Therapeutic effects of ellagic acid on memory, hippocampus electrophysiology deficits, and elevated TNF-α level in brain due to experimental traumatic brain injury

Document Type : Original Article

Authors

1 Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences, Golestan Blvd, Ahvaz, Iran

2 Department of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Golestan Blvd, Ahvaz, Iran

3 Department of Immunology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Golestan Blvd, Ahvaz, Iran

Abstract

Objective(s): Cognitive defects such as learning and memory impairment are amongst the most repetitious sequelae after sever and moderate traumatic brain injury (TBI). It was suggested that ellagic acid (EA), an innate phenol product, display neuroprotective properties against oxidative and inflammatory damages after brain injury. The object of the current study was therapeutic properties of EA on blood-brain barrier (BBB) interruption and elevated content of TNF-α in brain tissue followed by neurologic aftereffects, cognitive and brain electrophysiology deficits as outcomes of diffuse TBI in rat.
Materials and Methods: TBI was induced by a 200 g weight falling by a 2-m height through a free-falling tube onto the head of anesthetized rat. TBI rats treated immediately after trauma with EA             (100 mg/kg, IP) once every 8 hr until 48 hr later. Neurologic outcomes, passive avoidance task (PAT), hippocampal long-term potentiation (LTP), BBB permeability and content of TNF-α in brain tissue were evaluated.
Results: TBI induced significant impairments in neurological score, BBB function, PAT and hippocampal LTP in TBI+Veh group in compare with Sham+Veh (P<0.001). EA treatment decreased neurologic severity score (NSS), restored increased BBB permeability, cognitive and hippocampal LTP abnormalities, and elevated brain content of TNF-α due to TBI significantly (P<0.001).
Conclusion: Our findings propose that EA can restore NSS, cognitive and LTP deficits and prevent brain inflammation may by restore BBB permeability as well as lowering brain content of TNF-α following TBI.

