Abstract
Vigabatrin is the drug of choice in resistant epilepsy and infantile spasms. Ataxia, tremors, and abnormal gait have been frequently reported following its use indicating cerebellar involvement. This study aimed, for the first time, to investigate the involvement of necroptosis and apoptosis in the VG-induced cerebellar cell loss and the possible protective role of combined omega-3 and vitamin B12 supplementation. Fifty Sprague-Dawley adult male rats (160-200 g) were divided into equal five groups: the control group received normal saline, VG200 and VG400 groups received VG (200 mg or 400 mg/kg, respectively), VG200 + OB and VG400 + OB groups received combined VG (200 mg or 400 mg/kg, respectively), vitamin B12 (1 mg/kg), and omega-3 (1 g/kg). All medications were given daily by gavage for four weeks. Histopathological changes were examined in H&E and luxol fast blue (LFB) stained sections. Immunohistochemical staining for caspase-3 and receptor-interacting serine/threonine-protein kinase-1 (RIPK1) as well as quantitative real-time polymerase chain reaction (qRT-PCR) for myelin basic protein (MBP), caspase-3, and receptor-interacting serine/threonine-protein kinase-3 (RIPK3) genes were performed. VG caused a decrease in the granular layer thickness and Purkinje cell number, vacuolations, demyelination, suppression of MBP gene expression, and induction of caspases-3, RIPK1, and RIPK3 in a dose-related manner. Combined supplementation with B12 and omega-3 improved the cerebellar histology, increased MBP, and decreased apoptotic and necroptotic markers. In conclusion, VG-induced neuronal cell loss is dose-dependent and related to both apoptosis and necroptosis. This could either be ameliorated (in low-dose VG) or reduced (in high-dose VG) by combined supplementation with B12 and omega-3.
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Abbreviations
- ARPE19:
-
Adult retinal pigment- epithelial cell line-19
- BCL2:
-
B-cell lymphoma 2
- BDNF:
-
Brain-derived neurotrophic factor
- BSA:
-
Bovine serum albumin
- Caspases-3:
-
Cysteine-aspartic acid protease-3
- DAB:
-
Diaminobenzidine
- DHA:
-
Docosahexaenoic acid
- ER:
-
Endoplasmic reticulum
- GABA:
-
Gamma-aminobutyric acid
- GABAAR:
-
Cl − permeable GABAA receptor channels
- GABA-T:
-
GABA-transaminase
- HRP:
-
Horse radish peroxidase
- IL:
-
Interleukin
- KCC2:
-
K + -Cl − cotransporter 2.
- LFB:
-
Luxol fast blue stain
- MLKL:
-
Mixed lineage kinase domain like pseudokinase
- NKCC1:
-
Na + -K + -2Cl − cotransporter 1
- PUFA:
-
Polyunsaturated fatty acid
- qRT-PCR:
-
Quantitative real-time—polymerase chain reaction
- RIPK1:
-
Receptor-interacting serine/threonine-protein kinase 1
- RIPK3:
-
Receptor-interacting serine/threonine-protein kinase-3
- ROS:
-
Reactive oxygen species
- THP-1:
-
Human monocytic cell line
- TNF:
-
Tumor necrosis factor
- TNFR1:
-
Tumor necrosis factor receptor 1
- VGB:
-
Vigabatrin
References
Adhikari S, Sathian B, Koirala DP, Rao KS (2013) Profile of children admitted with seizures in a tertiary care hospital of Western Nepal. BMC Pediatr 27:13–43. https://doi.org/10.1186/1471-2431-13-43
Anitha P (2020) Approaches to Alleviate the Vigabatrin Induced Retinal Toxicity. Electronic Theses and Dissertations. https://egrove.olemiss.edu/etd/1842. Accessed on 12 October 2019
Bancroft JD, Gamble M (2002) Theory and practice of the histological techniques. In: Bancroft JD, Gamble M (eds) The Hematoxylin and Eosin, 5th edn. Churchill Livingstone, London, Chp.8, pp 125–139
Begum G, Yan HQ, Li L, Singh A, Dixon CE, Sun D (2014) Docosahexaenoic acid reduces ER stress and abnormal protein accumulation and improves neuronal function following traumatic brain injury. J Neurosci 5(10):3743–3755. https://doi.org/10.1523/JNEUROSCI.2872-13.2014 34 ) .
