Skip to main content
SpringerLink
Log in

Nigrostriatal damage after systemic rotenone and/or lipopolysaccharide and the effect of cannabis

  • Original Article
  • Published:
Comparative Clinical Pathology Aims and scope Submit manuscript

Abstract

In this study, we compared the effects of systemic rotenone, lipopolysaccharide (LPS), or both rotenone and LPS on oxidative stress and nigrostriatal cell damage in mice. We further investigated the therapeutic potential of cannabis in these rodent models of Parkinson's disease. Rotenone (1.5 mg/kg, subcutaneously, three times per week), LPS (0.2 mg/kg, intraperitoneally, daily), or LPS plus rotenone was given alone or in combination with cannabis (20 mg/kg, expressed as Δ9-tetrahydrocannabinol, subcutaneously daily) for 2 weeks. Mice were tested for behavioral changes on the 14th day after different treatments. Biochemical markers of oxidative stress such as malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (nitrite), paraoxonase 1 (PON1) activity as well as monoamine neurotransmitters in the brain were determined. Histopathology, tyrosine hydroxylase immunoreactivity (TH-ir), inducible nitric oxide synthase (iNOS), and caspase-3 immunohistochemistry were also performed. Either rotenone or LPS injection was followed by increased MDA and decreased GSH in the cortex, striatum, and the rest of the brain (subcortex). There was increased nitrite and decreased PON1 activity in the cortex and subcortex. The increase in nitrite by combined LPS–rotenone in the cortex was significantly higher than that caused only LPS. In the subcortex, nitrite was significantly increased compared with either agent alone. The biochemical changes induced by rotenone, LPS, or rotenone + LPS were reduced, but not prevented by cannabis. In the striatum, the administration of only cannabis induced mild degenerative changes with shrunken neurons and pyknotic nuclei, a slight decrease in TH-ir, and mild iNOS and caspase-3 immunoreactivities. LPS injection was followed by pyknotic and apoptotic nuclei and perinuclear cytoplasmic vacuoles and decreased TH-ir with mild iNOS and caspase-3 immunoreactivities. Meanwhile, marked striatal neurodegeneration was observed after rotenone with shrunken and distorted neurons, pericellular haloes, inflammation, and hemorrhage. Markedly decreased TH-ir and increased iNOS and caspase-3 immunoreactivities were observed. The loss of pigmented neurons, the decrease of TH-ir, and the increase in both iNOS and caspase-3 immunoreactivities were markedly increased by administering both rotenone and LPS. The administration of cannabis did not reduce nigrostriatal damage due to rotenone, LPS, or rotenone + LPS, although an improvement in striatal TH-ir was observed. Thus, (1) systemic rotenone or LPS increased oxidative and nitrosative stress in brain and (2) induced nigrostriatal neuronal damage; (3) the effect was not limited to the striatum but involved other areas such as the cerebral cortex and hippocampus; (4) the neuronal damage caused by rotenone was increased in the presence of systemic inflammation; (5) rotenone induced caspase-3-mediated apoptosis; (6) cannabis reduced brain oxidative stress but failed to alleviate nigrostriatal damage due to rotenone, LPS, or rotenone + LPS; and (7) cannabis increased TH immnunostaining in the striatum after rotenone, LPS, or rotenone + LPS. This effect of cannabis does not appear to reflect a neuroprotective effect and might be due to increased striatal dopamine levels by cannabis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Abdel-Salam OME, El-Shamarka ME-S, Salem NA, Gaafar AE-DM (2012) Effects of Cannabis sativa extract on haloperidol-induced catalepsy and oxidative stress in the mice. EXCLI J 11:45–58

    Google Scholar 

  • Abdel-Salam OME, El-Shamarka ME-S, Shaffee N, Gaafar AE-DM (2013) Study of the effect of Cannabis sativa on liver and brain damage caused by thioacetamide. Comp Clin Pathol. doi:10.1007/s00580-012-1641-0

    Google Scholar 

  • Alam M, Schmidt WJ (2002) Rotenone destroys dopaminergic neurons and induces parkinsonian symptoms in rats. Behav Brain Res 136:317–324

