Selective Reduction of Brain Docosahexaenoic Acid after Experimental Brain Injury and Mitigation of Neuroinflammatory Outcomes with Dietary DHA

Abstract

Background Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is important for brain development and function, but the interactions of dietary DHA with fatty acid profiles, sensory sensitivities, and inflammation that may change after traumatic brain injury (TBI) are poorly understood. It is also unknown whether DHA alters experimental TBI outcomes measured more than 2 weeks after injury. The current study investigated whether dietary DHA, provided before (PreDHA) or after (PostDHA) experimental TBI, would improve outcomes for up to 24 days after injury.

Methods Rats consumed predetermined diets for 28 days prior to midline fluid percussion injury (mFPI) or to sham surgery. The effects of PreDHA, TBI, and PostDHA on comprehensive fatty acid profiles, neuroinflammation, sensory sensitivity, and spatial learning were then evaluated.

Results The results provided novel evidence that TBI selectively reduced brain DHA content, as injury did not decrease any other fatty acid that was measured. Furthermore, PreDHA and PostDHA attenuated injury-induced increases in sensory sensitivity as well as in tumor necrosis factor-α (TNF-α), interleukin-10, and interleukin-1β in the somatosensory cortex. However, [³H]PK11195 autoradiography showed that PostDHA was more effective than PreDHA in reducing microglial/macrophage activation in the somatosensory cortex, hippocampus, and substantia nigra. Spatial learning outcomes were largely unaffected by diet or injury, but PostDHA was associated with shorter swimming distances in the Morris water maze (MWM) at 15 days post-injury.

Conclusion Overall, sufficient DHA intake may be necessary to replace DHA that is lost to TBI and may improve some symptoms of post-concussive syndrome (PCS) over an extended period through inflammation-related mechanisms.

Keywords

traumatic brain injury - docosahexaenoic acid - neuroinflammation - post-concussive syndrome

• References

• 1 Faul M, Xu L, Wald MM, Coronado VG. Traumatic Brain Injury in the United States: Emergency Department Visits, Hospitalizations and Deaths 2002–2006. N.C.f.I.P.a.C. Centers for Disease Control and Prevention; 2010
• 2 Potter SD, Brown RG, Fleminger S. Randomised, waiting list controlled trial of cognitive-behavioural therapy for persistent postconcussional symptoms after predominantly mild-moderate traumatic brain injury. J Neurol Neurosurg Psychiatry 2016; 87 (10) 1075-1083
• 3 Goodrich GL, Flyg HM, Kirby JE, Chang CY, Martinsen GL. Mechanisms of TBI and visual consequences in military and veteran populations. Optom Vis Sci 2013; 90 (02) 105-112
• 4 Goodrich GL, Martinsen GL, Flyg HM, Kirby J, Garvert DW, Tyler CW. Visual function, traumatic brain injury, and posttraumatic stress disorder. J Rehabil Res Dev 2014; 51 (04) 547-558
• 5 Albensi BC, Janigro D. Traumatic brain injury and its effects on synaptic plasticity. Brain Inj 2003; 17 (08) 653-663
• 6 Arciniegas DB, Topkoff J, Silver JM. Neuropsychiatric Aspects of Traumatic Brain Injury. Curr Treat Options Neurol 2000; 2 (02) 169-186
• 7 Masel BE, DeWitt DS. Traumatic brain injury: a disease process, not an event. J Neurotrauma 2010; 27 (08) 1529-1540
• 8 Werner C, Engelhard K. Pathophysiology of traumatic brain injury. Br J Anaesth 2007; 99 (01) 4-9
• 9 Csuka E, Morganti-Kossmann MC, Lenzlinger PM, Joller H, Trentz O, Kossmann T. IL-10 levels in cerebrospinal fluid and serum of patients with severe traumatic brain injury: relationship to IL-6, TNF-alpha, TGF-beta1 and blood-brain barrier function. J Neuroimmunol 1999; 101 (02) 211-221
