Top

Journal of Neuroinflammation

Published in:

Open Access 01-12-2021 | Stroke | Research

Differential effects of the cell cycle inhibitor, olomoucine, on functional recovery and on responses of peri-infarct microglia and astrocytes following photothrombotic stroke in rats

Authors: Wai Ping Yew, Natalia D. Djukic, Jaya S. P. Jayaseelan, Richard J. Woodman, Hakan Muyderman, Neil R. Sims

Published in: Journal of Neuroinflammation | Issue 1/2021

Abstract

Background

Following stroke, changes in neuronal connectivity in tissue surrounding the infarct play an important role in both spontaneous recovery of neurological function and in treatment-induced improvements in function. Microglia and astrocytes influence this process through direct interactions with the neurons and as major determinants of the local tissue environment. Subpopulations of peri-infarct glia proliferate early after stroke providing a possible target to modify recovery. Treatment with cell cycle inhibitors can reduce infarct volume and improve functional recovery. However, it is not known whether these inhibitors can influence neurological function or alter the responses of peri-infarct glia without reducing infarction. The present study aimed to address these issues by testing the effects of the cell cycle inhibitor, olomoucine, on recovery and peri-infarct changes following photothrombotic stroke.

Methods

Stroke was induced by photothrombosis in the forelimb sensorimotor cortex in Sprague-Dawley rats. Olomoucine was administered at 1 h and 24 h after stroke induction. Forelimb function was monitored up to 29 days. The effects of olomoucine on glial cell responses in peri-infarct tissue were evaluated using immunohistochemistry and Western blotting.

Results

Olomoucine treatment did not significantly affect maximal infarct volume. Recovery of the affected forelimb on a placing test was impaired in olomoucine-treated rats, whereas recovery in a skilled reaching test was substantially improved. Olomoucine treatment produced small changes in aspects of Iba1 immunolabelling and in the number of CD68-positive cells in cerebral cortex but did not selectively modify responses in peri-infarct tissue. The content of the astrocytic protein, vimentin, was reduced by 30% in the region of the lesion in olomoucine-treated rats.

Conclusions

Olomoucine treatment modified functional recovery in the absence of significant changes in infarct volume. The effects on recovery were markedly test dependent, adding to evidence that skilled tasks requiring specific training and general measures of motor function can be differentially modified by some interventions. The altered recovery was not associated with specific changes in key responses of peri-infarct microglia, even though these cells were considered a likely target for early olomoucine treatment. Changes detected in peri-infarct reactive astrogliosis could contribute to the altered patterns of functional recovery.

Available only for authorised users

Feigin VL, Krishnamurthi RV, Parmar P, Norrving B, Mensah GA, Bennett DA, et al. Update on the global burden of ischemic and hemorrhagic stroke in 1990-2013: The GBD 2013 Study. Neuroepidemiol. 2015;45(3):161–76. https://doi.org/10.1159/000441085.

Hossmann K-A. Pathophysiological basis of translational stroke research. Folia Neuropathol. 2009;47(3):213–27.

Moskowitz MA, Lo EH, Iadecola C. The science of stroke: Mechanisms in search of treatments. Neuron. 2010;67(2):181–98. https://doi.org/10.1016/j.neuron.2010.07.002.CrossRefPubMedPubMedCentral

Cramer SC. Treatments to promote neural repair after stroke. J Stroke. 2018;20(1):57–70. https://doi.org/10.5853/jos.2017.02796.CrossRefPubMedPubMedCentral

Murphy TH, Corbett D. Plasticity during stroke recovery: from synapse to behaviour. Nature Rev Neurosci. 2009;10(12):861–72. https://doi.org/10.1038/nrn2735.CrossRef

Nudo RJ. Recovery after brain injury: mechanisms and principles. Front Human Neurosci. 2013;7:887. https://doi.org/10.3389/fnhum.2013.00887.

Carmichael ST, Kathirvelu B, Schweppe CA, Nie EH. Molecular, cellular and functional events in axonal sprouting after stroke. Exp Neurology. 2017;287(Pt 3):384–94. https://doi.org/10.1016/j.expneurol.2016.02.007.CrossRef

Zhao L-R, Willing A. Enhancing endogenous capacity to repair a stroke-damaged brain: an evolving field for stroke research. Prog Neurobiol. 2018;163:5–26. https://doi.org/10.1016/j.pneurobio.2018.01.004.