    Article  PubMed  CAS  Google Scholar 

  • Alam ZI, Daniel SE, Lees AJ, Marsden DC, Jenner P, Halliwell B (1997) A generalised increase in protein carbonyls in the brain in Parkinson's but not incidental Lewy body disease. J Neurochem 69:1326–1329

    Article  PubMed  CAS  Google Scholar 

  • Ashton CH (2001) Pharmacology and effects of cannabis: a brief review. Br J Psychiatr 178:101–106

    Article  CAS  Google Scholar 

  • Baird AL, Meldrum A, Dunnett SB (2001) The staircase test of skilled reaching in mice. Brain Res Bull 54:243–250

    Article  PubMed  CAS  Google Scholar 

  • Berardelli A, Rothwell JC, Thompson PD, Hallett M (2001) Pathophysiology of bradykinesia in Parkinson's disease. Brain 124:2131–2146

    Article  PubMed  CAS  Google Scholar 

  • Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT (2000) Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat Neurosci 3:1301–1306

    Article  PubMed  CAS  Google Scholar 

  • Brenneisen R (2006) Chemistry and analysis of phytocannabinoids and other cannabis constituents. In: ElSohly MA (ed) Forensic science and medicine: marijuana and the cannabinoids. Humana, Totowa, pp 17–49

    Google Scholar 

  • Brown TP, Rumsby PC, Capleton AC, Rushton L, Levy LS (2006) Pesticides and Parkinson's disease—is there a link? Environ Health Perspect 114:156–164

    Article  PubMed  PubMed Central  Google Scholar 

  • Buttini M, Mir A, Appel K, Wiederhold KH, Limonta S, Gebicke-Haerter PJ, Boddeke HW (1997) Lipopolysaccharide induces expression of tumour necrosis factor alpha in rat brain: inhibition by methylprednisolone and by rolipram. Br J Pharmacol 122:1483–1489

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Cao C, Matsumura K, Yamagata K, Watanabe Y (1995) Induction by lipopolysaccharide of cyclooxygenase-2 mRNA in rat brain; its possible role in the febrile response. Brain Res 697:187–196

    Article  PubMed  CAS  Google Scholar 

  • Capasso R, Borrelli F, Aviello G, Romano B, Scalisi C, Capasso F, Izzo AA (2008) Cannabidiol, extracted from Cannabis sativa, selectively inhibits inflammatory hypermotility in mice. Br J Pharmacol 154:1001–1008

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Carroll CB, Bain PG, Teare L, Liu X, Joint C, Wroath C, Parkin SG, Fox P, Wright D, Hobart J, Zajicek JP (2004) Cannabis for dyskinesia in Parkinson disease. A randomized double-blind crossover study. Neurology 63:1245–1250

    Article  PubMed  CAS  Google Scholar 

  • Costello S, Cockburn M, Bronstein J, Zhang X, Ritz B (2009) Parkinson's disease and residential exposure to maneb and paraquat from agricultural applications in the central valley of California. Am J Epidemiol 169:919–926

    Article  PubMed  PubMed Central  Google Scholar 

  • Crawley JN (2007) What’s wrong with my mouse? Behavioral phenotyping of transgenic and knockout mice, Second editionth edn. Wiley, Hoboken

    Book  Google Scholar 

  • Di Monte DA (2003) The environment and Parkinson's disease: is the nigrostriatal system preferentially targeted by neurotoxins? Lancet Neurol 2:531–538

    Article  PubMed  Google Scholar 

  • Drechsel DA, Patel M (2008) Role of reactive oxygen species in the neurotoxicity of environmental agents implicated in Parkinson's disease. Free Radic Biol Med 44:1873–1886

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem 82:70–77

    Article  PubMed  CAS  Google Scholar 

  • Feng Y, Liang ZH, Wang T, Qiao X, Liu HJ, Sun SG (2006) alpha-Synuclein redistributed and aggregated in rotenone-induced Parkinson's disease rats. Neurosci Bull 22:288–293