Belizario J, Vieira-Cordeiro L, Enns S (2015) Necroptotic cell death signaling and execution pathway: lessons from knockout mice. Mediat Inflamm 2015:128076. https://doi.org/10.1155/2015/128076
Ben-Menachem E (2011) Mechanism of action of vigabatrin: correcting misperceptions. Acta Neurol Scand 124:5–15. https://doi.org/10.1111/j.1600-0404.2011.01596.x
Bhat R, Axtella R, Mitrab A, Mirandaa M, Locka C, Tsienb RW et al (2010) Inhibitory role for GABA in autoimmune inflammation. PNAS 107(6):2580–2585. https://doi.org/10.1073/pnas.0915139107
Boscia F, Begum G, Pignataro G, Sirabella R, Cuomo O, Casamassa A et al (2016) Glial Na(+) -dependent ion transporters in pathophysiological conditions. Glia 64(10):1677–1697. https://doi.org/10.1002/glia.23030. DOI
Calderon-Ospina CA, Nava‐Mesa MO (2020) B Vitamins in the nervous system: Current knowledge of the biochemical modes of action and synergies of thiamine, pyridoxine, and cobalamin. CNS Neurosci Ther 26:5–13. https://doi.org/10.1111/cns.13207
Carmant L (2011) Vigabatrin therapy for infantile spasms: review of major trials in Europe, Canada, and the United States; and recommendations for dosing. Acta Neurol Scand Suppl 192:36–47. https://doi.org/10.1111/j.1600-0404.2011.01599.x
Chan K, Hoon M, Pattnaik BR, Ver Hoeve JN, Wahlgren B, Gloe S et al (2020) Vigabatrin Induced Retinal Functional Alterations and Second-Order Neuron Plasticity in C57BL/6J Mice. Invest Ophthalmol Vis Sci 7(2):17. https://doi.org/10.1167/iovs.61.2.17 61 ) .
Chen X, Li W, Ren J, Huang D, He WT, Song Y et al (2014) Translocation of mixed lineage kinase domain-like protein to plasma membrane leads to necrotic cell death. Cell Res 24:105–121. https://doi.org/10.1038/cr.2013.171
Chen X, Pan Z, Fang Z, Lin W, Wu S, Yang F et al (2018) Omega-3 polyunsaturated fatty acid attenuates traumatic brain injury-induced neuronal apoptosis by inducing autophagy through the upregulation of SIRT1-mediated deacetylation of Beclin-1. J Neuroinflammation 15(1):310. https://doi.org/10.1186/s12974-018-1345-8
Chen X, Wu S, Chen C, Xie B, Fang Z, Hu W et al (2017) Omega-3 polyunsaturated fatty acid supplementation attenuates microglial-induced inflammation by inhibiting the HMGB1/TLR4/NF-κB pathway following experimental traumatic brain injury. J Neuroinflammation 24(1):143. https://doi.org/10.1186/s12974-018-1151-3 14 ) .
