Skip to main content

Advertisement

Log in

Relationship between inflammatory reaction and ischemic injury of caudate-putamen in rats: inflammatory reaction and brain ischemia

  • Original Article
  • Published:
Anatomical Science International Aims and scope Submit manuscript

Abstract

Inflammatory response after middle cerebral artery occlusion (MCAO) has been a focus of research recently, but the effect of inflammatory cells on ischemic neurons remains unclear. In order to study the effect of the inflammatory reaction on brain ischemic injury, we observed the morphology, number and distribution of CD3-, CD8-, ED1- and ED2-positive cells systematically in the caudate-putamen of rats in a MCAO model. The present results show that all four types of inflammatory cells first infiltrated the ischemic penumbra and then migrated into the center of the ischemic area, but the morphological changes and infiltration processes differed significantly; the infiltration of CD3- and CD8-positive cells into the ischemic area started at 3 days postischemia, and their number peaked at 1 week; however, although ED1- and ED2-positive cells were also observed at 3 days after ischemia, they reached their maximum number at 2 and 4 weeks, respectively. Moreover, ED1-and ED2-positive cells showed evident hyperplasia and hypertrophy in morphology. Our results also showed that the response of CD3-, CD8-, ED1- and ED2-positive cells in the ischemic area and the pathological changes in ischemic brain tissue could be inhibited by cyclosporine A. The results suggest that the infiltration and reaction of inflammatory cells are involved in the pathological process of ischemic brain injury.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  • Barone FC, Feuerstein GZ (1999) Inflammatory mediators and stroke: new opportunities for novel therapeutics. J Cereb Blood Flow Metab 19:819–834

    Article  PubMed  CAS  Google Scholar 

  • Barone FC, Hillegass LM, Price WJ et al (1991) Polymorphonuclear leukocyte infiltration into cerebral focal ischemic tissue: myeloperoxidase activity assay and histologic verification. J Neurosci Res 29:336–345

    Article  PubMed  CAS  Google Scholar 

  • Barone FC, Arvin B, Whit RF (1997) Tumor necrosis factor-alpha. A mediator of focal ischemic brain injury. Stroke 28:1233–1244

    PubMed  CAS  Google Scholar 

  • Bederson JB, Pitts LH, Nishimura MC, Davis RL, Bartkowski HM (1986) Evaluation of 2,3,5-triphenyltetrazolium chloride as a stain for detection and quantify cation of experimental cerebral infarction in rats. Stroke 17:1304–1308

    PubMed  CAS  Google Scholar 

  • Beninger RJ, Ranaldi R (1993) Microinjections of flupenthixol into the caudate-putamen but not the nucleus accumbens, amygdala or frontal cortex of rats produce intra-session decline food-reward operant responding. Behav Brain Res 55:203

    Article  PubMed  CAS  Google Scholar 

  • Benjelloun N, Renolleau S, Represa A (1999) Inflammatory responses in the cerebral cortex after ischemia in the P7 neonatal rat. Stroke 30:1916

    PubMed  CAS  Google Scholar 

  • Beray-Berthat V, Croci N, Plotkine M (2003) Polymorphonuclear neutrophils contribute to infarction and oxidative stress in the cortex but not in the caudate-putamen after ischemia–reperfusion in rats. Brain Res 987:32–38

    Article  PubMed  CAS  Google Scholar 

  • Brea D, Sobrino T, Ramos-Cabrer P (2009) Inflammatory and neuroimmunomodulatory changes in acute cerebral ischemia. Cerebrovasc Dis 27(Suppl 1):48–64

    Article  PubMed  CAS  Google Scholar 

  • Bruce AJ, Boling W, Kindy MS et al (1996) Altered neuronal and microglial responses to excitotoxic and ischemic brain injury in mice lacking TNF receptors. Nature Med 2:788–794

    Article  PubMed  CAS  Google Scholar 

  • Carlson NG, Wiegge WA, Chen J (1999) Inflammatory cytokines IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha impart neuroprotection to an excitotoxin through distinct pathways. J Immunol 163:3963–3968

    PubMed  CAS  Google Scholar 

  • Clark RK, Lee EV, White RF, Jonak ZL, Feuerstein GZ, Barone FC (1994) Reperfusion following focal stroke hastens inflammation and resolution of ischemic injured tissue. Brain Res Bull 35:387–392

    Article  PubMed  CAS  Google Scholar 

  • Connolly ES, Winfree CJ, Springer TA, Gutierrez-Ramos JC, Pinsky DJ et al (1996) Cerebral protection in homozygous null ICAM-1 mice after middle cerebral artery occlusion: role of neutrophil adhesion in the pathogenesis of stroke. J Clin Invest 97:209–216