    PubMed  CAS  Google Scholar 

  • Ferrari CC, Tarelli R (2011) Parkinson's disease and systemic inflammation. Parkinsons Dis 2011:436813

    PubMed  PubMed Central  Google Scholar 

  • Fiorucci S, Mencarelli A, Meneguzzi A, Lechi A, Morelli A, del Soldato P, Minuz P (2002) NCX-4016 (NO-Aspirin) inhibits lipopolysaccharide-induced tissue factor expression in vivo. Role of nitric oxide. Circulation 106:3120–3125

    Article  PubMed  Google Scholar 

  • Fiz J, Durán M, Capellà D, Carbonell J, Farré M (2011) Cannabis use in patients with fibromyalgia: effect on symptoms relief and health-related quality of life. PLoS One 6:e18440

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Furlong CE (2008) Paraoxonases: an historical perspective. In: Mackness B, Mackness M, Aviram M, Paragh G (eds) The paraoxonases: their role in disease development and xenobiotic metabolism. Springer, Dordrecht, pp 3–31

    Google Scholar 

  • Gao HM, Liu B, Zhang W, Hong JS (2003a) Novel anti-inflammatory therapy for Parkinson's disease. Trends Pharmacol Sci 24:395–401

    Article  PubMed  CAS  Google Scholar 

  • Gao HM, Hong JS, Zhang W, Liu B (2003b) Synergistic dopaminergic neurotoxicity of the pesticide rotenone and inflammogen lipopolysaccharide: relevance to the etiology of Parkinson's disease. J Neurosci 23:1228–1236

    PubMed  CAS  Google Scholar 

  • Graybiel AM (2000) The basal ganglia. Curr Biol 10:R509–R511

    Article  PubMed  CAS  Google Scholar 

  • Halliwell B (2001) Role of free radicals in the neurodegenerative diseases: therapeutic implications for antioxidant treatment. Drugs Aging 18:685–716

    Article  PubMed  CAS  Google Scholar 

  • Halliwell B, Gutteridge JM (1989). Free radicals in biology and medicine, 2nd ed. Oxford: Clarendon Press, pp. 22–85

  • Hampson AJ, Grimaldi M, Lolic M, Wink D, Rosenthal R, Axelrod J (2000) Neuroprotective antioxidants from marijuana. Ann N Y Acad Sci 899:274–282

    Article  PubMed  CAS  Google Scholar 

  • Higashino K, Takahashi Y, Yamamura Y (1972) Release of phenyl acetate esterase from liver microsomes by carbon tetrachloride. Clin Chim Acta 41:313–320

    Article  PubMed  CAS  Google Scholar 

  • Hirsch EC (1994) Biochemistry of Parkinson's disease with special reference to the dopaminergic systems. Mol Neurobiol 9:135–142

    Article  PubMed  CAS  Google Scholar 

  • Hirsch EC, Hunot S (2009) Neuroinflammation in Parkinson's disease: a target for neuroprotection? Lancet Neurol 8:382–397

    Article  PubMed  CAS  Google Scholar 

  • Howard J, Anie KA, Holdcroft A, Korn S, Davies SC (2005) Cannabis use in sickle cell disease: a questionnaire study. Br J Haematol 131:123–128

    Article  PubMed  Google Scholar 

  • Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55:181–184

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Jacewicz M, Czapski GA, Katkowska I, Strosznajder RP (2009) Systemic administration of lipopolysaccharide impairs glutathione redox state and object recognition in male mice. The effect of PARP-1 inhibitor. Folia Neuropathol 47:321–328

    PubMed  CAS  Google Scholar 

  • Jamroz-Wisniewska A, Beltowski J, Stelmasiak Z, Bartosik-Psujek H (2009) Paraoxonase 1 activity in different types of multiple sclerosis. MultScler 15:399–402

    CAS  Google Scholar 

  • Jeon P, Yang S, Jeong H, Kim H (2011) Cannabinoid receptor agonist protects cultured dopaminergic neurons from the death by the proteasomal dysfunction. Anat Cell Biol 44:135–142