Choi ME, Price DR, Ryter SW, Choi AMK (2019) Necroptosis: A crucial pathogenic mediator of human disease. JCI Insight 4(15):e128834. https://doi.org/10.1172/jci.insight.128834
de Almagro MC, Vucic D (2015) Necroptosis: pathway diversity and characteristics. Semin Cell Dev Biol 39:56–62. https://doi.org/10.1016/j.semcdb.2015.02.002
de Queiroz KB, Cavalcante-Silva V, Lopes FL, Rocha GA, D’Almeida V, Coimbra RS (2020) Vitamin B12 is neuroprotective in experimental pneumococcal meningitis through modulation of hippocampal DNA methylation. J Neuroinflammation 17(1):96. https://doi.org/10.1186/s12974-020-01763-y
Degterev A, Huang Z, Boyce M, Li Y, Jagtap P, Mizushima N et al (2005) Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat Chem Biol 1:112–119. https://doi.org/10.1038/nchembio711
Farías JG, Carrasco-Pozo C, Carrasco Loza R, Sepúlveda N, Álvarez P, Quezada M et al (2017) Polyunsaturated fatty acid induces cardioprotection against ischemia-reperfusion through the inhibition of NF-kappaB and induction of Nrf2. Exp Biol Med 242(10):1104–1114. https://doi.org/10.1177/1535370216649263
Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P et al (2018) Molecular mechanisms of cell death: Recommendations of the Nomenclature Committee on Cell Death. Cell Death Differ 25:486–541. https://doi.org/10.1038/s41418-017-0012-4
Gemelli T, de Andrade RB, Rojas DB, Zanatta A, Schirmbeck GH, Funcha C et al (2018) Chronic Exposure to β-Alanine Generates Oxidative Stress and Alters Energy Metabolism in Cerebral Cortex and Cerebellum of Wistar Rats. Mol Neurobiol 55:5101–5110. https://doi.org/10.1007/s12035-017-0711-3
Gómez-Meda BC, Zamora-Perez AL, Muñoz-Magallanes T, Sánchez-Parada MG, García Bañuelos JJ, Guerrero-Velázquez C et al (2016) Nuclear abnormalities in buccal mucosa cells of patients with type I and II diabetes treated with folic acid. Mutat Res Genet Toxicol Environ Mutagen 797:1–8. https://doi.org/10.1016/j.mrgentox.2015.12.003
Gröber U, Kisters K, Schmidt J (2013) Neuroenhancement with vitamin B12—underestimated neurological significance. Nutrients 5(12):5031–5045. https://doi.org/10.3390/nu5125031
Halliwell B (2001) Role of free radicals in the neurodegenerative diseases: therapeutic implications for antioxidant treatment. Drugs Aging 8(9):685–716. https://doi.org/10.2165/00002512-200118090-00004
Harvey LD, Yin Y, Attarwala IY, Begum G, Deng J, Yan HQ et al (2015) Administration of DHA Reduces Endoplasmic Reticulum Stress-Associated Inflammation and Alters Microglial or Macrophage Activation in Traumatic Brain Injury. ASN neuro 18(6):1759091415618969. https://doi.org/10.1177/1759091415618969 7 ) .
Heckmann BL, Tummers B, Green DR (2019) Crashing the computer: apoptosis vs. necroptosis in neuroinflammation. Cell Death Differ 26:41–52. https://doi.org/10.1038/s41418-018-0195-3
Hernández-Benítez R, Sedeño-Cortés A, Ramos-Mandujano G, Pasantes-Morales H (2014) Regulatory volume decrease in neural precursor cells: taurine efflux and gene microarray analysis. Cell Physiol Biochem 34(6):2038–2048. https://doi.org/10.1159/000366399
Huang G, Xue J, Sun X, Wang J, Yu LL (2018) Necroptosis in 3-chloro-1, 2-propanediol (3-MCPD)-dipalmitate-induced acute kidney injury in vivo and its repression by miR-223-3p. Toxicology 406–407:33–43. https://doi.org/10.1016/j.tox.2018.05.015
Huang TL, Wen YT, Ho YC, Wang JK, Lin KH, Tsai RK (2020) Algae Oil Treatment Protects Retinal Ganglion Cells (RGCs) via ERK Signaling Pathway in Experimental Optic Nerve Ischemia. Mar Drugs 27(2):83. https://doi.org/10.3390/md18020083 18 ) .