    Article  PubMed  CAS  Google Scholar 

  • Członkowska A, Cyrta B, Korlak J (1979) Immunological observations on patients with acute cerebral vascular disease. J Neurol Sci 43(3):455–464

    Article  PubMed  Google Scholar 

  • Deng H, Han HS, Cheng D (2003) Mild hypothermia inhibits inflammation after experimental stroke and brain inflammation. Stroke 34:2495–2501

    Article  PubMed  Google Scholar 

  • Dirnagl U, Iadecola C, Moskowitz MA (1999) Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci 22:391–397

    Article  PubMed  CAS  Google Scholar 

  • Donnan GA, Fisher M, Macleod M, Davis SM (2008) Stroke. Lancet 371:1612–1623

    Article  PubMed  CAS  Google Scholar 

  • Eliasson MJL, Huang Z, RJl Ferrante (1999) Neuronal nitric oxide synthase activation and peroxynitrite formation in ischemic stroke linked to neural damage. J Neurosci 19:5910–5918

    PubMed  CAS  Google Scholar 

  • Fallon JT (1979) Simplified method for histochemical demonstration of experimental myocardial infarct. Circulation 60(Suppl 2):11–42

    Google Scholar 

  • Finsen BR, Jorgensen MB, Diemer NH, Jimmer J (1994) Microglial MHC antigen expression after ischemic and kainic acid lesions of the adult rat hippocampus. Glia 7:41–49

    Article  Google Scholar 

  • Fontaine V, Mohand-Said S, Hanoteau N (2002) Neurodegenerative and neuroprotective effects of tumor necrosis factor (TNF) in retinal ischemia: opposite roles of TNF receptor 1 and TNF receptor 2. J Neurosci 22:216

    Google Scholar 

  • Furlan M, Marchal G, Viader F (1996) Spontaneous neurological recovery after stroke the fate of the ischemic penumbra. Ann Neurol 40:216–226

    Article  PubMed  CAS  Google Scholar 

  • Garcia JH, Yoshida Y, Chen H (1993) Progression from ischemic injury to infarct following middle cerebral artery occlusion in the rat. Am J Pathol 142:623–635

    PubMed  CAS  Google Scholar 

  • Garcia JH, Liu KF, Yoshida Y, Lian J, Chen S, Del Zoppo GJ (1994) Influx of leukocytes and platelets in an evolving brain infarct (Wistar rat). Am J Pathol 144:188–199

    PubMed  CAS  Google Scholar 

  • Gidaay JM, Gasche YG, Copin JC (2005) Leukocyte-derived matrix metalloproteinase-9 mediates blood–brain barrier breakdown and is proinflammatory after transient focal cerebral ischemia. Am J Physiol Heart Circ Physiol 289:H558–H568

    Article  Google Scholar 

  • Giulian D (1987) Ameboid microglia as effectors of inflammation in the central nervous system. J Neurosci Res 18:155–171

    Article  PubMed  CAS  Google Scholar 

  • Giulian D, Baker TJ, Shih LN, Lachman LB (1986) Interleukin-1 of the central nervous system is produced by ameboid microglia. J Exp Med 164:594–604

    Article  PubMed  CAS  Google Scholar 

  • Giulian D, Woodward J, Young DG, Krebs JF, Lachman LB (1988) Interleukin-1 injection into mammalian brain stimulates astrogliosis and neovascularization. J Neurosci 8:2485–2490

    PubMed  CAS  Google Scholar 

  • Giulian D, Chen J, Ingeman JE (1989) The role of mononuclear phagocytes in wound healing after traumatic injury to adult mammalian brain. J Neurosci 9:4416–4429

    PubMed  CAS  Google Scholar 

  • Graeber MB, Streit WJ, Kreutzberg GW (1989) Identify of ED2-positive perivascular cells in rat brain. J Neuosci Res 22:103–106

    Article  CAS  Google Scholar 

  • Ivacko JA, Sun R, Silverstein FS (1996) Hypoxic–ischemia injury induces an acute microglial reaction in perinatal rats. Pediatr Res 39(1):39–47

    Article  PubMed  CAS  Google Scholar 

  • Jorgensen MB, Finsen BR, Jensen MB (1993) Microglial and astroglial reactions to ischemic and kainic acid-induced lesions of the adult rat hippocampus. Exp Neurol 120:70–88

    Article  PubMed  CAS  Google Scholar 

  • Kato H, Kogure K, Araki T, Itoyama Y (1995) Graded expression of immunomolecules on activated microglia in the hippocampus following ischemia in a rat model of ischemic tolerance. Brain Res 694:85–93

    Article  PubMed  CAS  Google Scholar 

  • Kato H, Kogure K, Liu XH (1996) Progressive expression of immunomolecules on activated-microglia and invading leukocytes following focal cerebral ischemia in the rat. Brain Res 734:203–212