Schroeter M, Jander S, Stoll G. Non-invasive induction of focal cerebral ischemia in mice by photothrombosis of cortical microvessels: characterization of inflammatory responses. J Neurosci Methods. 2002;117(1):43–9. https://doi.org/10.1016/S0165-0270(02)00072-9.CrossRefPubMed

10.

Morrison HW, Filosa JA. A quantitative spatiotemporal analysis of microglia morphology during ischemic stroke and reperfusion. J Neuroinflammation. 2013;10:4. https://doi.org/10.1186/1742-2094-10-4

11.

Yew WP, Djukic ND, Jayaseelan JSP, Walker FR, Roos KAA, Chataway TK, et al. Early treatment with minocycline following stroke in rats improves functional recovery and differentially modifies responses of peri-infarct microglia and astrocytes. J Neuroinflammation. 2019;16(1):6. https://doi.org/10.1186/s12974-018-1379-y.

12.

Li HL, Zhang NN, Lin HY, Yu Y, Cai QY, Ma LX, et al. Histological, cellular and behavioral assessments of stroke outcomes after photothrombosis-induced ischemia in adult mice. BMC Neurosci. 2014;15(1):58. https://doi.org/10.1186/1471-2202-15-58.

13.

Ma YY, Wang JX, Wang YT, Yang GY. The biphasic function of microglia in ischemic stroke. Prog Neurobiol. 2017;157:247–72. https://doi.org/10.1016/j.pneurobio.2016.01.005.CrossRefPubMed

14.

Rawlinson C, Jenkins S, Thei L, Dallas ML, Chen RL. Post-ischaemic immunological response in the brain: Targeting microglia in ischaemic stroke therapy. Brain Sci. 2020;10(3):159. https://doi.org/10.3390/brainsci10030159.CrossRefPubMedCentral

15.

Burda JE, Sofroniew MV. Reactive gliosis and the multicellular response to CNS damage and disease. Neuron. 2014;81(2):229–48. https://doi.org/10.1016/j.neuron.2013.12.034.CrossRefPubMedPubMedCentral

16.

Liu ZW, Chopp M. Astrocytes, therapeutic targets for neuroprotection and neurorestoration in ischemic stroke. Prog Neurobiol. 2016;144:103–20. https://doi.org/10.1016/j.pneurobio.2015.09.008.CrossRefPubMed

17.

Pekny M, Pekna M. Reactive gliosis in the pathogenesis of CNS diseases. Biochim Et Biophys Acta. 2016;1862:483–91. https://doi.org/10.1016/j.bbadis.2015.11.014.

18.

Sims NR, Yew WP. Reactive astrogliosis in stroke: contributions of astrocytes to recovery of neurological function. Neurochem Int. 2017;107:88–103. https://doi.org/10.1016/j.neuint.2016.12.016.CrossRefPubMed

19.

Barreto GE, Sun XY, Xu LJ, Giffard RG. Astrocyte proliferation following stroke in the mouse depends on distance from the infarct. PLoS One. 2011;6(11):e27881. https://doi.org/10.1371/journal.pone.0027881.CrossRefPubMedPubMedCentral

20.

Asahi M, Hoshimaru M, Uemura Y, Tokime T, Kojima M, Ohtsuka T, et al. Expression of interleukin-1 beta converting enzyme gene family and bcl-2 gene family in the rat brain following permanent occlusion of the middle cerebral artery. J Cereb Blood Flow Metab. 1997;17(1):11–8. https://doi.org/10.1097/00004647-199701000-00003.

21.

Sofroniew MV. Astrocyte barriers to neurotoxic inflammation. Nature Rev Neurosci. 2015;16(5):249–63. https://doi.org/10.1038/nrn3898.CrossRef

22.

Shimada IS, Borders A, Aronshtam A, Spees JL. Proliferating reactive astrocytes are regulated by Notch-1 in the peri-Infarct area after stroke. Stroke. 2011;42(11):3231–7. https://doi.org/10.1161/STROKEAHA.111.623280.CrossRefPubMedPubMedCentral

23.

Zhang Q, Chen C, Lu JG, Xie MJ, Pan DJ, Luo X, et al. Cell cycle inhibition attenuates microglial proliferation and production of IL-1 beta, MIP-1 alpha, and NO after focal cerebral ischemia in the rat. Glia. 2009;57(8):908–20. https://doi.org/10.1002/glia.20816.