Jakaria M, Azam S, Haque ME, Jo SH, Uddin MS, Kim IS et al (2019) Taurine and its analogs in neurological disorders: Focus on therapeutic potential and molecular mechanisms. Redox Biol 24:101223. https://doi.org/10.1016/j.redox.2019.101223
Jammoul F, Wang Q, Nabbout R, Coriat C, Duboc A, Simonutti M et al (2009) Taurine deficiency is a cause of vigabatrin-induced retinal phototoxicity. Ann Neurol 65(1):98–107. https://doi.org/10.1002/ana.21526
Jantzie LL, Hu MY, Park HK, Jackson MC, Yu J, Maxwell JR, Jensen FE (2015) Chloride cotransporter NKCC1 inhibitor bumetanide protects against white matter injury in a rodent model of periventricular leukomalacia. Pediatr Res 77(4):554–562. https://doi.org/10.1038/pr.2015.9
Jong CJ, Ito T, Prentice H, Wu JY, Schaffer SW (2017) Role of mitochondria and endoplasmic reticulum in taurine-deficiency-mediated apoptosis. Nutrients 9(8):795. https://doi.org/10.3390/nu9080795
Kishino A, Hayashi K, Maeda M, Jike T, Hidai C, Nomura Y, Oshima T (2019) Caspase-8 Regulates Endoplasmic Reticulum Stress-Induced Necroptosis Independent of the Apoptosis Pathway in Auditory Cells. Int J Mol Sci 20(23):5896. https://doi.org/10.3390/ijms20235896
Lee KH, Kang TB (2019) The molecular links between cell death and inflammasome. Cells 8:1057–1079. https://doi.org/10.3390/cells8091057
Linnebank M, Moskau S, Semmler A, Widman G, Stoffel-Wagner B, Weller M (2011) Antiepileptic drugs interact with folate and vitamin B12 serum levels. Ann Neurol 69(2):352–359. https://doi.org/10.1002/ana.22229
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25(4):402–408. https://doi.org/10.1006/meth.2001.1262
Mohamed EA, Kassem HH (2018) Protective effect of nebivolol on doxorubicin-induced cardiotoxicity in rats. Arch Med Sci 14(6):1450–1458. https://doi.org/10.5114/aoms.2018.79008
Moosavirad SA, Rabbani M, Sharifzadeh M, Hosseini-Sharifabad A (2016) Protective Effect of Vitamin C, Vitamin B12 and omega-3 on Lead-Induced Memory Impairment in Rat. Res Pharm Sci 11(5):390–396. https://doi.org/10.4103/1735-5362.192490
Nair AB, Jacob SA (2016) Simple practice guide for dose conversion between animals and human. J Basic Clin Pharma 7:27–31. https://doi.org/10.4103/0976-0105.177703
Nelson GR (2015) Management of infantile spasms. Transl Pediatr 4(4):260–270. https://doi.org/10.3978/j.issn.2224-4336.2015.09.01
Niu X, Zheng S, Liu H, Li S (2018) Protective effects of taurine against inflammation, apoptosis, and oxidative stress in brain injury. Mol Med Rep 18(5):4516–4522. https://doi.org/10.3892/mmr.2018.9465
Okada K, Tanaka H, Temporin K, Okamoto M, Kuroda Y, Moritomo H et al (2010) Methylcobalamin increases Erk1/2 and Akt activities through the methylation cycle and promotes nerve regeneration in a rat sciatic nerve injury model. Exp Neurol 222:191–203. https://doi.org/10.1016/j.expneurol.2009.12.017
Pacheco FJ, Almaguel FG, Evans W, Rios-Colon L, Filippov V, Leoh LS et al (2014) Docosahexanoic acid antagonizes TNF-alpha-induced necroptosis by attenuating oxidative stress, ceramide production, lysosomal dysfunction, and autophagic features. Inflamm Res 63:859–871. https://doi.org/10.1007/s00011-014-0760-2
Padmanabhan S, Waly MI, Taranikanti V, Guizani N, Ali A, Rahman MS et al (2019) Folate/Vitamin B12 Supplementation Combats Oxidative Stress-Associated Carcinogenesis in a Rat Model of Colon Cancer. Nutr Cancer 71(1):100–110. https://doi.org/10.1080/01635581.2018.1513047
Parviz M, Vogel K, Gibson KM, Pearl PL (2014) Disorders of GABA metabolism: SSADH and GABA-transaminase deficiencies. J Pediatr Epilepsy 25(4):217–227. https://doi.org/10.3233/PEP-14097 3 ) .
