Anti-inflammatory and antioxidative effects of elderberry diet in the rat model of seizure: a behavioral and histological investigation on the hippocampus

The present study was designed to evaluate whether elderberry (EB) effectively reduces inflammation and oxidative stress in hippocampal cells to modify seizure damage. Seizure was induced in rats by the injection of pentylenetetrazol (PTZ). In the Seizure + EB group, EB powder was added to the rats’ routine diet for eight consecutive weeks. The study included several behavioral tests, immunohistopathology, Voronoi tessellation (to estimate the spatial distribution of cells in the hippocampus), and Sholl analysis. The results in the Seizure + EB group showed an improvement in the behavioral aspects of the study, a reduction in astrogliosis, astrocyte process length, number of branches, and intersections distal to the soma in the hippocampus of rats compared to controls. Further analysis showed that EB diet increased nuclear factor-like 2 expression and decreased caspase-3 expression in the hippocampus in the Seizure + EB group. In addition, EB protected hippocampal pyramidal neurons from PTZ toxicity and improved the spatial distribution of hippocampal neurons in the pyramidal layer and dentate gyrus. The results of the present study suggest that EB can be considered a potent modifier of astrocyte reactivation and inflammatory responses.

[1]  Hojjat Allah Abbaszadeh,et al.  Inflammatory Response Leads to Neuronal Death in Human Post-Mortem Cerebral Cortex in Patients with COVID-19 , 2021, ACS chemical neuroscience.

[2]  M. Abdollahifar,et al.  Elderberry diet ameliorates motor function and prevents oxidative stress-induced cell death in rat models of Huntington disease , 2021, Brain Research.

[3]  M. Abdollahifar,et al.  Long-Term Effects of Hippocampal Low-Frequency Stimulation on Pro-Inflammatory Factors and Astrocytes Activity in Kindled Rats , 2021, Cell journal.

[4]  Qing Wang,et al.  Astrocytes: a double-edged sword in neurodegenerative diseases , 2021, Neural regeneration research.

[5]  Shwu-Fen Chang,et al.  Transcranial photobiomodulation attenuates pentylenetetrazole‐induced status epilepticus in peripubertal rats , 2020, Journal of biophotonics.

[6]  R. Bernard-Valnet,et al.  Area postrema syndrome: Another feature of anti-GFAP encephalomyelitis , 2020, Multiple sclerosis.

[7]  William A Mills,et al.  Potassium and glutamate transport is impaired in scar-forming tumor-associated astrocytes , 2019, Neurochemistry International.

[8]  R. Faull,et al.  The Role of Microglia and Astrocytes in Huntington’s Disease , 2019, Front. Mol. Neurosci..

[9]  Tae-Hoo Yi,et al.  Sambucus nigra L. ameliorates UVB-induced photoaging and inflammatory response in human skin keratinocytes , 2019, Cytotechnology.

[10]  J. Álvarez-Sabín,et al.  Etiology, seizure type, and prognosis of epileptic seizures in the emergency department , 2019, Epilepsy & Behavior.

[11]  Ji-Young Lee,et al.  Long‐Term Supplementation of Black Elderberries Promotes Hyperlipidemia, but Reduces Liver Inflammation and Improves HDL Function and Atherosclerotic Plaque Stability in Apolipoprotein E‐Knockout Mice , 2018, Molecular nutrition & food research.

[12]  Iekhsan Othman,et al.  Orthosiphon stamineus Leaf Extract Affects TNF-α and Seizures in a Zebrafish Model , 2018, Front. Pharmacol..

[13]  Shanshan Zhang,et al.  Gastrodin Suppresses Pentylenetetrazole-Induced Seizures Progression by Modulating Oxidative Stress in Zebrafish , 2018, Neurochemical Research.

[14]  S. Okada,et al.  Astrocyte reactivity and astrogliosis after spinal cord injury , 2018, Neuroscience Research.

[15]  G. Łysiak,et al.  Bioactive properties of Sambucus nigra L. as a functional ingredient for food and pharmaceutical industry , 2017, Journal of Functional Foods.

[16]  L. Moons,et al.  Characterizing microglia activation: a spatial statistics approach to maximize information extraction , 2017, Scientific Reports.

[17]  C. Henneberger.  Does rapid and physiological astrocyte–neuron signalling amplify epileptic activity? , 2017, The Journal of physiology.

[18]  A. Orekhov,et al.  Anti-cytokine therapy for prevention of atherosclerosis. , 2016, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[19]  J. Hernández-Damián,et al.  Overview of Nrf2 as Therapeutic Target in Epilepsy , 2015, International journal of molecular sciences.

[20]  Andrew L. Thomas,et al.  Inhibition of microglial activation by elderberry extracts and its phenolic components. , 2015, Life sciences.

[21]  E. Basch,et al.  An Evidence-Based Systematic Review of Elderberry and Elderflower (Sambucus nigra) by the Natural Standard Research Collaboration , 2014, Journal of dietary supplements.

[22]  M. Siebes,et al.  Perfusion territories subtended by penetrating coronary arteries increase in size and decrease in number toward the subendocardium. , 2014, American journal of physiology. Heart and circulatory physiology.