    Article  PubMed  CAS  Google Scholar 

  • Kriz J (2006) Inflammation in ischemic brain injury: timing is important. Crit Rev Neurobiol 18:145–157

    PubMed  CAS  Google Scholar 

  • Kriz J, Lalancette-Hébert M (2009) Inflammation, plasticity and real-time imaging after cerebral ischemia. Acta Neuropathol 117(5):497–509

    Article  PubMed  CAS  Google Scholar 

  • Lalancette-Hebert M, Gowing G, Simard A, Weng YC, Kriz J (2007) Selective ablation of proliferating microglial cells exacerbates ischemic injury in the brain. J Neurosci 27:2596–2605

    Article  PubMed  CAS  Google Scholar 

  • Lieberman AP, Pitha PM, Shin HS, Shin ML (1989) Production of tumor necrosis factor and other cytokines by astrocytes stimulated with lipopolysaccharide or a neurotropic virus. Proc Natl Acad Sci USA 86:6348–6352

    Article  PubMed  CAS  Google Scholar 

  • Liesz A, Suri-Payer E, Veltkamp C (2009) Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke. Nat Med 15(2):192–199

    Article  PubMed  CAS  Google Scholar 

  • Liu Y, Jacobowitz DM, Barone F (1994) Quantitation of perivascular monocytes and macrophages around cerebral blood vessels of hypertensive and aged rats. J Cereb Blood Flow Metab 14:348–352

    Article  PubMed  CAS  Google Scholar 

  • Lo EH, Dalkara T, Moskowitz MA (2003) Mechanisms, challenges and opportunities in stroke. Nat Rev Neurosci 4:399–415

    Article  PubMed  CAS  Google Scholar 

  • Loddick SA, Rothwell NJ (1996) Neuroprotective effects of human recombinant interleukin-1 receptor antagonist in focal cerebral ischaemia in the rat. J Cereb Blood Flow Metab 16:932–940

    Article  PubMed  CAS  Google Scholar 

  • Marchal G, Beaudouin V, Rioux P (1996) Prolonged persistance of substantial volumes of potentially viable brain tissue after stroke: a correlative PET-CT study with voxel-based data analysis. Stroke 27:599–606

    PubMed  CAS  Google Scholar 

  • Matsuo Y, Onodera H, Shiga Y, Nakamura M, Kihara T, Kogure K (1994) Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemic brain injury in the rat. Effect of neutrophil depletion. Stroke 25:1469–1475

    PubMed  CAS  Google Scholar 

  • Matsuo Y, Kihara T, Ikeda M, Ninomiya M, Onodera H, Kogure K (1995) Role of neutrophils in radical production during ischemia and reperfusion of the rat brain: effect of neutrophil depletion on extracellular ascorbyl radical formation. J Cereb Blood Flow Metab 15:941–947

    Article  PubMed  CAS  Google Scholar 

  • McGeorge AJ, Faull RLM (1989) The organization of the projection from the cerebral cortex to the striatum in the rat. Neuroscience 29:503–537

    Article  PubMed  CAS  Google Scholar 

  • Morika T, Kalehua AN, Streit WJ (1991) The microglial reaction in the rat dorsal hippocampus following transient forebrain ischemia. J Cereb Blood Flow Metab 11:966–973

    Article  Google Scholar 

  • Patel PM, Drummond JC, Sano T (1993) Effect of ibuprofen on regional eicosanoid production and neuronal injury after forebrain ischemia in rats. Brain Res 614:315–324

    Article  PubMed  CAS  Google Scholar 

  • Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates, 4th edn. Academic, New York

    Google Scholar 

  • Pozzilli C, Lenzi GL, Argentino C (1985) Peripheral white blood cell count in cerebral ischemic infarction. Acta Neurol Scand 71(5):396–400

    Article  PubMed  CAS  Google Scholar 

  • Reichmann G, Schroeter M, Jander S (2002) Dendritic cells and dendritic-like microglia in focal cortical ischemia of the mouse brain. J Neuroimmunol 129:125–132

    Article  PubMed  CAS  Google Scholar 

  • Relton JK, Martin D, Thompson RC, Russell DA (1996) Peripheral administration of interleukin-1 receptor antagonist inhibits brain damage after focal cerebral ischemia in the rat. Exp Neurol 138:206–213

    Article  PubMed  CAS  Google Scholar 

  • Rieke GK, Cannon (1985) A histochemical study of cerebral cortical vessels and ganglionic vessels of the caudatoputamen in aging normotensive rats. Stroke 16(2):285

    PubMed  CAS  Google Scholar 

  • Sawada M, Kondo N, Suzumura A, Marunouchi T (1989) Production of tumor necrosis factor-alpha by microglia and astrocytes in culture. Brain Res 491:394–397