• 10 Margulies S, Hicks R. ; Combination Therapies for Traumatic Brain Injury Workshop Leaders. Combination therapies for traumatic brain injury: prospective considerations. J Neurotrauma 2009; 26 (06) 925-939
• 11 Hughbanks-Wheaton DK, Birch DG, Fish GE. , et al. Safety assessment of docosahexaenoic acid in X-linked retinitis pigmentosa: the 4-year DHAX trial. Invest Ophthalmol Vis Sci 2014; 55 (08) 4958-4966
• 12 Salem Jr N, Vandal M, Calon F. The benefit of docosahexaenoic acid for the adult brain in aging and dementia. Prostaglandins Leukot Essent Fatty Acids 2015; 92: 15-22
• 13 Yurko-Mauro K, McCarthy D, Rom D. , et al; MIDAS Investigators. Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline. Alzheimers Dement 2010; 6 (06) 456-464
• 14 Mulder KA, King DJ, Innis SM. Omega-3 fatty acid deficiency in infants before birth identified using a randomized trial of maternal DHA supplementation in pregnancy. PLoS One 2014; 9 (01) e83764
• 15 Sinha RA, Khare P, Rai A. , et al. Anti-apoptotic role of omega-3-fatty acids in developing brain: perinatal hypothyroid rat cerebellum as apoptotic model. Int J Dev Neurosci 2009; 27 (04) 377-383
• 16 Chang CY, Kuan YH, Li JR. , et al. Docosahexaenoic acid reduces cellular inflammatory response following permanent focal cerebral ischemia in rats. J Nutr Biochem 2013; 24 (12) 2127-2137
• 17 Niu SL, Mitchell DC, Litman BJ. Optimization of receptor-G protein coupling by bilayer lipid composition II: formation of metarhodopsin II-transducin complex. J Biol Chem 2001; 276 (46) 42807-42811
• 18 Bailes JE, Mills JD. Docosahexaenoic acid reduces traumatic axonal injury in a rodent head injury model. J Neurotrauma 2010; 27 (09) 1617-1624
• 19 Begum G, Yan HQ, Li L, Singh A, Dixon CE, Sun D. Docosahexaenoic acid reduces ER stress and abnormal protein accumulation and improves neuronal function following traumatic brain injury. J Neurosci 2014; 34 (10) 3743-3755
• 20 Mills JD, Hadley K, Bailes JE. Dietary supplementation with the omega-3 fatty acid docosahexaenoic acid in traumatic brain injury. Neurosurgery 2011; 68 (02) 474-481 , discussion 481
• 21 Wu A, Ying Z, Gomez-Pinilla F. The salutary effects of DHA dietary supplementation on cognition, neuroplasticity, and membrane homeostasis after brain trauma. J Neurotrauma 2011; 28 (10) 2113-2122
• 22 Wu A, Ying Z, Gomez-Pinilla F. Exercise facilitates the action of dietary DHA on functional recovery after brain trauma. Neuroscience 2013; 248: 655-663
• 23 Stark KD, Van Elswyk ME, Higgins MR, Weatherford CA, Salem Jr N. Global survey of the omega-3 fatty acids, docosahexaenoic acid and eicosapentaenoic acid in the blood stream of healthy adults. Prog Lipid Res 2016; 63: 132-152
• 24 Bohnen N, Twijnstra A, Wijnen G, Jolles J. Tolerance for light and sound of patients with persistent post-concussional symptoms 6 months after mild head injury. J Neurol 1991; 238 (08) 443-446
• 25 Rathbone AT, Tharmaradinam S, Jiang S, Rathbone MP, Kumbhare DA. A review of the neuro- and systemic inflammatory responses in post concussion symptoms: Introduction of the “post-inflammatory brain syndrome” PIBS. Brain Behav Immun 2015; 46: 1-16
• 26 Sharp DJ, Jenkins PO. Concussion is confusing us all. Pract Neurol 2015; 15 (03) 172-186
• 27 McNamara KC, Lisembee AM, Lifshitz J. The whisker nuisance task identifies a late-onset, persistent sensory sensitivity in diffuse brain-injured rats. J Neurotrauma 2010; 27 (04) 695-706
• 28 Cao T, Thomas TC, Ziebell JM, Pauly JR, Lifshitz J. Morphological and genetic activation of microglia after diffuse traumatic brain injury in the rat. Neuroscience 2012; 225: 65-75
