Changes of Doublecortin-Immunoreactive Cells from the Acute Phase to Chronic Phase After Transient Global Brain Ischemia in Rat Cingulate Cortex

  • Kosei Goto
  • Nobuo Kutsuna
  • Akiko Yamashita
  • Hideki Oshima
  • Takeshi Suma
  • Atsuo Yoshino
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1072)


Doublecortin (DCX)-immunoreactive (-ir) cells play important roles in adult cortical remodeling. We previously reported that DCX-ir cells decrease after transient global brain ischemia (GBI) in the cingulate cortex (Cg) of rats. In the present study, we examined the changes of DCX-ir cells from the acute to the chronic phase after GBI in rats. Transient GBI was induced by a four-vessel occlusion model as described previously. Thirty-six rats were divided into six groups: day 7 after sham operation (Group Sham+A), day 7 after 3 min GBI (Group GBI3+A), day 7 after 10 min GBI (Group GBI10+A), day 90 after sham operation (Group Sham+C), day 90 after 3 min GBI (Group GBI3+C), and day 90 after 10 min GBI (Group GBI10+C). The numbers of DCX-ir cells per unit area (mm2) were investigated in the anterior cingulate cortex (ACC) and retrosplenial cortex (RS). A two-way factorial analysis of variance regarding the time of GBI (sham, GBI3, GBI10) or the period after GBI (day 7, day 90) was employed in each area. Regarding the time of GBI, there were significant differences in both the ACC and the RS (p < 0.001, respectively). Regarding the period after GBI, there was no significant difference in the ACC, whereas a significant difference was found in the RS (p = 0.005). In each area and in each phase, the numbers did not change in GBI3 (one-way ANOVA followed by a Tukey test) and decreased in GBI10 (p < 0.005). The numbers in the RS from the acute phase to chronic phase did not change in the sham and GBI3, and decreased in GBI10 (independent t-test, p < 0.001). However, histochemical staining with Fluoro-Jade B suggested that neuronal cell death did not occur in both the ACC and the RS in all groups. The present findings indicate that the cortical remodeling potential in the Cg decreases in the acute phase after GBI, and continues to decrease until the chronic phase.



We express our thanks to the Animal Housing Facility, Nihon University School of Medicine, the Division of Applied System Neuroscience, Department of Advanced Medical Science, Nihon University School of Medicine, and the Division of Anatomical Science, Department of Functional Morphology, Nihon University School of Medicine.