Preece NE, Houseman J, King MD, Weller RO, Williams SR (2004) Development of vigabatrin induced lesions in the rat brain studied by magnetic resonance imaging, histology, and immunocytochemistry. Synapse 53(1):36–43. https://doi.org/10.1002/syn.20038
Pu H, Guo Y, Zhang W, Huang L, Wang G, Liou AK et al (2013) Omega-3 polyunsaturated fatty acid supplementation improves neurologic recovery and attenuates white matter injury after experimental traumatic brain injury. J Cereb Blood Flow Metab 33(9):1474–1484. https://doi.org/10.1038/jcbfm.2013.108
Qiao M, Malisza KL, Del Bigio MR, Kozlowski P, Seshia SS, Tuor UI (2000) Effect of Long-Term Vigabatrin Administration on the Immature Rat Brain. Epilepsia 41(6):655–665. https://doi.org/10.1111/j.1528-1157.2000.tb00225.x
Rathod R, Khaire A, Kemse N, Kale A, Joshi S (2014) Maternal omega-3 fatty acid supplementation on vitamin B12 rich diet improves brain omega-3 fatty acids, neurotrophins and cognition in the Wistar rat offspring. Brain Dev 36(10):853–863. https://doi.org/10.1016/j.braindev.2013.12.007
Rodrigues C, Chiron C, Ounissi M, Dulac O, Gaillard S, Nabbout R et al (2019) Pharmacokinetic evaluation of vigabatrin dose for the treatment of refractory focal seizures in children using adult and pediatric data. Epilepsy Res 150:38–45. https://doi.org/10.1016/j.eplepsyres.2019.01.002
Sable P, Dangat K, Kale A, Joshi S (2011) Altered brain neurotrophins at birth: consequence of imbalance in maternal folic acid and vitamin B12 metabolism. Neuroscience 8:190:127–134. https://doi.org/10.1016/j.neuroscience.2011.05.010
Scalabrino G, Buccellato FR, Veber D, Mutti E (2003) New basis of the neurotrophic action of vitamin B12. Clin Chem Lab Med 41(11):1435–1437. https://doi.org/10.1515/CCLM.2003.220
Schlanger S, Shinitzky M, Yam D (2002) Diet Enriched with Omega-3 Fatty Acids Alleviates Convulsion Symptoms in Epilepsy Patients. Epilepsia 43(1):103–104. https://doi.org/10.1046/j.1528-1157.2002.13601.x
Schonstedt V, Stecher X, Venegas V, Silva C (2015) Vigabatrin-induced MRI changes associated with extrapyramidal symptoms in a child with infantile spasms. Neuroradiol J 28(5):515–518. https://doi.org/10.1177/1971400915598082
Singh D, Dubey A, Jethani SL (2013) Vigabatrin induced Cell loss in the Cerebellar Cortex of Albino Rats. J Clin Diagn Res 7(11):2555–2558. https://doi.org/10.7860/JCDR/2013/6187.3610
Singh D, Jethani SL, Dubey A (2014) Vigabatrin induced intramyelinic oedema in cerebellum of albino rats. Journal of the anatomical society of India 63:156–160. https://doi.org/10.1016/j.jasi.2014.11.008
Singh D, Dubey A, Jethani SL (2018) Vigabatrin toxicity-effects on optic nerve. Journal of the Anatomical Society of India 67:158–161. https://doi.org/10.1016/j.jasi.2018.09.001