24.

Menn B, Bach S, Blevins TL, Campbell M, Meijer L, Timsit S. Delayed treatment with systemic (S)-roscovitine provides neuroprotection and inhibits in vivo CDK5 activity increase in animal stroke models. PLoS One. 2010;5(8):e12117. https://doi.org/10.1371/journal.pone.0012117.CrossRefPubMedPubMedCentral

25.

Rousselet E, Letondor A, Menn B, Courbebaisse Y, Quille ML, Timsit S. Sustained (S)-roscovitine delivery promotes neuroprotection associated with functional recovery and decrease in brain edema in a randomized blind focal cerebral ischemia study. J Cereb Blood Flow Metab. 2018;38(6):1070–84. https://doi.org/10.1177/0271678X17712163.CrossRefPubMed

26.

Marlier Q, Jibassia F, Verteneuil S, Linden J, Kaldis P, Meijer L, et al. Genetic and pharmacological inhibition of Cdk1 provides neuroprotection towards ischemic neuronal death. Cell Death Discov. 2018;4(1):43. https://doi.org/10.1038/s41420-018-0044-7.

27.

Zhu Z, Zhang Q, Yu Z, Zhang L, Tian D, Zhu S, et al. Inhibiting cell cycle progression reduces reactive astrogliosis initiated by scratch injury in vitro and by cerebral ischemia in vivo. Glia. 2007;55:546–58 https://doi.org/10.1002/glia.20476.

28.

Wang W, Redecker C, Yu ZY, Xie MH, Tian DS, Zhang L, et al. Rat focal cerebral ischemia induced astrocyte proliferation and delayed neuronal death are attenuated by cyclin-dependent kinase inhibition. J Clin Neurosci. 2008;15(3):278–85. https://doi.org/10.1016/j.jocn.2007.02.004.

29.

Abraham RT, Acquarone M, Andersen A, Asensi A, Belle R, Berger F, et al. Cellular effects of olomoucine, an inhibitor of cyclin-dependent kinases. Biol Cell. 1995;83(2-3):105–20. https://doi.org/10.1016/0248-4900(96)81298-6.

30.

Cicenas J, Kalyan K, Sorokinas A, Jatulyte A, Valiunas D, Kaupinis A, et al. Highlights of the latest advances in research on CDK inhibitors. Cancers. 2014;6(4):2224–42. https://doi.org/10.3390/cancers6042224.

31.

Watson BD, Dietrich WD, Busto R, Wachtel MS, Ginsberg MD. Induction of reproducible brain infarction by photochemically initiated thrombosis. Ann Neurol. 1985;17(5):497–504. https://doi.org/10.1002/ana.410170513.CrossRefPubMed

32.

Carmichael ST. The 3 Rs of stroke biology: radial, relayed, and regenerative. Neurotherapeutics. 2016;13(2):348–59. https://doi.org/10.1007/s13311-015-0408-0.CrossRefPubMed

33.

Benowitz LI, Carmichael ST. Promoting axonal rewiring to improve outcome after stroke. Neurobiol Dis. 2010;37(2):259–66. https://doi.org/10.1016/j.nbd.2009.11.009.CrossRefPubMed

34.

Schallert T, Woodlee MT. Orienting and placing. In the behavior of the laboratory rat. Edited by Whishaw IQ, Kolb B. Oxford: Oxford University Press; 2005. p. 129-140.

35.

Alaverdashvili M, Moon S-K, Beckman CD, Virag A, Whishaw IQ. Acute but not chronic differences in skilled reaching for food following motor cortex devascularization vs. photothrombotic stroke in the rat. Neuroscience 2008;157:297-308. https://doi.org/10.1016/j.neuroscience.2008.09.015.

36.

Metz GA, Kolb B, Whishaw IQ. Neuropsychological tests. In the behavior of the laboratory rat. Edited by Whishaw IQ, Kolb B. Oxford: Oxford University Press; 2005:475-498.

37.

Yew WP, Djukic ND, Jayaseelan JSP, Kaidonis X, Kremer KL, Choy FC, et al. Delayed treatment with human dental pulp stem cells accelerates functional recovery and modifies responses of peri-infarct astrocytes following photothrombotic stroke in rats. Cell Transplantation. 2021;30:096368972098443. https://doi.org/10.1177/0963689720984437.