• 29 Lifshitz J. Fluid percussion injury model. In: Chen ZXJ, Xu X-M, Zhang J. , eds. Animal Models of Acute Neurological Injuries. Totowa, NJ: The Humana Press Inc; 2008: 369-384
• 30 Ziebell JM, Taylor SE, Cao T, Harrison JL, Lifshitz J. Rod microglia: elongation, alignment, and coupling to form trains across the somatosensory cortex after experimental diffuse brain injury. J Neuroinflammation 2012; 9: 247
• 31 Hosseini AH, Lifshitz J. Brain injury forces of moderate magnitude elicit the fencing response. Med Sci Sports Exerc 2009; 41 (09) 1687-1697
• 32 Guseva MV, Hopkins DM, Scheff SW, Pauly JR. Dietary choline supplementation improves behavioral, histological, and neurochemical outcomes in a rat model of traumatic brain injury. J Neurotrauma 2008; 25 (08) 975-983
• 33 Murai H, Pierce JE, Raghupathi R. , et al. Twofold overexpression of human beta-amyloid precursor proteins in transgenic mice does not affect the neuromotor, cognitive, or neurodegenerative sequelae following experimental brain injury. J Comp Neurol 1998; 392 (04) 428-438
• 34 Pleasant JM, Carlson SW, Mao H, Scheff SW, Yang KH, Saatman KE. Rate of neurodegeneration in the mouse controlled cortical impact model is influenced by impactor tip shape: implications for mechanistic and therapeutic studies. J Neurotrauma 2011; 28 (11) 2245-2262
• 35 Prins ML, Hovda DA. Mapping cerebral glucose metabolism during spatial learning: interactions of development and traumatic brain injury. J Neurotrauma 2001; 18 (01) 31-46
• 36 Rowe RK, Harrison JL, O'Hara BF, Lifshitz J. Recovery of neurological function despite immediate sleep disruption following diffuse brain injury in the mouse: clinical relevance to medically untreated concussion. Sleep 2014; 37 (04) 743-752
• 37 Smith DH, Nakamura M, McIntosh TK. , et al. Brain trauma induces massive hippocampal neuron death linked to a surge in beta-amyloid levels in mice overexpressing mutant amyloid precursor protein. Am J Pathol 1998; 153 (03) 1005-1010
• 38 Smith DH, Soares HD, Pierce JS. , et al. A model of parasagittal controlled cortical impact in the mouse: cognitive and histopathologic effects. J Neurotrauma 1995; 12 (02) 169-178
• 39 Learoyd AE, Lifshitz J. Comparison of rat sensory behavioral tasks to detect somatosensory morbidity after diffuse brain-injury. Behav Brain Res 2012; 226 (01) 197-204
• 40 Folch J, Lees M, Sloane Stanley GH. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 1957; 226 (01) 497-509
• 41 Little KY, McLaughlin DP, Zhang L. , et al. Brain dopamine transporter messenger RNA and binding sites in cocaine users: a postmortem study. Arch Gen Psychiatry 1998; 55 (09) 793-799
• 42 van Bregt DR, Thomas TC, Hinzman JM. , et al. Substantia nigra vulnerability after a single moderate diffuse brain injury in the rat. Exp Neurol 2012; 234 (01) 8-19
• 43 Weissman BA, Raveh L. Peripheral benzodiazepine receptors: on mice and human brain imaging. J Neurochem 2003; 84 (03) 432-437
• 44 Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates. 6th ed. Amsterdam, Boston: Academic Press/Elsevier; 2007
• 45 Arterburn LM, Hall EB, Oken H. Distribution, interconversion, and dose response of n-3 fatty acids in humans. Am J Clin Nutr 2006; 83 (6, Suppl) 1467S-1476S
• 46 Kelley BJ, Lifshitz J, Povlishock JT. Neuroinflammatory responses after experimental diffuse traumatic brain injury. J Neuropathol Exp Neurol 2007; 66 (11) 989-1001
• 47 Woodcock T, Morganti-Kossmann MC. The role of markers of inflammation in traumatic brain injury. Front Neurol 2013; 4: 18
• 48 Wu A, Ying Z, Gomez-Pinilla F. Dietary strategy to repair plasma membrane after brain trauma: implications for plasticity and cognition. Neurorehabil Neural Repair 2014; 28 (01) 75-84