    Article  PubMed  CAS  Google Scholar 

  • Scherbel U, Raghupathi R, Nakamura M (1999) Differential acute and chronic responses of tumor necrosis factor-deficient mice to experimental brain injury. Proc Natl Acad Sci USA 96:8721–8726

    Article  PubMed  CAS  Google Scholar 

  • Shiga Y, Onodera H, Matsuo Y, Kogure K (1992) Cyclosporin A protects against ischemia–reperfusion injury in the brain. Brain Res 595:145–148

    Article  PubMed  CAS  Google Scholar 

  • Shu SY, Bao XM, Li Sx (1995) The afferent connections and its immunohistochemical characteristics of the marginal decision in rat corpus striatum. J Med Coll PLA 10:1

    Google Scholar 

  • Siesjö BK, Siesjö P (1996) Mechanisms of secondary brain injury. Eur J Anaesthesiol 13(3):247

    Article  PubMed  Google Scholar 

  • Stahel PF, Shohami E, Younis FM (2000) Experimental closed head injury: analysis of neurological outcome, blood–brain barrier dysfunction, intracranial neutrophil infiltration, and neuronal cell death in mice deficient in genes for pro-inflammatory cytokines. J Cereb Blood Flow Metab 20:369–380

    Article  PubMed  CAS  Google Scholar 

  • Stoll G, Jander S, Schroeter M (1998) Inflammation and glial responses in ischemic brain lesions. Prog Neurobiol 56(2):149–171

    Article  PubMed  CAS  Google Scholar 

  • Streit WJ, Graeber MB, Kreutzberg GW (1988) Functional plasticity of microglia: a review. Glia 1:301–307

    Article  PubMed  CAS  Google Scholar 

  • Sugimoto K, Iadecola C (2003) Delayed effect of administration of COX-2 inhibitor in mice with acute cerebral ischemia. Brain Res 960:273–276

    Article  PubMed  CAS  Google Scholar 

  • Swanson RA, Morton MT, Wu GT (1990) A semi-automated method for measuring brain infarct volume. J Cereb Blood Flow Metab 10(2):290

    Article  PubMed  CAS  Google Scholar 

  • Tamura A, Graham DI, McCulloch J (1981) Focal cerebral ischemia in the rat. 1. Description of technique and early neuropathological consequences following middle cerebral artery occlusion. J Cereb Blood Flow Metab 1(1):53

    Article  PubMed  CAS  Google Scholar 

  • Thomas WE (1992) Brain macrophages: evaluation of microglia and their functions. Brain Res Rev 17:61–74

    Article  PubMed  CAS  Google Scholar 

  • Thonnard-Neumann E (1972) Monocytes and basophilic granulocytes in the cranial circulation of patients with organic brain disorders. Stroke 3(3):286–299

    PubMed  CAS  Google Scholar 

  • Uchino H, Elmer E, Vchino K (1995) Cyclosporin A dramatically ameliorates CA1 hippocampal damage following transient forebrain ischaemia in the rat. Acta Physiol Scand 155(3):469

    Article  PubMed  CAS  Google Scholar 

  • Wang GJ, Deng HY, Maier GM (2002) Mild hypothermia reduces ICAM-1 expression, neutrophil infiltration and microglia/monocyte accumulation following experimental stroke. Neuroscience 114:1081–1090

    PubMed  CAS  Google Scholar 

  • Yamasaki Y, Matsuura N, Shozuhara H (1995) Interleukin-1 as a pathogenetic mediator of ischemic brain damage in rats. Stroke 26:676–680

    PubMed  CAS  Google Scholar 

  • Yenari MA, Kunis D, Sun GH (1998) Hu23F2G, an antibody recognizing the leukocyte CD11/CD18 integrin, reduces injury in a rabbit model of transient focal cerebral ischemia. Exp Neurol 153:223–233

    Article  PubMed  CAS  Google Scholar 

  • Zoli M, Grimaldi R, Ferrari R (1997) Short- and long-term changes in striatal neurones and astroglia after transient forebrain ischemia in rats. Stroke 28:1049–1058

    PubMed  CAS  Google Scholar 

Download references

Acknowledgment

This research was supported by the National Science Foundations of China (No. 30570572 and 30770679).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Wanlong Lei.

Additional information

S. Mu and L. Ouyang contributed equally to this article.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mu, S., Ouyang, L., Liu, B. et al. Relationship between inflammatory reaction and ischemic injury of caudate-putamen in rats: inflammatory reaction and brain ischemia. Anat Sci Int 86, 86–97 (2011). https://doi.org/10.1007/s12565-010-0091-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12565-010-0091-5

Keywords

Navigation