    Article  PubMed  PubMed Central  Google Scholar 

  • Jeong HK, Jou I, Joe EH (2010) Systemic LPS administration induces brain inflammation but not dopaminergic neuronal death in the substantia nigra. Exp Mol Med 42:823–832

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Koprich JB, Reske-Nielsen C, Mithal P, Isacson O (2008) Neuroinflammation mediated by IL-1beta increases susceptibility of dopamine neurons to degeneration in an animal model of Parkinson's disease. J Neuroinflammation 5:8

    Article  PubMed  PubMed Central  Google Scholar 

  • Kumar KR, Djarmati-Westenberger A, Grünewald A (2011) Genetics of Parkinson’s disease. Semin Neurol 31:433–440

    Google Scholar 

  • La Du BN (1992) Human serum paraoxonase/arylesterase. In: Kalow W (ed) Pharmacogenetics of drug metabolism. Pergamon, New York, pp 51–91

    Google Scholar 

  • Lastres-Becker I, Molina-Holgado F, Ramos JA, Mechoulam R, Fernández-Ruiz J (2005) Cannabinoids provide neuroprotection against 6-hydroxydopamine toxicity in vivo and in vitro: relevance to Parkinson’s disease. Neurobiol Dis 19:96–107

    Google Scholar 

  • Layé S, Gheusi G, Cremona S, Combe C, Kelley K, Dantzer R, Parnet P (2000) Endogenous brain IL-1 mediates LPS-induced anorexia and hypothalamic cytokine expression. Am J Physiol Regul Integr Comp Physiol 279:R93–R98

    PubMed  Google Scholar 

  • Liu C, Walker JM (2006) Effects of a cannabinoid agonist on spinal nociceptive neurons in a rodent model of neuropathic pain. J Neurophysiol 96:2984–2994

    Google Scholar 

  • Luo C, Rajput AH, Akhtar S, Rajput A (2007) Alpha-synuclein and tyrosine hydroxylase expression in acute rotenone toxicity. Int J Mol Med 19:517–521

    PubMed  CAS  Google Scholar 

  • Meister A, Anderson ME (1983) Glutathione. Annu Rev Biochem 52:711–760

  • McGeer PL, Schwab C, Parent A, Doudet D (2003) Presence of reactive microglia in monkey substantia nigra years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration. Ann Neurol 54:599–604

    Article  PubMed  CAS  Google Scholar 

  • Moshage H, Kok B, Huizenga JR (1995) Nitrite and nitrate determination in plasma: a critical evaluation. Clin Chem 41:892–896

    PubMed  CAS  Google Scholar 

  • Müller-Vahl KR, Kolbe H, Schneider U, Emrich HM (1999) Cannabis in movement disorders. Forsch Komplementarmed 6(Suppl 3):23–27

    Article  PubMed  Google Scholar 

  • Noble F, Rubira E, Boulanouar M, Palmier B, Plotkine M, Warnet JM, Marchand-Leroux C, Massicot F (2007) Acute systemic inflammation induces central mitochondrial damage and amnesic deficit in adult Swiss mice. Neurosci Lett 424:106–110

    Article  PubMed  CAS  Google Scholar 

  • Pankratz N, Foroud T (2007) Genetics of Parkinson disease. Genet Med 9:801–811

    Article  PubMed  Google Scholar 

  • Pertwee RG, Ross RA (2002) Cannabinoid receptors and their ligands. Prostaglandins Leukot Essent Fatty Acids 66:101–121

    Article  PubMed  CAS  Google Scholar 

  • Pertwee RG (2005) Pharmacological actions of cannabinoids. Handb Exp Pharmacol 168:1–51

    Article  PubMed  CAS  Google Scholar 

  • Pertwee RG (2008) The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol 153:199–215

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Qian L, Flood PM (2008) Microglial cells and Parkinson's disease. Immunol Res 41:155–164

    Article  PubMed  CAS  Google Scholar 

  • Qin L, Wu X, Block ML, Liu Y, Breese GR, Hong JS, Knapp DJ, Crews FT (2007) Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia 55:453–462