• 49 Salem Jr N, Kim HY, Yergey JA. Docosahexaenoic acid: membrane function and metabolism. In: Simopoulos AP, Kifer RR, Martin R. , eds. The Health Effects of Polyunsaturated Fatty Acids in Seafoods. New York: Academic Press; 1986: 263-317
• 50 Hall JC, Priestley JV, Perry VH, Michael-Titus AT. Docosahexaenoic acid, but not eicosapentaenoic acid, reduces the early inflammatory response following compression spinal cord injury in the rat. J Neurochem 2012; 121 (05) 738-750
• 51 King VR, Huang WL, Dyall SC, Curran OE, Priestley JV, Michael-Titus AT. Omega-3 fatty acids improve recovery, whereas omega-6 fatty acids worsen outcome, after spinal cord injury in the adult rat. J Neurosci 2006; 26 (17) 4672-4680
• 52 Liu ZH, Yip PK, Adams L. , et al. A single bolus of docosahexaenoic acid promotes neuroplastic changes in the innervation of spinal cord interneurons and motor neurons and improves functional recovery after spinal cord injury. J Neurosci 2015; 35 (37) 12733-12752
• 53 Eady TN, Khoutorova L, Anzola DV. , et al. Acute treatment with docosahexaenoic acid complexed to albumin reduces injury after a permanent focal cerebral ischemia in rats. PLoS One 2013; 8 (10) e77237
• 54 Hong SH, Belayev L, Khoutorova L, Obenaus A, Bazan NG. Docosahexaenoic acid confers enduring neuroprotection in experimental stroke. J Neurol Sci 2014; 338 (1-2): 135-141
• 55 Hong SH, Khoutorova L, Bazan NG, Belayev L. Docosahexaenoic acid improves behavior and attenuates blood-brain barrier injury induced by focal cerebral ischemia in rats. Exp Transl Stroke Med 2015; 7 (01) 3
• 56 Moriguchi T, Harauma A, Salem Jr N. Plasticity of mouse brain docosahexaenoic acid: modulation by diet and age. Lipids 2013; 48 (04) 343-355
• 57 Huang WL, King VR, Curran OE. , et al. A combination of intravenous and dietary docosahexaenoic acid significantly improves outcome after spinal cord injury. Brain 2007; 130 (Pt 11): 3004-3019
• 58 Moriguchi T, Loewke J, Garrison M, Catalan JN, Salem Jr N. Reversal of docosahexaenoic acid deficiency in the rat brain, retina, liver, and serum. J Lipid Res 2001; 42 (03) 419-427
• 59 Moriguchi T, Salem Jr N. Recovery of brain docosahexaenoate leads to recovery of spatial task performance. J Neurochem 2003; 87 (02) 297-309
• 60 Igarashi M, DeMar Jr JC, Ma K, Chang L, Bell JM, Rapoport SI. Docosahexaenoic acid synthesis from alpha-linolenic acid by rat brain is unaffected by dietary n-3 PUFA deprivation. J Lipid Res 2007; 48 (05) 1150-1158
• 61 Gonzalez-Casanova I, Rzehak P, Stein AD. , et al. Maternal single nucleotide polymorphisms in the fatty acid desaturase 1 and 2 coding regions modify the impact of prenatal supplementation with DHA on birth weight. Am J Clin Nutr 2016; 103 (04) 1171-1178
• 62 Kothapalli KS, Ye K, Gadgil MS. , et al. Positive selection on a regulatory insertion-deletion polymorphism in FADS2 influences apparent endogenous synthesis of arachidonic acid. Mol Biol Evol 2016; 33 (07) 1726-1739
• 63 Steer CD, Lattka E, Koletzko B, Golding J, Hibbeln JR. Maternal fatty acids in pregnancy, FADS polymorphisms, and child intelligence quotient at 8 y of age. Am J Clin Nutr 2013; 98 (06) 1575-1582
• 64 DeGeorge JJ, Nariai T, Yamazaki S, Williams WM, Rapoport SI. Arecoline-stimulated brain incorporation of intravenously administered fatty acids in unanesthetized rats. J Neurochem 1991; 56 (01) 352-355
• 65 Ong WY, Farooqui T, Kokotos G, Farooqui AA. Synthetic and natural inhibitors of phospholipases A2: their importance for understanding and treatment of neurological disorders. ACS Chem Neurosci 2015; 6 (06) 814-831