38.

Rasband WS. ImageJ. U. S. National Institutes of Health, Bethesda, Maryland USA; 1997-2018. https://imagej.nih.gov/ij/. Accessed 17 Feb 2017.

39.

Colella AD, Chegenii N, Tea MN, Gibbins IL, Williams KA, Chataway TK. Comparison of stain-free gels with traditional immunoblot loading control methodology. Anal Biochem. 2012;430(2):108–10. https://doi.org/10.1016/j.ab.2012.08.015.CrossRefPubMed

40.

Asher RA, Morgenstern DA, Fidler PS, Adcock KH, Oohira A, Braistead JE, et al. Neurocan is upregulated in injured brain and in cytokine-treated astrocytes. J Neurosci. 2000;20(7):2427–38. https://doi.org/10.1523/JNEUROSCI.20-07-02427.2000.

41.

Deguchi K, Takaishi M, Hayashi T, Oohira A, Nagotani S, Li F, et al. Expression of neurocan after transient middle cerebral artery occlusion in adult rat brain. Brain Res. 2005;1037(1-2):194–9. https://doi.org/10.1016/j.brainres.2004.12.016.

42.

Matsui F, Kawashima S, Shuo T, Yamauchi S, Tokita Y, Aono S, et al. Transient expression of juvenile-type neurocan by reactive astrocytes in adult rat brains injured by kainate-induced seizures as well as surgical incision. Neuroscience. 2002;112(4):773–81. https://doi.org/10.1016/S0306-4522(02)00136-7.

43.

Keiner S, Wurm F, Kunze A, Witte OW, Redecker C. Rehabilitative therapies differentially alter proliferation and survival of glial cell populations in the perilesional zone of cortical infarcts. Glia. 2008;56(5):516–27. https://doi.org/10.1002/glia.20632.CrossRefPubMed

44.

Liebigt S, Schlegel N, Oberland J, Witte OW, Redecker C, Keiner S. Effects of rehabilitative training and anti-inflammatory treatment on functional recovery and cellular reorganization following stroke. Exp Neurol. 2012;233(2):776–82. https://doi.org/10.1016/j.expneurol.2011.11.037.CrossRefPubMed

45.

Pena-Philippides JC, Caballero-Garrido E, Lordkipanidze T, Roitbak T. In vivo inhibition of miR-155 significantly alters post-stroke inflammatory response. J Neuroinflammation. 2016;13(1):287. https://doi.org/10.1186/s12974-016-0753-x.CrossRefPubMedPubMedCentral

46.

Schroeter M, Schiene K, Kraemer M, Hagemann G, Weigel H, Eysel UT, et al. Astroglial responses in photochemically induced focal ischemia of the rat cortex. Exp Brain Res. 1995;106(1):1–6. https://doi.org/10.1007/BF00241351.

47.

Li Y, Chen J, Zhang CL, Wang L, Lu D, Katakowski M, et al. Gliosis and brain remodeling after treatment of stroke in rats with marrow stromal cells. Glia. 2005;49(3):407–17. https://doi.org/10.1002/glia.20126.

48.

Li Y, Chopp M, Zhang ZG, Zhang RL. Expression of glial fibrillary acidic protein in areas of focal cerebral-ischemia accompanies neuronal expression of 72-KDa heat-shock protein. J Neurol Sci. 1995;128(2):134–42. https://doi.org/10.1016/0022-510X(94)00228-G.CrossRefPubMed

49.

Lopez-Valdes HE, Clarkson AN, Ao Y, Charles AC, Carmichael ST, Sofroniew MV, et al. Memantine enhances recovery from stroke. Stroke. 2014;45(7):2093–100. https://doi.org/10.1161/STROKEAHA.113.004476.

50.

Hermann DM, Chopp M. Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation. Lancet Neurol. 2012;11(4):369–80. https://doi.org/10.1016/S1474-4422(12)70039-X.CrossRefPubMedPubMedCentral

51.

Ishida A, Tamakoshi K, Hamakawa M, Shimada H, Nakashima H, Masuda T, et al. Early onset of forced impaired forelimb use causes recovery of forelimb skilled motor function but no effect on gross sensory-motor function after capsular hemorrhage in rats. Behav Brain Res. 2011;225(1):126–34. https://doi.org/10.1016/j.bbr.2011.06.036.