Keywords

References

1. Al Nimer F, Lindblom R, Ström M, Guerreiro-Cacais AO, Parsa R, Aeinehband S, et al. Strain influences on inflammatory pathway activation, cell infiltration and complement cascade after traumatic brain injury in the rat. Brain Behav Immun 2013; 27:109-122.
2.Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 2006; 3:1-20.
3.Kalsotra A, Zhao J, Anakk S, Dash PK, Strobel HW. Brain trauma leads to enhanced lung inflammation and injury: evidence for role of P4504Fs in resolution. J Cereb Blood Flow Metab 2007; 27:963-974.
4.Kumar A, Loane D. Neuroinflammation after traumatic brain injury: opportunities for therapeutic intervention. Brain Behav Immun 2012; 26:1191-1201.
5.Shlosberg D, Benifla M, Kaufer D, Friedman A. Blood–brain barrier breakdown as a therapeutic target in traumatic brain injury. Nat Rev Neurol 2010; 6:393-403.
6.Ramlackhansingh AF, Brooks DJ, Greenwood RJ, Bose SK, Turkheimer FE, Kinnunen KM, et al. Inflammation after trauma: microglial activation and traumatic brain injury. Ann Neurol 2011; 70:374-383.
7.Ribbers GM. Brain Injury: Long term outcome after traumatic brain injury. In: Stone JH, Blouin M. editors. Int Encyclopedia of Rehabilitation [serial online] 2010:1-9.Available from: http://cirrie.buffalo.edu/encyclopedia/en/article/338/.
8.Newman DJ, Cragg GM. Natural Products as Sources of New Drugs over the Last 25 Years. J Nat Prod 2007 ; 70:461-477.
9.Morton LW, Abu-Amsha Caccetta R, Puddey IB, Croft KD. Chemistry and biological effects of dietary phenolic compounds: relevance to cardiovascular disease. Clin Exp Pharmacol Physiol 2000; 27:152-159.
10.Ben Nasr C, Ayed N, Metche M. Quantitative determination of the polyphenolic content of pomegranate peel. Z Lebensm Unters Forsch 1996; 203:374-378.
11.Kostrzewa RM, Segura-Aguilar J. Novel mechanisms and approaches in the study of neurodegeneration and neuroprotection. A review. Neurotox Res 2003; 5:375-383.
12.Clifford MN, Scalbert A. Ellagitannins–nature, occurrence and dietary burden. J Sci Food Agric 2000; 80:1118-1125.
13.Wada L, Ou B. Antioxidant activity and phenolic content of Oregon caneberries. J Agric Food Chem 2002; 50:3495-500.
14.Atta-Ur-Rahman F, Ngounou M, Choudhary M, Malik S, Makhmoor T, Nur-E-Alam M, et al. New antioxidant and antimicrobial ellagic acid derivatives from Pteleopsis hylodendron. Planta Med 2001 ; 67:335-339.
15.Chen HS, Liu M, Shi LJ, Zhao JL, Zhang CP, Lin LQ, et al. Effects of raspberry phytochemical extract on cell proliferation, apoptosis, andserum proteomics in a rat model. J Food Sci 2011; 76:T192-T198.
16.Festa F, Aglitti T, Duranti G, Ricordy R, Perticone P, Cozzi R. Strong antioxidant activity of ellagic acid in mammalian cells in vitro revealed by the comet assay. Anticancer Res 2001; 21:3903-3908.
17.Uzar E, Alp H, Cevik MU, Fırat U, Evliyaoglu O, Tufek A, et al. Ellagic acid attenuates oxidative stress on brain and sciatic nerve and improves histopathology of brain in streptozotocin-induced diabetic rats. Neurol Sci 2012; 33:567-574.
18.Narayanan BA, Geoffroy O, Willingham MC, Re GG, Nixon DW. p53/p21 (WAF1/CIP1) expression and its possible role in G1 arrest and apoptosis in ellagic acid treated cancer cells. Cancer Lett 1999; 136:215-221.
19.Selig DK, Segal MR, Liao D, Malenka RC, Malinow R, Nicoll RA, et al. Examination of the role of cGMP in long-term potentiation in the CA1 region of the hippocampus. Learn Mem 1996; 3:42-48.
20.Baldwin SA, Gibson T, Callihan CT, Sullivan PG, Palmer E, Scheff SW. Neuronal cell loss inthe CA3 subfield of the hippocampus following cortical contusion utilizing the optical disector method for cell counting. J Neurotrauma1997; 14:385-398.
21.Colicos MA, Dixon CE, Dash PK. Delayed, selective neuronal death following experimental cortical impact injury in rats: possible role in memory deficits. Brain Res 1996; 739:111-119.
22.Huh JW, Widing AG, Raghupathi R. Differential effects of injury severity on cognition and cellular pathology after contusive brain trauma in the immature rat. J Neurotrauma 2011; 28:245-257.
23.Huh JW, Widing AG, Raghupathi R. Midline brain injury in the immature rat induces sustainedcognitive deficits, bihemispheric axonal injury and neuro-degeneration. Exp Neurol 2008; 213:84-92.
24. Frankola KA, Greig NH, Luo W, Tweedie D. Targeting TNF-alpha to elucidate and ameliorate neuroinflammation in neurodegenerative diseases. CNS Neurol Disord DrugTargets 2011; 10:391–403.