• 66 Farias SE, Heidenreich KA, Wohlauer MV, Murphy RC, Moore EE. Lipid mediators in cerebral spinal fluid of traumatic brain injured patients. J Trauma 2011; 71 (05) 1211-1218
• 67 Vandal M, Alata W, Tremblay C. , et al. Reduction in DHA transport to the brain of mice expressing human APOE4 compared to APOE2. J Neurochem 2014; 129 (03) 516-526
• 68 Giza CC, Hovda DA. The neurometabolic cascade of concussion. J Athl Train 2001; 36 (03) 228-235
• 69 Sarkadi-Nagy E, Wijendran V, Diau GY. , et al. The influence of prematurity and long chain polyunsaturate supplementation in 4-week adjusted age baboon neonate brain and related tissues. Pediatr Res 2003; 54 (02) 244-252
• 70 Yagi S, Hara T, Ueno R. , et al. Serum concentration of eicosapentaenoic acid is associated with cognitive function in patients with coronary artery disease. Nutr J 2014; 13 (01) 112
• 71 Jeffrey BG, Weisinger HS, Neuringer M, Mitchell DC. The role of docosahexaenoic acid in retinal function. Lipids 2001; 36 (09) 859-871
• 72 Wijendran V, Lawrence P, Diau GY, Boehm G, Nathanielsz PW, Brenna JT. Significant utilization of dietary arachidonic acid is for brain adrenic acid in baboon neonates. J Lipid Res 2002; 43 (05) 762-767
• 73 Igarashi M, Chang L, Ma K, Rapoport SI. Kinetics of eicosapentaenoic acid in brain, heart and liver of conscious rats fed a high n-3 PUFA containing diet. Prostaglandins Leukot Essent Fatty Acids 2013; 89 (06) 403-412
• 74 Buckley CD, Gilroy DW, Serhan CN. Proresolving lipid mediators and mechanisms in the resolution of acute inflammation. Immunity 2014; 40 (03) 315-327
• 75 Harrison JL, Rowe RK, Ellis TW. , et al. Resolvins AT-D1 and E1 differentially impact functional outcome, post-traumatic sleep, and microglial activation following diffuse brain injury in the mouse. Brain Behav Immun 2015; 47: 131-140
• 76 Luo CL, Li QQ, Chen XP. , et al. Lipoxin A4 attenuates brain damage and downregulates the production of pro-inflammatory cytokines and phosphorylated mitogen-activated protein kinases in a mouse model of traumatic brain injury. Brain Res 2013; 1502: 1-10
• 77 Bazan NG, Eady TN, Khoutorova L. , et al. Novel aspirin-triggered neuroprotectin D1 attenuates cerebral ischemic injury after experimental stroke. Exp Neurol 2012; 236 (01) 122-130
• 78 Orr SK, Palumbo S, Bosetti F. , et al. Unesterified docosahexaenoic acid is protective in neuroinflammation. J Neurochem 2013; 127 (03) 378-393
• 79 Chen CT, Bazinet RP. β-oxidation and rapid metabolism, but not uptake regulate brain eicosapentaenoic acid levels. Prostaglandins Leukot Essent Fatty Acids 2015; 92: 33-40
• 80 Morganti-Kossmann MC, Rancan M, Stahel PF, Kossmann T. Inflammatory response in acute traumatic brain injury: a double-edged sword. Curr Opin Crit Care 2002; 8 (02) 101-105
• 81 Frugier T, Morganti-Kossmann MC, O'Reilly D, McLean CA. In situ detection of inflammatory mediators in post mortem human brain tissue after traumatic injury. J Neurotrauma 2010; 27 (03) 497-507
• 82 Morganti-Kossmann MC, Rancan M, Otto VI, Stahel PF, Kossmann T. Role of cerebral inflammation after traumatic brain injury: a revisited concept. Shock 2001; 16 (03) 165-177
• 83 Semple BD, Bye N, Rancan M, Ziebell JM, Morganti-Kossmann MC. Role of CCL2 (MCP-1) in traumatic brain injury (TBI): evidence from severe TBI patients and CCL2-/- mice. J Cereb Blood Flow Metab 2010; 30 (04) 769-782
• 84 Allan SM, Rothwell NJ. Cytokines and acute neurodegeneration. Nat Rev Neurosci 2001; 2 (10) 734-744
• 85 Khalfoun B, Thibault F, Watier H, Bardos P, Lebranchu Y. Docosahexaenoic and eicosapentaenoic acids inhibit in vitro human endothelial cell production of interleukin-6. Adv Exp Med Biol 1997; 400B: 589-597
