SM, et al.
    J Neurochem, 2023 Dec;167(6):733-752.
    PMID: 38010732 DOI: 10.1111/jnc.16008
    We have previously demonstrated that a cortical stroke causes persistent impairment of hippocampal-dependent cognitive tasks concomitant with secondary neurodegenerative processes such as amyloid-β accumulation in the hippocampus, a region remote from the primary infarct. Interestingly, there is emerging evidence suggesting that deposition of amyloid-β around cerebral vessels may lead to cerebrovascular structural changes, neurovascular dysfunction, and disruption of blood-brain barrier integrity. However, there is limited knowledge about the temporal changes of hippocampal cerebrovasculature after cortical stroke. In the current study, we aimed to characterise the spatiotemporal cerebrovascular changes after cortical stroke. This was done using the photothrombotic stroke model targeting the motor and somatosensory cortices of mice. Cerebrovascular morphology as well as the co-localisation of amyloid-β with vasculature and blood-brain barrier integrity were assessed in the cortex and hippocampal regions at 7, 28 and 84 days post-stroke. Our findings showed transient cerebrovascular remodelling in the peri-infarct area up to 28 days post-stroke. Importantly, the cerebrovascular changes were extended beyond the peri-infarct region to the ipsilateral hippocampus and were sustained out to 84 days post-stroke. When investigating vessel diameter, we showed a decrease at 84 days in the peri-infarct and CA1 regions that were exacerbated in vessels with amyloid-β deposition. Lastly, we showed sustained vascular leakage in the peri-infarct and ipsilateral hippocampus, indicative of a compromised blood-brain-barrier. Our findings indicate that hippocampal vasculature may represent an important therapeutic target to mitigate the progression of post-stroke cognitive impairment.
    Matched MeSH terms: Blood-Brain Barrier/metabolism
  17. A proposed cascade of vascular events leading to granulomatous amoebic encephalitis
    Baig AM, Khan NA
    Microb Pathog, 2015 Nov;88:48-51.
    PMID: 26276705 DOI: 10.1016/j.micpath.2015.08.005
    Granulomatous amoebic encephalitis due to Acanthamoeba is a chronic disease that almost always results in death. Hematogenous spread is a pre-requisite followed by amoebae invasion of the blood-brain barrier to enter the central nervous system. Given the systemic nature of this infection, a significant latent period of several months before the appearance of clinical manifestations is puzzling. Based on reported cases, here we propose pathogenetic mechanisms that explain the above described latency of the disease.
    Matched MeSH terms: Blood-Brain Barrier
  18. Effects of Toxoplasma gondii infection on the function and integrity of human cerebrovascular endothelial cells and the influence of verapamil treatment in vitro
    Harun MSR, Marsh V, Elsaied NA, Webb KF, Elsheikha HM
    Brain Res, 2020 11 01;1746:147002.
    PMID: 32592740 DOI: 10.1016/j.brainres.2020.147002
    Toxoplasma gondii can cause parasitic encephalitis, a life-threatening infection that predominately occurs in immunocompromised individuals. T. gondii has the ability to invade the brain, but the mechanisms by which this parasite crosses the blood-brain-barrier (BBB) remain incompletely understood. The present study reports the changes associated with infection and replication of T. gondii within human brain microvascular endothelial cells (BMECs) in vitro. Our results indicated that exposure to T. gondii had an adverse impact on the function and integrity of the BMECs - through induction of cell cycle arrest, disruption of the BMEC barrier integrity, reduction of cellular viability and vitality, depolarization of the mitochondrial membrane potential, increase of the DNA fragmentation, and alteration of the expression of immune response and tight junction genes. The calcium channel/P-glycoprotein transporter inhibitor verapamil was effective in inhibiting T. gondii crossing the BMECs in a dose-dependent manner. The present study showed that T. gondii can compromise several functions of BMECs and demonstrated the ability of verapamil to inhibit T. gondii crossing of the BMECs in vitro.
    Matched MeSH terms: Blood-Brain Barrier/drug effects; Blood-Brain Barrier/metabolism; Blood-Brain Barrier/physiopathology*