25.Pickering M, Cumiskey D, O'Connor JJ. Actions of TNF‐α on glutamatergic synaptic transmission in the central nervous system. Exp. Physiol 2005; 90:663-670.
26.Rogerio AP, Fontanari C, Melo MC, Ambrosio SR, Souza GE, Pereira PS, et al. Anti‐inflammatory, analgesic and anti‐oedematouseffects of Lafoensia pacari extract and ellagic acid. J Pharm Pharmacol 2006; 58:1265-1273.
27.Montgomery SL, Bowers WJ. Tumor necrosis factor-alpha and the roles it plays in homeostatic and degenerative processes within the central nervous system. J Neuroimmune Pharmacol 2012; 7:42-59.
28. Farbood Y,  Sarkaki A, Dianat M, Khodadadi A, Haddad MK, Mashhadizadeh, S. Ellagic acid prevents cognitive and hippocampal long-term potentiation deficits and brain inflammation in rat with traumatic brain injury. Life Sci 2015; 124:120-127.
29.Mansouri MT, Naghizadeh B, Ghorbanzadeh B, Farbood Y. Central and peripheral antinociceptive effects of ellagic acid in different animal models of pain. Eur J Pharmacol 2013; 707:46-53.
30. Abdul-Wahab RH, Al-Momani WM, Janakat S, Oran SA. Bioavailability of ellagic acid after single dose administration using HPLC. Pak J Nut 2009; 8:1661-1664
31.Marmarou A, Foda MA, van den Brink W, Campbell J, Kita H, Demetriadou K. A new model of diffuse brain injury in rats: Part I: Pathophysiology and biomechanics. J Neurosurg 1994; 80:291-300.
32.Khaksari M, Soltani Z, Shahrokhi N, Moshtaghi G, Asadikaram G. The role of estrogen and progesterone, administered alone and in combination, in modulating cytokine concentration following traumatic brain injury. Can J Physiol Pharmacol 2011; 89:31-40.
33.Lashgari R, Motamedi F, Asl SZ, Shahidi S, Komaki A. Behavioral and electrophysiological studies of chronic oral administration of L-type calcium channel blocker verapamil on learning and memory in rats. Behav Brain Res 2006; 171:324-328.
34.Paxinos G, Watson C. The rat brain in stereotaxic coordinates: hard cover. 6thed. Academic Press; 2006.
35.Gureviciene I, Ikonen S, Gurevicius K, Sarkaki A, van Groen T, Pussinen R, et al. Normal induction but accelerated decay of LTP in APP + PS1 transgenic mice. Neurobiol Dis 2004; 15:188-195.
36.Sarkaki A, Fathimoghaddam H, Mansouri SMT, Shahrani Korrani M, Farbood Y. Gallic acid improves cognitive, hippocampal long-term potentiation deficits and brain damage induced by chronic cerebral hypoperfusion in rats. Pak J Biol Sci 2014; 17:978-990.
37.Sarkaki A, Assaei R, Motamedi F, Badavi M, Pajouhi N. Effect of parental morphine addiction on hippocampal long-term potentiation in rats offspring. Behav Brain Res 2008; 186:72-77.
38.Sarkaki A, Khaksari Haddad M, Soltani Z, Shahrokhi N, Mahmoodi M. Time-and dose-dependent neuroprotective effects of sex steroid hormones on inflammatory cytokines after a traumatic brain injury. J Neurotrauma 2013; 30:47-54.
39.O'Connor CA, Cernak I, Vink R. Both estrogen and progesterone attenuate edema formation following diffuse traumatic brain injury in rats. Brain Res 2005; 1062:171-174.
40.Khaksari M, Mahmmodi R, Shahrokhi N, Shabani M, Joukar S, Aqapour M. The effects of shilajit on brain edema, intracranial pressure and neurologic outcomes following the traumatic brain injury in rat. Iran J Basic Med Sci. 2013; 16:858-864
41.King DR, Cohn SM, Proctor KG. Changes in intracranial pressure, coagulation, and neurologic outcome after resuscitation from experimental traumatic brain injury with hetastarch. Surgery 2004; 136:355-363.
42.Sternbach GL. The Glasgow coma scale. J Emerg Med 2000; 19:67-71.
43.Reeves TM, Lyeth BG, Povlishock JT. Long-term potentiation deficits and excitability changes following traumatic brain injury. Exp Brain Res1995; 106:248-256.
44.Sanders MJ, Sick TJ, Perez-Pinzon MA, Dietrich WD, Green EJ. Chronic failure in the maintenance of long-term potentiation following fluid percussion injury in the rat. Brain Res 2000; 861:69-76.
45.Chao PC, Hsu CC, Yin MC. Anti-inflammatory and anti-coagulatory activities of caffeic acid and ellagic acid in cardiac tissue of diabetic mice. Nutr Metab (Lond) 2009; 6:1-8.
46.Santello M, Volterra A. TNFα in synaptic function: switching gears. Trends Neurosci 2012; 35:638-647.
47.Beattie EC, Stellwagen D, Morishita W, Bresnahan JC, Ha BK, Von Zastrow M, et al. Control of synaptic strength by glial TNFα. Science 2002; 295:2282-2285.
48.Kaneko M, Stellwagen D, Malenka RC, Stryker MP. Tumor necrosis factor-α mediates one component of competitive, experience-dependent plasticity in developing visual cortex. Neuron 2008;58:673-680.