• 86 De Caterina R, Cybulsky MI, Clinton SK, Gimbrone Jr MA, Libby P. The omega-3 fatty acid docosahexaenoate reduces cytokine-induced expression of proatherogenic and proinflammatory proteins in human endothelial cells. Arterioscler Thromb 1994; 14 (11) 1829-1836
• 87 Yaqoob P, Calder P. Effects of dietary lipid manipulation upon inflammatory mediator production by murine macrophages. Cell Immunol 1995; 163 (01) 120-128
• 88 Venneti S, Lopresti BJ, Wang G. , et al. PK11195 labels activated microglia in Alzheimer's disease and in vivo in a mouse model using PET. Neurobiol Aging 2009; 30 (08) 1217-1226
• 89 Hamm RJ, Lyeth BG, Jenkins LW, O'Dell DM, Pike BR. Selective cognitive impairment following traumatic brain injury in rats. Behav Brain Res 1993; 59 (1-2): 169-173
• 90 Lifshitz J, Kelley BJ, Povlishock JT. Perisomatic thalamic axotomy after diffuse traumatic brain injury is associated with atrophy rather than cell death. J Neuropathol Exp Neurol 2007; 66 (03) 218-229
• 91 Pu H, Guo Y, Zhang W. , et al. Omega-3 polyunsaturated fatty acid supplementation improves neurologic recovery and attenuates white matter injury after experimental traumatic brain injury. J Cereb Blood Flow Metab 2013; 33 (09) 1474-1484
• 92 Harrison JL, Rowe RK, O'Hara BF, Adelson PD, Lifshitz J. Acute over-the-counter pharmacological intervention does not adversely affect behavioral outcome following diffuse traumatic brain injury in the mouse. Exp Brain Res 2014; 232 (09) 2709-2719
• 93 Mayer CL, Huber BR, Peskind E. Traumatic brain injury, neuroinflammation, and post-traumatic headaches. Headache 2013; 53 (09) 1523-1530
• 94 Potts MB, Koh SE, Whetstone WD. , et al. Traumatic injury to the immature brain: inflammation, oxidative injury, and iron-mediated damage as potential therapeutic targets. NeuroRx 2006; 3 (02) 143-153
• 95 Cherry JD, Tripodis Y, Alvarez VE. , et al. Microglial neuroinflammation contributes to tau accumulation in chronic traumatic encephalopathy. Acta Neuropathol Commun 2016; 4 (01) 112
• 96 Johnson VE, Stewart JE, Begbie FD, Trojanowski JQ, Smith DH, Stewart W. Inflammation and white matter degeneration persist for years after a single traumatic brain injury. Brain 2013; 136 (Pt 1): 28-42
• 97 Kumar A, Rinwa P, Dhar H. Microglial inhibitory effect of ginseng ameliorates cognitive deficits and neuroinflammation following traumatic head injury in rats. Inflammopharmacology 2014; 22 (03) 155-167
• 98 Trépanier MO, Hopperton KE, Orr SK, Bazinet RP. N-3 polyunsaturated fatty acids in animal models with neuroinflammation: an update. Eur J Pharmacol 2016; 785: 187-206
• 99 Chen S, Zhang H, Pu H. , et al. n-3 PUFA supplementation benefits microglial responses to myelin pathology. Sci Rep 2014; 4: 7458
• 100 Hjorth E, Zhu M, Toro VC. , et al. Omega-3 fatty acids enhance phagocytosis of Alzheimer's disease-related amyloid-β42 by human microglia and decrease inflammatory markers. J Alzheimers Dis 2013; 35 (04) 697-713
• 101 Cherry JD, Olschowka JA, O'Banion MK. Neuroinflammation and M2 microglia: the good, the bad, and the inflamed. J Neuroinflammation 2014; 11: 98
• 102 Michael-Titus AT, Priestley JV. Omega-3 fatty acids and traumatic neurological injury: from neuroprotection to neuroplasticity?. Trends Neurosci 2014; 37 (01) 30-38
• 103 Desai A, Park T, Barnes J, Kevala K, Chen H, Kim HY. Reduced acute neuroinflammation and improved functional recovery after traumatic brain injury by α-linolenic acid supplementation in mice. J Neuroinflammation 2016; 13 (01) 253