Sommerfeld A, Reinehr R, Häussinger D (2015) Tauroursodeoxycholate Protects Rat Hepatocytes from Bile AcidInduced Apoptosis via β1-Integrin- and Protein Kinase A-Dependent Mechanisms. Cell Physiol Biochem 36:866–883. https://doi.org/10.1159/000430262
Sun GY, Simonyi A, Fritsche KL, Chuang DY, Hannink M, Gu Z et al (2018) Docosahexaenoic acid (DHA): an essential nutrient and a nutraceutical for brain health and diseases. Prostaglandins Leukot Essent Fatty Acids 136:3–13. https://doi.org/10.1016/j.plefa.2017.03.006
Tan A, Sullenbarger B, Prakash R, Mc Daniel JC (2018) Supplementation with eicosapentaenoic acid and docosahexaenoic acid reduces high levels of circulating proinflammatory cytokines in aging adults: a randomized, controlled study. Prostaglandins Leukot Essent Fatty Acids 136:3–13. https://doi.org/10.1016/j.plefa.2018.03.010
Tao Y, Yang J, Ma Z, Yan Z, Liu C, Ma J et al (2016) The Vigabatrin Induced Retinal Toxicity is associated with Photopic Exposure and Taurine Deficiency: An in Vivo Study. Cell Physiol Biochem 40:831–846. https://doi.org/10.1159/000453143
Tillman L, Zhang J (2019) Crossing the Chloride Channel: The Current and Potential Therapeutic Value of the Neuronal K+-Cl- Cotransporter KCC2. Biomed Res Int 21;2019:8941046. https://doi.org/10.1155/2019/8941046
Tomi M, Tajima A, Tachikawa M, Hosoya K (2008) Function of taurine transporter (Slc6a6/TauT) as a GABA transporting protein and its relevance to GABA transport in rat retinal capillary endothelial cells. Biochim Biophys Acta 1778:2138–2142. https://doi.org/10.1016/j.bbamem.2008.04.012
Tummers B, Green DR (2017) Caspase-8: regulating life and death. Immunol Rev 277(1):76–89. https://doi.org/10.1111/imr.12541
Vargas RA (2018) The GABAergic System: An Overview of Physiology, Physiopathology and Therapeutics. Int J Clin Pharmacol Pharmacother 3:142. https://doi.org/10.15344/2456-3501/2018/142
Vinogradova LV, Kuznetsova GD, Shatskova AB, van Rijn CM (2005) Vigabatrin in low doses selectively suppresses the clonic component of audiogenically kindled seizures in rats. Epilepsia 46(6):800–810. https://doi.org/10.1111/j.1528-1167.2005.52604.x
Vogel KR, Ainslie GR, Schmidt MA, Wisor JP, Gibson KM (2017) mTOR inhibition mitigates molecular and biochemical alterations of vigabatrin-induced visual field toxicity in mice. Pediatr Neurol 66:44–52.e1. https://doi.org/10.1016/j.pediatrneurol.2016.09.016
Vogel KR, Pearl PL, Theodore WH, McCarter RC, Jakobs C, Gibson KM (2013) Thirty years beyond discovery–clinical trials in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism. J Inherit Metab Dis 36:401–410. https://doi.org/10.1007/s10545-012-9499-5
Walters DC, Jansen E, Ainslie GR, Salomons GS, Brown MN, Schmidt MA et al (2019) Preclinical tissue distribution and metabolic correlations of vigabatrin, an antiepileptic drug associated with potential use-limiting visual field defects. Pharmacol Res Perspect 7(1):e00456. https://doi.org/10.1002/prp2.456 7 ) .