49.Baune BT, Wiede F, Braun A, Golledge J, Arolt V, Koerner H. Cognitive dysfunction in mice deficient for TNF‐α and its receptors. Am J Med Genet Bneuro-psychiatr Genet 2008; 147B:1056-1064.
50.Beste C, Baune BT, Falkenstein M, Konrad C. variations in the TNF-Gene (TNF--308G¡ A) affect attention and action selection mechanisms in a dissociated fashion. J Neurophysiol 2010; 104:2523-2531.
51.Santello M, Bezzi P, Volterra A. TNF-α controls glutamatergic gliotransmission in the hippocampal dentate gyrus. Neuron 2011; 69:988-1001.
52.McCoy MK, Tansey MG. TNF signaling inhibition in the CNS: implications for normal brain function and neurodegenerativedisease. J Neuroinflamm 2008; 5:1-13.
53.Frankola KA, Greig NH, Luo W, Tweedie D. Targeting TNF-alpha to elucidate and ameliorate neuroinflammation in neurodegenerative diseases. CNS Neurol Disord Drug Targets 2011; 10:391-403.
54.Wyss-CorayT, Mucke L. Inflammation in neurodegenerative disease—a double-edged sword. Neuron 2002; 35:419-432.
55.Goodman JC, Robertson CS, Grossman RG, Narayan RK. Elevation of tumor necrosis factor in head injury. J Neuroimmunol 1990; 30:213-217.
56.Olmos G, Lladó J. Tumor necrosis factor alpha: A link between neuroinflammation and excitotoxicity. Mediators Inflamm 2014; 2014:861231.
57.Liu T, Clark R, McDonnell P, Young P, White R, Barone F, et al. Tumor necrosis factor-alpha expression in ischemic neurons. Stroke 1994; 25:1481-1488.
58.Álvarez A, Cacabelos R, Sanpedro C, García-Fantini M, Aleixandre M. Serum TNF-alpha levels are increased and correlate negatively with free IGF-I in Alzheimer disease. Neurobiol Aging 2007; 28:533-536.
59.BabuGN, Kumar A, Chandra R, Puri S, Kalita J, Misra U. Elevated inflammatory markers in a group of amyotrophic lateral sclerosis patients from northern India. Neurochem Res 2008; 33:1145-1149.
60.Allan SM, Rothwell NJ. Cytokines and acute neurodegeneration. Nat Rev Neurosci 2001; 2:734-744.
61.Wang X, Yue TL, Barone FC, White RF, Gagnon RC, Feuerstein GZ. Concomitant cortical expression of TNF-α and IL-1β mRNAs follows early response gene expression in transient focal ischemia. Mol Chem Neuropathol 1994; 23:103-114.
62.Boka G, Anglade P, Wallach D, Javoy-Agid F, Agid Y, Hirsch E. Immunocytochemical analysis of tumor necrosis factor and its receptors in Parkinson's disease. Neurosci Lett 1994; 172:151-154.
63.Golan H, Levav T, Mendelsohn A, Huleihel M. Involvement of tumor necrosis factor alpha in hippocampal development and function. Cereb Cortex 2004; 14:97-105.
64.Yang L, Lindholm K, Konishi Y, Li R, Shen Y. Target depletion of distinct tumor necrosis factor receptor subtypes reveals hippocampal neuron death and survival through different signal transduction pathways. J Neurosc 2002; 22:3025-3032.
65.Tancredi V, D'Arcangelo G, Grassi F, Tarroni P, Palmieri G, Santoni A, et al. Tumor necrosis factor alters synaptic transmission in rat hippocampal slices. Neurosci Lett 1992; 146:176-178.
66.Butler M, O'connor J, Moynagh P. Dissection of tumor-necrosis factor-α inhibition of long-term potentiation (LTP) reveals a p38 mitogen-activated protein kinase-dependent mechanism which maps to early—but not late—phase LTP. Neuroscience 2004; 124:319-326.
67.Stellwagen D, Beattie EC, Seo JY, Malenka RC. Differential regulation of AMPA receptor and GABA receptor trafficking by tumor necrosis factor-α. J Neurosci 2005; 25:3219-3228.
68.Floden AM, Li S, Combs CK. β-Amyloid-stimulated microglia induce neuron death via synergistic stimulation of tumor necrosis factor α and NMDA receptors. J Neurosci 2005; 25:2566-2575.
69.O'Connor JJ, Moynagh PN, Butler MP, Cumiskey D. The inhibitory effect of tumour necrosis factor-α on long-term potentiation is attenuated by type 1 metabotropic glutamate receptor blockade. Brain Res 2005; 1062:171-174.
70.Umesalma S, Sudhandiran G. Differential inhibitory effects of the polyphenol ellagic acid on inflammatory mediators NF‐κB, iNOS, COX‐2, TNF‐α, and IL‐6 in 1, 2‐dimethylhydrazine‐induced rat colon carcinogenesis. Basic Clin Pharmacol Toxicol 2010; 107:650-655.
71.Yu YM, Chang WC, Wu CH, Chiang SY. Reduction of oxidative stress and apoptosis in hyperlipidemic rabbits by ellagic acid. J Nutr Biochem 2005; 16:675-681.
Iranian Journal of Basic Medical Sciences
Volume 20, Issue 4
April 2017
Pages 399-407

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