52.

Madinier A, Quattromani MJ, Sjolund C, Ruscher K, Wieloch T. Enriched housing enhances recovery of limb placement ability and reduces aggrecan-containing perineuronal nets in the rat somatosensory cortex after experimental stroke. PLoS One. 2014;9(3):e93121. https://doi.org/10.1371/journal.pone.0093121.CrossRefPubMedPubMedCentral

53.

Sun F, Wang XM, Mao XO, Xie L, Jin KL. Ablation of neurogenesis attenuates recovery of motor function after focal cerebral ischemia in middle-aged mice. PLoS One. 2012;7(10):e46326. https://doi.org/10.1371/journal.pone.0046326.CrossRefPubMedPubMedCentral

54.

Jeffers MS, Corbett D. Synergistic effects of enriched environment and task-specific reach training on poststroke recovery of motor function. Stroke. 2018;49(6):1496–503. https://doi.org/10.1161/STROKEAHA.118.020814.CrossRefPubMed

55.

Okabe N, Himi N, Nakamura-Maruyama E, Hayashi N, Sakamoto I, Hasegawa T, et al. Very early initiation reduces benefits of poststroke rehabilitation despite increased corticospinal projections. Neurorehab Neural Repair. 2019;33(7):538–52. https://doi.org/10.1177/1545968319850132.

56.

Ishida A, Isa K, Umeda T, Kobayashi K, Kobayashi K, Hida H, et al. Causal link between the cortico-rubral pathway and functional recovery through forced impaired limb use in rats with stroke. J Neurosci. 2016;36(2):455–67. https://doi.org/10.1523/JNEUROSCI.2399-15.2016.

57.

Bland ST, Schallert T, Strong R, Aronowski J, Grotta JC. Early exclusive use of the affected forelimb after moderate transient focal ischemia in rats - functional and anatomic outcome. Stroke. 2000;31(5):1144–51. https://doi.org/10.1161/01.STR.31.5.1144.CrossRefPubMed

58.

Muller HD, Hanumanthiah KM, Diederich K, Schwab S, Schabitz WR, Sommer C. Brain-derived neurotrophic factor but not forced arm use improves long-term outcome after photothrombotic stroke and transiently upregulates binding densities of excitatory glutamate receptors in the rat brain. Stroke. 2008;39(3):1012–21. https://doi.org/10.1161/STROKEAHA.107.495069.CrossRefPubMed

59.

Ohlsson AL, Johansson BB. Environment influences functional outcome of infarction in rats. Stroke. 1995;26(4):644–9. https://doi.org/10.1161/01.STR.26.4.644.CrossRefPubMed

60.

Auriat AM, Colbourne F. Influence of amphetamine on recovery after intracerebral hemorrhage in rats. Behav Brain Res. 2008;186(2):222–9. https://doi.org/10.1016/j.bbr.2007.08.010.CrossRefPubMed

61.

McDonald MW, Hayward KS, Rosbergen ICM, Jeffers MS, Corbett D. Is environmental enrichment ready for clinical application in human post-stroke rehabilitation? Front Behav Neurosci. 2018;12:135. https://doi.org/10.3389/fnbeh.2018.00135.CrossRefPubMedPubMedCentral

62.

Phipps MS, Cronin CA. Management of acute ischemic stroke. BMJ. 2020;368:16983 https://doi.org/10.1136/bmj.l6983.

63.

Kassem-Moussa H, Graffagnino C. Nonocclusion and spontaneous recanalization rates in acute ischemic stroke—a review of cerebral angiography studies. Arch Neurol. 2002;59(12):1870–3. https://doi.org/10.1001/archneur.59.12.1870.CrossRefPubMed

64.

Kettenmann H, Hanisch U-K, Noda M, Verkhratsky A. Physiology of microglia. Physiol Rev. 2011;91:461–553 https://doi.org/10.1152/physrev.00011.2010.

65.

Werner Y, Mass E, Kumar PA, Ulas T, Handler K, Horne A, et al. Cxcr4 distinguishes HSC-derived monocytes from microglia and reveals monocyte immune responses to experimental stroke. Nature Neurosci. 2020;23(3):351–64. https://doi.org/10.1038/s41593-020-0585-y.