  1. 1.
    Francis F, Koulakoff A, Boucher D, Chafey P, Schaar B, Vinet MC, Friocourt G, McDonnell N, Reiner O, Kahn A, McConnell SK, Berwald-Netter Y, Denoulet P, Chelly J (1999) Doublecortin is a developmentally regulated, microtubule-associated protein expressed in migrating and differentiating neurons. Neuron 23:247–256CrossRefGoogle Scholar
  2. 2.
    Brown JP, Couillard-Despres S, Cooper-Kuhn CM, Winkler J, Aigner L, Kuhn HG (2003) Transient expression of doublecortin during adult neurogenesis. J Comp Neurol 467:1–10CrossRefGoogle Scholar
  3. 3.
    Friocourt G, Liu JS, Antypa M, Rakic S, Walsh CA, Parnavelas JG (2007) Both doublecortin and doublecortin-like kinase play a role in cortical interneuron migration. J Neurosci 27:3875–3883CrossRefGoogle Scholar
  4. 4.
    Kronenberg G, Reuter K, Steiner B, Brabdt MD, Jessberger S, Yamaguchi M, Kempermann G (2003) Subpopulations of proliferating cells of the adult hippocampus respond differently to physiologic neurogenic stimuli. J Comp Neurol 467:455–463CrossRefGoogle Scholar
  5. 5.
    Cai Y, Xiong K, Chu Y, Luo DW, Luo XG, Yuan XY, Struble RG, Clough RW, Spencer DD, Williamson A, Kordower JH, Patrylo PR, Yan XX (2009) Doublecortin expression in adult cat and primate cerebral cortex relates to immature neurons that develop into GABAergic subgroups. Exp Neurol 216:342–356CrossRefGoogle Scholar
  6. 6.
    Kutsuna N, Suma T, Takada Y, Yamashita A, Oshima H, Sakatani K, Yamamoto T, Katayama Y (2012) Decrease in doublecortin expression without neuronal cell death in rat retrosplenial cortex after stress exposure. Neuroreport 23:211–215CrossRefGoogle Scholar
  7. 7.
    Kutsuna N, Murata Y, Eriguchi T, Takada Y, Oshima H, Sakatani K, Katayama Y (2013) DCX-expressing neurons decrease in the retrosplenial cortex after global brain ischemia. Adv Exp Med Biol 765:115–121CrossRefGoogle Scholar
  8. 8.
    Kutsuna N, Yamashita A, Eriguchi T, Oshima H, Suma T, Sakatani K, Yamamoto T, Yoshino A, Katayama Y (2014) Acute stress exposure preceding transient global brain ischemia exacerbates the decrease in cortical remodeling potential in the rat retrosplenial cortex. Neurosci Res 78:65–71CrossRefGoogle Scholar
  9. 9.
    Nicholson BD (2004) Evaluation and treatment of cerebral pain syndromes. Neurology 62:S30–S36CrossRefGoogle Scholar
  10. 10.
    Tahta K, Cirak B, Pakdemiri E, Suzer T, Tahta F (2007) Postoperative mutism after removal of an anterior falcine meningioma. J Clin Neurosci 14:793–796CrossRefGoogle Scholar
  11. 11.
    Yagita Y, Kitagawa K, Otsuki T, Takasawa K, Miyata T, Okano H, Hori M, Matsumoto M (2001) Neurogenesis by progenitor cells in the ischemic adult rat hippocampus. Stroke 32:1890–1896CrossRefGoogle Scholar
  12. 12.
    Paxinos G, Eatson C (2008) The rat brain in stereotaxic coordinators: compact, 6th edn. Academic, New YorkGoogle Scholar
  13. 13.
    Schmued LC, Hopkins KJ (2000) Fluoro-jade B: a high affinity fluorescent marker for the localization of neuronal degeneration. Brain Res 874:123–130CrossRefGoogle Scholar
  14. 14.
    Zhou AM, Li WB, Li QJ, Liu HQ, Feng RF, Zhao HG (2004) A short cerebral ischemic preconditioning up-regulates adenosine receptors in the hippocampal CA1 region of rats. Neurosci Res 48:397–404CrossRefGoogle Scholar
  15. 15.
    Von Bohlen H (2007) Immunohistological markers for staging neurogenesis in adult hippocampus. Cell Tissue Res 329:409–420CrossRefGoogle Scholar
  16. 16.
    Kawaguchi Y, Kondo S (2002) Parvalbumin, somatostatin and cholecystokinin as chemical markers for specific GABAergic interneuron types in the rat frontal cortex. J Neurocytol 31:277–287CrossRefGoogle Scholar
  17. 17.
    Kubota Y (2014) Untangling GABAergic wiring in the cortical microcircuit. Curr Opin Neurobiol 26:7–14CrossRefGoogle Scholar
  18. 18.
    Xie Y, Chen S, Wu Y, Murphy TH (2014) Prolonged deficits in parvalbumin neuron stimulation-evoked network activity despite recovery of dendritic structure and excitability in mice. J Neuro-Oncol 34:14890–14900Google Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Kosei Goto
    • 1
  • Nobuo Kutsuna
    • 1
  • Akiko Yamashita
    • 2
  • Hideki Oshima
    • 1
  • Takeshi Suma
    • 1
  • Atsuo Yoshino
    • 1
  1. 1.Division of Neurosurgery, Department of Neurological SurgeryNihon University School of MedicineTokyoJapan
  2. 2.Division of Biology, Department of Liberal EducationNihon University School of MedicineTokyoJapan

Personalised recommendations