Wang J, Shi Y, Zhang L, Zhang F, Hu X, Zhang W et al (2014) Omega-3 polyunsaturated fatty acids enhance cerebral angiogenesis and provide long-term protection after stroke. Neurobiol Dis 68:91–103. https://doi.org/10.1016/j.nbd.2014.04.014
Wu F, Xu K, Liu L, Zhang K, Xia L, Zhang M et al (2019) Vitamin B12 Enhances Nerve Repair and Improves Functional Recovery After Traumatic Brain Injury by Inhibiting ER Stress-Induced Neuron Injury. Front Pharmacol 10:406. https://doi.org/10.3389/fphar.2019.00406
Tao Y, Yang J, Ma Z, Yan Z, Liu C, Ma J, Wang Y, Yang Z, Huang YF (2016) The Vigabatrin Induced Retinal Toxicity is Associated with Photopic Exposure and Taurine Deficiency: An In Vivo Study. Cell Physiol Biochem 40(5):831–846. https://doi.org/10.1159/000453143
Yu Y, Fu P, Yu Z, Xie M, Wang W, Luo X (2018) NKCC1 inhibition attenuates chronic cerebral hypoperfusion-induced white matter lesions by enhancing progenitor cells of oligodendrocyte proliferation. J Mol Neurosci 64(3):449–458. https://doi.org/10.1007/s12031-018-1043-0
Yuan S, Lia H, Yanga C, Xiea W, Wanga Y, Zhanga J et al (2020) DHA attenuates Aβ-induced necroptosis through the RIPK1/RIPK3 signaling pathway in THP-1 monocytes. Biomed Pharmacother 126:110102. https://doi.org/10.1016/j.biopha.2020.110102
Yuan J, Amin P, Ofengeim D (2019) Necroptosis and RIPK1-mediated neuroinflammation in CNS diseases. Nat Rev Neurosci 20:19–33. https://doi.org/10.1038/s41583-018-0093-1
Zhang S, Tang MB, Luo HY, Shi CH, Xu YM (2017) Necroptosis in neurodegenerative diseases: A potential therapeutic target. Cell Death Dis 8:e2905. https://doi.org/10.1038/cddis.2017.286
Zhang X, Matsuda M, Yaegashi N, Nabe T, Kitatani K (2020) Regulation of Necroptosis by Phospholipids and Sphingolipids. Cells 9(3):627. https://doi.org/10.3390/cells9030627
Zhou J, Zhuang J, Li J, Ooi E, Bloom J, Poon C et al (2013) Long-term post-stroke changes include myelin loss, specific deficits in sensory and motor behaviors and complex cognitive impairment detected using active place avoidance. PLoS One 8(3):e57503. https://doi.org/10.1371/journal.pone.0057503
Zhu W, Ding Y, Kong W, Li T, Chen H (2018) Docosahexaenoic Acid (DHA) Provides Neuroprotection in Traumatic Brain Injury Models via Activating Nrf2-ARE Signaling. Inflammation 41(4):1182–1193. https://doi.org/10.1007/s10753-018-0765-z
Zirpoli H, Chang CL, Carpentier YA, Michael-Titus AT, Ten VS, Deckelbaum RJ (2020) Novel Approaches for Omega-3 Fatty Acid Therapeutics:Chronic Versus Acute Administration to Protect Heart, Brain, and Spinal Cord. Annu Rev Nutr 40:161–187. https://doi.org/10.1146/annurev-nutr-082018-124539
Acknowledgements
The authors would like to express their gratitude to the anatomy and biochemistry departments, Mansoura University, Egypt and to King Khalid University, Saudi Arabia, for providing administrative and technical support.
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The authors would like to extend their appreciation to the Deanship of Scientific Research at King Khalid University for funding this project through the research group program under grant number (R.G.P. 2/31/40).
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Abd El-kader, M., Hamza, E., El-Gamal, R. et al. Modulation of vigabatrin induced cerebellar injury: the role of caspase-3 and RIPK1/RIPK3-regulated cell death pathways. J Mol Histol 52, 781–798 (2021). https://doi.org/10.1007/s10735-021-09984-y
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DOI: https://doi.org/10.1007/s10735-021-09984-y