  19. A Molecular Approach to Epilepsy Management: from Current Therapeutic Methods to Preconditioning Efforts
    Amini E, Rezaei M, Mohamed Ibrahim N, Golpich M, Ghasemi R, Mohamed Z, et al.
    Mol Neurobiol, 2015 Aug;52(1):492-513.
    PMID: 25195699 DOI: 10.1007/s12035-014-8876-5
    Epilepsy is the most common and chronic neurological disorder characterized by recurrent unprovoked seizures. The key aim in treating patients with epilepsy is the suppression of seizures. An understanding of focal changes that are involved in epileptogenesis may therefore provide novel approaches for optimal treatment of the seizure. Although the actual pathogenesis of epilepsy is still uncertain, recently growing lines of evidence declare that microglia and astrocyte activation, oxidative stress and reactive oxygen species (ROS) production, mitochondria dysfunction, and damage of blood-brain barrier (BBB) are involved in its pathogenesis. Impaired GABAergic function in the brain is probably the most accepted hypothesis regarding the pathogenesis of epilepsy. Clinical neuroimaging of patients and experimental modeling have demonstrated that seizures may induce neuronal apoptosis. Apoptosis signaling pathways are involved in the pathogenesis of several types of epilepsy such as temporal lobe epilepsy (TLE). The quality of life of patients is seriously affected by treatment-related problems and also by unpredictability of epileptic seizures. Moreover, the available antiepileptic drugs (AED) are not significantly effective to prevent epileptogenesis. Thus, novel therapies that are proficient to control seizure in people who are suffering from epilepsy are needed. The preconditioning method promises to serve as an alternative therapeutic approach because this strategy has demonstrated the capability to curtail epileptogenesis. For this reason, understanding of molecular mechanisms underlying brain tolerance induced by preconditioning is crucial to delineate new neuroprotective ways against seizure damage and epileptogenesis. In this review, we summarize the work to date on the pathogenesis of epilepsy and discuss recent therapeutic strategies in the treatment of epilepsy. We will highlight that novel therapy targeting such as preconditioning process holds great promise. In addition, we will also highlight the role of gene reprogramming and mitochondrial biogenesis in the preconditioning-mediated neuroprotective events.
    Matched MeSH terms: Blood-Brain Barrier/drug effects; Blood-Brain Barrier/pathology
  20. Loss of Transfected Human Brain Micro-Vascular Endothelial Cell Integrity during Herpes Simplex Virus Infection
    Lee SH, Atiya N, Wang SM, Manikam R, Raju CS, Sekaran SD
    Intervirology, 2018;61(4):193-203.
    PMID: 30541013 DOI: 10.1159/000495180
    OBJECTIVE: Herpes simplex virus infection through the neuronal route is the most well-studied mode of viral encephalitis that can persists in a human host for a lifetime. However, the involvement of other possible infection mechanisms by the virus remains underexplored. Therefore, this study aims to determine the temporal effects and mechanisms by which the virus breaches the human brain micro-vascular endothelial cells of the blood-brain barrier.

    METHOD: An electrical cell-substrate impedance-sensing tool was utilized to study the real-time cell-cell barrier or morphological changes in response to the virus infection.

    RESULTS: Herpes simplex virus, regardless of type (i.e., 1 or 2), reduced the cell-cell barrier resistance almost immediately after virus addition to endothelial cells, with negligible involvement of cell-matrix adhesion changes. There is no exclusivity in the infection ability of endothelial cells. From 30 h after HSV infection, there was an increase in cell membrane capacitance with a subsequent loss of cell-matrix adhesion capability, indicating a viability loss of the infected endothelial cells.

    CONCLUSION: This study shows for the first time that destruction of human brain micro-vascular endothelial cells as an in vitro model of the blood-brain barrier could be an alternative invasion mechanism during herpes simplex virus infection.

    Matched MeSH terms: Blood-Brain Barrier/physiology*; Blood-Brain Barrier/virology*
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