    Article  PubMed  PubMed Central  Google Scholar 

  • Quan N, Whiteside M, Herkenham M (1998) Cyclooxygenase 2 mRNA expression in rat brain after peripheral injection of lipopolysaccharide. Brain Res 802:189–197

    Article  PubMed  CAS  Google Scholar 

  • Raetz CR, Whitfield C (2002) Lipopolysaccharide endotoxin. Annu Rev Biochem 71:635–700

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Reinarman C, Nunberg H, Lanthier F, Heddleston T (2011) Who are medical marijuana patients? Population characteristics from nine California assessment clinics. J Psychoactive Drugs 43:128–135

    Article  PubMed  Google Scholar 

  • Rodrigo L, Hernández AF, López-Caballero JJ, Gil F, Pla A (2001) Immunohistochemical evidence for the expression and induction of paraoxonase in rat liver, kidney, lung and brain tissue. Implications for its physiological role. Chem Biol Interact 137:123–137

    Article  PubMed  CAS  Google Scholar 

  • Rogers DC, Campbell CA, Stretton JL, Mackay KB (1997) Correlation between motor impairment and infarct volume after permanent and transient middle cerebral artery occlusion in the rat. Stroke 28:2060–2065

    Article  PubMed  CAS  Google Scholar 

  • Ruiz-Larrea MB, Leal AM, Liza M, Lacort M, de Groot H (1994) Antioxidant effects of estradiol and 2-hydroxyestradiol on iron-induced lipid peroxidation of rat liver microsomes. Steroids 59:383–388

    Article  PubMed  CAS  Google Scholar 

  • Santens P, Boon P, Van Roost D, Caemaert J (2003) The pathophysiology of motor symptoms in Parkinson's disease. Acta Neurol Belg 103:129–134

    PubMed  CAS  Google Scholar 

  • Sastre-Garriga J, Vila C, Clissold S, Montalban X (2011) THC and CBD oromucosal spray (Sativex A®) in the management of spasticity associated with multiple sclerosis. Expert Rev Neurother 11:627–637

    Article  PubMed  CAS  Google Scholar 

  • Schaar KL, Brenneman MM, Savitz SI (2010) Functional assessments in the rodent stroke model. Exp Transl Stroke Med 2:13

    Article  PubMed  PubMed Central  Google Scholar 

  • Seamon MJ, Fass JA, Maniscalco-Feichtl M, Abu-Shraie NA (2007) Medical marijuana and the developing role of the pharmacist. Am J Health Syst Pharm 64:1037–1044

    Article  PubMed  CAS  Google Scholar 

  • Sherer TB, Kim JH, Betarbet R, Greenamyre JT (2003) Subcutaneous rotenone exposure causes highly selective dopaminergic degeneration and alpha-synuclein aggregation. Exp Neurol 179:9–16

    Article  PubMed  CAS  Google Scholar 

  • Sian J, Dexter DT, Lees AJ, Daniel S, Agid Y, Javoy-Agid F, Jenner P, Marsden CD (1994) Alterations in glutathione levels in Parkinson's disease and other neurodegenerative disorders affecting basal ganglia. Ann Neurol 36:348–355

    Article  PubMed  CAS  Google Scholar 

  • Sies H (1991) Oxidative stress: introduction. In: Sies H (ed) Oxidative stress: oxidants and antioxidants. Academic, London

    Google Scholar 

  • Spencer SJ, Mouihate A, Pittman QJ (2007) Peripheral inflammation exacerbates damage after global ischemia independently of temperature and acute brain inflammation. Stroke 38:1570–1577

    Article  PubMed  CAS  Google Scholar 

  • Turner JC, Mahlberg PG (1984) Separation of acid and neutral cannabinoids in Cannabis sativa L. using HPLC. In: Agurell S, Dewey WL, Willete RE (eds) Chemical, pharmacological and therapeutic agents. Academic, London, pp 79–88

    Google Scholar 

  • Turrin NP, Gayle D, Ilyin SE, Flynn MC, Langhans W, Schwartz GJ, Plata-Salamán CR (2001) Pro-inflammatory and anti-inflammatory cytokine mRNA induction in the periphery and brain following intraperitoneal administration of bacterial lipopolysaccharide. Brain Res Bull 54:443–453