66.

Li T, Pang SR, Yu YP, Wu XQ, Guo J, Zhang SX. Proliferation of parenchymal microglia is the main source of microgliosis after ischaemic stroke. Brain. 2013;136(12):3578–88. https://doi.org/10.1093/brain/awt287.CrossRefPubMed

67.

Zarruk JG, Greenhalgh AD, David S. Microglia and macrophages differ in their inflammatory profile after permanent brain ischemia. Exp Neurol. 2018;301(Pt B):120–32. https://doi.org/10.1016/j.expneurol.2017.08.011.CrossRefPubMed

68.

Damoiseaux J, Dopp EA, Calame W, Chao D, Macpherson GG, Dijkstra CD. Rat macrophage lysosomal membrane antigen recognized by monoclonal antibody ED1. Immunology. 1994;83(1):140–7.PubMedPubMedCentral

69.

Chistiakov DA, Killingsworth MC, Myasoedova VA, Orekhov AN, Bobryshev YV. CD68/macrosialin: not just a histochemical marker. Lab Invest. 2017;97(1):4–13. https://doi.org/10.1038/labinvest.2016.116.CrossRefPubMed

70.

Schroeter M, Jander S, Huitinga I, Witte OW, Stoll G. Phagocytic response in photochemically induced infarction of rat cerebral cortex - The role of resident microglia. Stroke. 1997;28(2):382–6. https://doi.org/10.1161/01.STR.28.2.382.CrossRefPubMed

71.

Scholzen T, Gerdes J. The Ki-67 protein: From the known and the unknown. J Cell Physiol. 2000;182(3):311–22. https://doi.org/10.1002/(SICI)1097-4652(200003)182:3<311::AID-JCP1>3.0.CO;2-9.

72.

Petito CK, Morgello S, Felix JC, Lesser ML. The 2 patterns of reactive astrocytosis in postischemic rat-brain. J Cereb Blood Flow Metab. 1990;10(6):850–9. https://doi.org/10.1038/jcbfm.1990.141.CrossRefPubMed

73.

Korzhevskii DE, Lentsman MV, Kirik OV, Otellin VA. Vimentin-immunopositive cells in the rat telencephalon after experimental ischemic stroke. Neurosci Behav Physiol. 2008;38(8):845–8. https://doi.org/10.1007/s11055-008-9061-y.CrossRefPubMed

74.

Marumo T, Takagi Y, Muraki K, Hashimoto N, Miyamoto S, Tanigaki K. Notch signaling regulates nucleocytoplasmic Olig2 translocation in reactive astrocytes differentiation after ischemic stroke. Neurosci Res. 2013;75(3):204–9. https://doi.org/10.1016/j.neures.2013.01.006.CrossRefPubMed

75.

Zhao BQ, Wang S, Kim HY, Storrie H, Rosen BR, Mooney DJ, et al. Role of matrix metalloproteinases in delayed cortical responses after stroke. Nature Med. 2006;12(4):441–5. https://doi.org/10.1038/nm1387.

76.

Liauw J, Hoang S, Choi M, Eroglu C, Sun GH, Percy M, et al. Thrombospondins 1 and 2 are necessary for synaptic plasticity and functional recovery after stroke. J Cereb Blood Flow Metab. 2008;28(10):1722–32. https://doi.org/10.1038/jcbfm.2008.65.

77.

Hayakawa K, Pham LDD, Katusic ZS, Arai K, Lo EH. Astrocytic high-mobility group box 1 promotes endothelial progenitor cell-mediated neurovascular remodeling during stroke recovery. Proc Natl Acad Sci U S A. 2012;109(19):7505–10. https://doi.org/10.1073/pnas.1121146109.CrossRefPubMedPubMedCentral

78.

Cekanaviciute E, Fathali N, Doyle KP, Williams AM, Han J, Buckwalter MS. Astrocytic transforming growth factor-beta signaling reduces subacute neuroinflammation after stroke in mice. Glia. 2014;62(8):1227–40. https://doi.org/10.1002/glia.22675.CrossRefPubMedPubMedCentral

79.

Liu ZW, Li Y, Cui YS, Roberts C, Lu M, Wilhelmsson U, et al. Beneficial effects of GFAP/vimentin reactive astrocytes for axonal remodeling and motor behavioral recovery in mice after stroke. Glia. 2014;62(12):2022–33. https://doi.org/10.1002/glia.22723.