• 104 Taishi P, Churchill L, De A, Obal Jr F, Krueger JM. Cytokine mRNA induction by interleukin-1beta or tumor necrosis factor alpha in vitro and in vivo. Brain Res 2008; 1226: 89-98
• 105 Zhang W, Li B, Guo Y. , et al. Rhamnetin attenuates cognitive deficit and inhibits hippocampal inflammatory response and oxidative stress in rats with traumatic brain injury. Cent Eur J Immunol 2015; 40 (01) 35-41
• 106 Wang K, Yuan CP, Wang W. , et al. Expression of interleukin 6 in brain and colon of rats with TNBS-induced colitis. World J Gastroenterol 2010; 16 (18) 2252-2259
• 107 Hovens IB, Schoemaker RG, van der Zee EA, Absalom AR, Heineman E, van Leeuwen BL. Postoperative cognitive dysfunction: Involvement of neuroinflammation and neuronal functioning. Brain Behav Immun 2014; 38: 202-210
• 108 Wei J, Wu F, He A. , et al. Microglia activation: one of the checkpoints in the CNS inflammation caused by Angiostrongylus cantonensis infection in rodent model. Parasitol Res 2015; 114 (09) 3247-3254
• 109 Neeb L, Hellen P, Hoffmann J, Dirnagl U, Reuter U. Methylprednisolone blocks interleukin 1 beta induced calcitonin gene related peptide release in trigeminal ganglia cells. J Headache Pain 2016; 17: 19
• 110 Kuzawińska O, Lis K, Cudna A, Bałkowiec-Iskra E. Gender differences in the neurochemical response of trigeminal ganglion neurons to peripheral inflammation in mice. Acta Neurobiol Exp (Warsz) 2014; 74 (02) 227-232
• 111 Marics B, Peitl B, Varga A. , et al. Diet-induced obesity alters dural CGRP release and potentiates TRPA1-mediated trigeminovascular responses. Cephalalgia 2017; 37 (06) 581-591
• 112 Bowen EJ, Schmidt TW, Firm CS, Russo AF, Durham PL. Tumor necrosis factor-alpha stimulation of calcitonin gene-related peptide expression and secretion from rat trigeminal ganglion neurons. J Neurochem 2006; 96 (01) 65-77
• 113 Rozen T, Swidan SZ. Elevation of CSF tumor necrosis factor alpha levels in new daily persistent headache and treatment refractory chronic migraine. Headache 2007; 47 (07) 1050-1055
• 114 Vause CV, Durham PL. Identification of cytokines and signaling proteins differentially regulated by sumatriptan/naproxen. Headache 2012; 52 (01) 80-89
• 115 Kontos AP, Elbin RJ, Lau B. , et al. Posttraumatic migraine as a predictor of recovery and cognitive impairment after sport-related concussion. Am J Sports Med 2013; 41 (07) 1497-1504
• 116 Lifshitz J, Lisembee AM. Neurodegeneration in the somatosensory cortex after experimental diffuse brain injury. Brain Struct Funct 2012; 217 (01) 49-61
• 117 Russell KL, Berman NE, Gregg PR, Levant B. Fish oil improves motor function, limits blood-brain barrier disruption, and reduces Mmp9 gene expression in a rat model of juvenile traumatic brain injury. Prostaglandins Leukot Essent Fatty Acids 2014; 90 (01) 5-11
• 118 Desai A, Kevala K, Kim HY. Depletion of brain docosahexaenoic acid impairs recovery from traumatic brain injury. PLoS One 2014; 9 (01) e86472
• 119 Schober ME, Requena DF, Abdullah OM. , et al. Dietary docosahexaenoic acid improves cognitive function, tissue sparing, and magnetic resonance imaging indices of edema and white matter injury in the immature rat after traumatic brain injury. J Neurotrauma 2016; 33 (04) 390-402
• 120 Dixon CE, Liu SJ, Jenkins LW. , et al. Time course of increased vulnerability of cholinergic neurotransmission following traumatic brain injury in the rat. Behav Brain Res 1995; 70 (02) 125-131
• 121 Zhang YP, Cai J, Shields LB, Liu N, Xu XM, Shields CB. Traumatic brain injury using mouse models. Transl Stroke Res 2014; 5 (04) 454-471
• 122 Oliver JM, Jones MT, Kirk KM. , et al. Effect of docosahexaenoic acid on a biomarker of head trauma in American football. Med Sci Sports Exerc 2016; 48 (06) 974-982