    Article  PubMed  CAS  Google Scholar 

  • van Vliet SA, Vanwersch RA, Jongsma MJ, Olivier B, Philippens IH (2008) Therapeutic effects of Delta 9-THC and modafinil in a marmoset Parkinson model. Eur Neuropsy-chopharmacol 18:383–389

    Article  Google Scholar 

  • Venderová K, Růzicka E, Vorísek V, Visnovský P (2004) Survey on cannabis use in Parkinson's disease: subjective improvement of motor symptoms. Mov Disord 19:1102–1106

    Article  PubMed  Google Scholar 

  • Wang AL, Yu AC, Lau LT, Lee C, le Wu M, Zhu X, Tso MO (2005) Minocycline inhibits LPS-induced retinal microglia activation. Neurochem Int 47:152–158

    Article  PubMed  CAS  Google Scholar 

  • Wang X, Quinn PJ (2010) Endotoxins: lipopolysaccharides of gram-negative bacteria. Subcell Biochem 53:3–25

    Article  PubMed  CAS  Google Scholar 

  • Watson AD, Berliner JA, Hama SY, La Du BN, Faull KF, Fogelman AM, Navab M (1995) Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein. J Clin Invest 96:2882–2891

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Ware MA, Adams H, Guy GW (2005) The medicinal use of cannabis in the UK: results of a nationwide survey. Int J Clin Pract 59:291–295

    Article  PubMed  CAS  Google Scholar 

  • Ware MA, Fitzcharles MA, Joseph L, Shir Y (2010) The effects of nabilone on sleep in fibromyalgia: results of a randomized controlled trial. Anesth Analg 110:604–610

    Article  PubMed  CAS  Google Scholar 

  • Wehr H, Bednarska-Makaruk M, Graban A, Lipczyńska-Łojkowska W, Rodo M, Bochyńska A, Ryglewicz D (2009) Paraoxonase activity and dementia. J NeurolSci 283:107–108

    CAS  Google Scholar 

  • Wei T, Chen C, Hou J, Xin W, Mori A (2000) Nitric oxide induces oxidative stress and apoptosis in neuronal cells. Biochim Biophys Acta 1498:72–79

    Google Scholar 

  • Wilsey B, Marcotte T, Tsodikov A, Millman J, Bentley H, Gouaux B, Fishman S (2008) A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. J Pain 9:506–521

    Article  PubMed  CAS  Google Scholar 

  • Yoritaka A, Hattori N, Uchida K, Tanaka M, Stadtman ER, Mizuno Y (1996) Immunohistochemical detection of 4-hydroxynonenal protein adducts in Parkinson disease. Proc Natl Acad Sci USA 1996(93):2696–2701

    Article  Google Scholar 

  • Zhang J, Perry G, Smith MA, Robertson D, Olson SJ, Graham DG, Montine TJ (1999) Parkinson's disease is associated with oxidative damage to cytoplasmic DNA and RNA in substantia nigra neurons. Am J Pathol 154:1423–1429

    Article  PubMed  CAS  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Toxicology and Narcotics, National Research Centre, Tahrir St., Dokki, Cairo, Egypt

    Omar M. E. Abdel-Salam & Marawa El-Sayed El-Shamarka

  2. Department of Pathology, National Research Centre, Cairo, Egypt

    Enayat A. Omara

  3. Department of Medical Biochemistry, National Research Centre, Cairo, Egypt

    Jihan Seid Hussein

Authors
  1. Omar M. E. Abdel-Salam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Enayat A. Omara
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marawa El-Sayed El-Shamarka
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jihan Seid Hussein
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Omar M. E. Abdel-Salam.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Abdel-Salam, O.M.E., Omara, E.A., El-Shamarka, M.ES. et al. Nigrostriatal damage after systemic rotenone and/or lipopolysaccharide and the effect of cannabis. Comp Clin Pathol 23, 1343–1358 (2014). https://doi.org/10.1007/s00580-013-1788-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00580-013-1788-3

Keywords

Search

Navigation