80.

Jin YM, Raviv N, Barnett A, Bambakidis NC, Filichia E, Luo Y. The Shh signaling pathway Is upregulated in multiple cell types in cortical ischemia and influences the outcome of stroke in an animal model. PLoS One. 2015;10:e0126457 https://doi.org/10.1371/journal.pone.0124657.

81.

Lagace DC. Does the endogenous neurogenic response alter behavioral recovery following stroke? Behavioural Brain Research. 2012;227(2):426–32. https://doi.org/10.1016/j.bbr.2011.08.045.CrossRefPubMed

82.

Williamson MR, Jones TA, Drew MR. Functions of subventricular zone neural precursor cells in stroke recovery. Behavl Brain Res. 2019;376:112209. https://doi.org/10.1016/j.bbr.2019.112209.CrossRef

83.

Garcia-Culebras A, Duran-Laforet V, Pena-Martinez C, Ballesteros I, Pradillo JM, Diaz-Guzman J, et al. Myeloid cells as therapeutic targets in neuroinflammation after stroke: Specific roles of neutrophils and neutrophil-platelet interactions. J Cereb Blood Flow Metab. 2018;38(12):2150–64. https://doi.org/10.1177/0271678X18795789.

84.

Iadecola C, Buckwalter MS, Anrather J. Immune responses to stroke: mechanisms, modulation, and therapeutic potential. J Clin Invest. 2020;130(6):2777–88. https://doi.org/10.1172/JCI135530.CrossRefPubMedPubMedCentral

85.

Liang HX, Zhao HD, Gleichman A, Machnicki M, Telang S, Tang S, et al. Region-specific and activity-dependent regulation of SVZ neurogenesis and recovery after stroke. Proc Natl Acad Sci U S A. 2019;116(27):13621–30. https://doi.org/10.1073/pnas.1811825116.

86.

Zhang RL, Zhang ZG, Zhang L, Chopp M. Proliferation and differentiation of progenitor cells in the cortex and the subventricular zone in the adult rat after focal cerebral ischemia. Neuroscience. 2001;105(1):33–41. https://doi.org/10.1016/S0306-4522(01)00117-8.CrossRefPubMed

87.

Jin KL, Wang XM, Xie L, Mao XO, Greenberg DA. Transgenic ablation of doublecortin-expressing cells suppresses adult neurogenesis and worsens stroke outcome in mice. Proc Natl Acad Sci U S A. 2010;107(17):7993–8. https://doi.org/10.1073/pnas.1000154107.CrossRefPubMedPubMedCentral

88.

Faiz M, Sachewsky N, Gascon S, Bang KWA, Morshead CM, Nagy A. Adult neural stem cells from the subventricular zone give rise to reactive astrocytes in the cortex after stroke. Cell Stem Cell. 2015;17(5):624–34. https://doi.org/10.1016/j.stem.2015.08.002.

Title: Differential effects of the cell cycle inhibitor, olomoucine, on functional recovery and on responses of peri-infarct microglia and astrocytes following photothrombotic stroke in rats
Authors: Wai Ping Yew
Natalia D. Djukic
Jaya S. P. Jayaseelan
Richard J. Woodman
Hakan Muyderman
Neil R. Sims
Publication date: 01-12-2021
Publisher: BioMed Central
Keyword: Stroke
Published in: Journal of Neuroinflammation / Issue 1/2021
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-021-02208-w

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Differential effects of the cell cycle inhibitor, olomoucine, on functional recovery and on responses of peri-infarct microglia and astrocytes following photothrombotic stroke in rats

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2021

The balance between AIM2-associated inflammation and autophagy: the role of CHMP2A in brain injury after cardiac arrest

Tauroursodeoxycholic acid alleviates secondary injury in spinal cord injury mice by reducing oxidative stress, apoptosis, and inflammatory response

Uncovering sex differences of rodent microglia

Microglia are involved in phagocytosis and extracellular digestion during Zika virus encephalitis in young adult immunodeficient mice

Plasma and cerebrospinal fluid inflammation and the blood-brain barrier in older surgical patients: the Role of Inflammation after Surgery for Elders (RISE) study

Acute IL-1RA treatment suppresses the peripheral and central inflammatory response to spinal cord injury