[23]  Tim David,et al.  A Computational Model of Oxygen Transport in the Cerebrocapillary Levels for Normal and Pathologic Brain Function , 2013, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[24]  G. Mann,et al.  Temporal and spatial distribution of Nrf2 in rat brain following stroke: quantification of nuclear to cytoplasmic Nrf2 content using a novel immunohistochemical technique , 2013, The Journal of physiology.

[25]  Josemir W Sander,et al.  The long-term risk of premature mortality in people with epilepsy. , 2011, Brain : a journal of neurology.

[26]  Zheng Zachory Wei,et al.  Astrocytes: implications for neuroinflammatory pathogenesis of Alzheimer's disease. , 2011, Current Alzheimer research.

[27]  Dennis D. Spencer,et al.  Astrocytes and epilepsy , 2010, Neurotherapeutics.

[28]  M. Fujimoto,et al.  Autoantibody against caspase-3, an executioner of apoptosis, in patients with systemic sclerosis , 2010, Rheumatology International.

[29]  A. Czurkó,et al.  The mode of death of epilepsy-induced “dark” neurons is neither necrosis nor apoptosis: An electron-microscopic study , 2008, Brain Research.

[30]  D. Catarzi,et al.  Competitive AMPA receptor antagonists , 2007, Medicinal research reviews.

[31]  F. Gallyas,et al.  Pathological circumstances impair the ability of “dark” neurons to undergo spontaneous recovery , 2006, Brain Research.

[32]  S. Torquato,et al.  Random Heterogeneous Materials: Microstructure and Macroscopic Properties , 2005 .

[33]  R. Prior,et al.  Characterization of anthocyanins and proanthocyanidins in some cultivars of Ribes, Aronia, and Sambucus and their antioxidant capacity. , 2004, Journal of agricultural and food chemistry.

[34]  S R Nelson,et al.  Soman‐induced seizures: limbic activity, oxidative stress and neuroprotective proteins , 2001, Journal of applied toxicology : JAT.

[35]  R. Kothari,et al.  Emergency department management of patients with seizures: a multicenter study. , 2001, Academic emergency medicine : official journal of the Society for Academic Emergency Medicine.

[36]  G. Godefroy,et al.  Voronoi tessellation to study the numerical density and the spatial distribution of neurones , 2000, Journal of Chemical Neuroanatomy.

[37]  J. Quevedo,et al.  Lipid peroxidation in hippocampus early and late after status epilepticus induced by pilocarpine or kainic acid in Wistar rats , 2000, Neuroscience Letters.

[38]  R. Simon,et al.  Involvement of Caspase‐3‐Like Protease in the Mechanism of Cell Death Following Focally Evoked Limbic Seizures , 2000, Journal of neurochemistry.

[39]  Simon C Watkins,et al.  Increases in Bcl‐2 and cleavage of caspase‐1 and caspase‐3 in human brain after head injury , 1999, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[40]  J B Schulz,et al.  Caspases as treatment targets in stroke and neurodegenerative diseases , 1999, Annals of neurology.

[41]  Y. Lazebnik,et al.  Caspases: enemies within. , 1998, Science.

[42]  R. Simon,et al.  Induction of Caspase-3-Like Protease May Mediate Delayed Neuronal Death in the Hippocampus after Transient Cerebral Ischemia , 1998, The Journal of Neuroscience.

[43]  M. Moskowitz,et al.  Activation and Cleavage of Caspase-3 in Apoptosis Induced by Experimental Cerebral Ischemia , 1998, The Journal of Neuroscience.

[44]  T. Murakami,et al.  Dark neurons in the mouse brain: an investigation into the possible significance of their variable appearance within a day and their relation to negatively charged cell coats. , 1996, Archives of histology and cytology.

[45]  A. Becker,et al.  N ω-nitro-l-arginine methyl ester interferes with pentylenetetrazol-induced kindling and has no effect on changes in glutamate binding , 1995, Brain Research.

[46]  W. Hauser,et al.  Incidence of Acute Symptomatic Seizures in Rochester, Minnesota, 1935‐1984 , 1995, Epilepsia.

[47]  J. Röhrenbeck,et al.  Immunocytochemical staining of AII‐amacrine cells in the rat retina with antibodies against parvalbumin , 1993, The Journal of comparative neurology.

[48]  W. Hauser,et al.  Incidence of Epilepsy and Unprovoked Seizures in Rochester, Minnesota: 1935–1984 , 1993, Epilepsia.

[49]  Yang Li,et al.  Morphological and functional alterations of astrocytes responding to traumatic brain injury , 2019, Journal of Integrative Neuroscience.

[50]  Suzana Lima de Oliveira,et al.  O papel da dieta cetogênica no estresse oxidativo presente na epilepsia experimental , 2011 .

[51]  Y. Olsson,et al.  The temporal evolution of hypoglycemic brain damage , 2004, Acta Neuropathologica.

[52]  F. Gallyas,et al.  “Dark” (compacted) neurons may not die through the necrotic pathway , 2004, Experimental Brain Research.

[53]  J. Swann,et al.  Spine loss and other dendritic abnormalities in epilepsy , 2000, Hippocampus.

[54]  P. Sterling.  The Synaptic Organization of the Brain , 1998 .