Morphometric evaluation of the astrocytes reactivity in preterm and term infants with infectious diseases

Objective: the aim of our work is to describe a condition of the reactive astrocytes in the white matter in preterm and term infants with infectious diseases.

Materials and methods: postmortem investigation of periventricular white matter performed on material from 56 children, 35 of them were born preterm (24–36 weeks gestation).
Twenty-five children diagnosed with various infectious diseases, other have had clinical signs of hypoxic-ischemic brain injury. Immunohistochemical expression of glial fibrillary acidic protein was used as a marker for reactive astrocyte. We estimated the degree of the astrocytes reactivity, according to the mean percentage of the marker expression in anterior and posterior horns of the lateral ventricles: stage 0 – 0–1,4%, I stage – 1,5–6%, II stage – 6,1–15%, III stage – above 15,1%.

Results: comparison of the morphometric marks of the white matter showed no significant differences between groups with infections and hypoxic pathology. In 54.84% of children born at 24–33 weeks gestation determined weak stage of astroglial reactivity. Whereas due to maturation of astrocytes in children born after 34 weeks of gestation more common moderate and severe stages of astrocytes reactivity (collectively, 69,6%) was detected. Severe stage of the reactive astrocytes accompanied by the development of necrotic lesions in the periventricular white matter in 64,3% of cases, in our opinion, as a result of progressive degenerative process in glial cells. The remaining cases relates to the severe telencephalic leukoencephalopathy, perhaps some of them may contain undiagnosed necrosis outside of the white matter regions estimated in our study.

Conclusion: morphometric study of the periventricular white matter using a marker of astrocytes allows to assess their reactive changes and to perform differential diagnosis of main forms of white matter injury in infants.

1. Li J, Ramenaden R, Peng J, Koito H, Volpe JJ, Rosenberg PA. Tumor Necrosis Factor α mediates lipopolysaccharide-induced microglial toxicity to developing oligodendrocytes when astrocytes are present. J Neurosci. 2008 May; 28(20): 5321–30.

2. Sun D, Jakobs TC. Structural remodeling of astrocytes in the injured CNS. Neuroscientist. 2012 Dec; 18(6): 567–88.

3. Sun D, Lye-Barthel M, Masland RH, Jakobs TC. Structural remodeling of fibrous astrocytes after axonal injury. J Neurosci. 2010 Oct; 30(42): 14008–14019.

4. Myer DJ, Gurkoff GG, Lee SM, Hovda DA, Sofroniew MV. Essential protective roles of reactive astrocytes in traumatic brain injury. Brain. 2006 Jul; 129: 2761–2772.

5. Sofroniew MV, Vinters HV. Astrocytes: biology and pathology. Acta Neuropathol. 2010 Dec; 119: 7–35.

6. Wilhelmsson U, Li L, Pekna M, Berthold C-H, et al. Absence of glial fibrillary acidic protein and vimentin prevents hypertrophy of astrocytic processes and improves post-traumatic regeneration. J Neurosci. 2004 May; 24(21): 5016–5021.

7. Gilles FH, Murphy SF. Perinatal telencephalic leucoencephalopathy. Neurol Neurosurg Psychiat. 1969; 32(5): 404–413.

8. Eng LF, Ghirnikar RS, Lee YL. Glial fibrillary acidic protein: GFAP thirty-one years (1969 – 2000). Neurochem Res. 2000 Oct; 25(9-10): 1439–51.

9. Bush TG, Puvanachandra N, Horner CH, et al. Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic. Neuron. 1999 Jun; 23: 297–308.

10. Chen Y, Vartiainen NE, Ying W, Chan PH, Koistinaho J, Swanson RA. Astrocytes protect neurons from nitric oxide toxicity by glutathione-dependent mechanism. J Neurochem. 2001 March; 77: 1601–1610.

11. Lau LT, Yu C-H. Astrocytes produce and release Interleukin-1, Interleukin-6, Tumor Necrosis Factor Alpha and Interferon-Gamma following traumatic and metabolic injury. J Neurotrauma. 2001; 18(3): 351–359.

12. Sofroniew MV. Molecular dissection of reactive astrogliosis and glial scar formation. Trends Neurosci. 2009 Dec; 32(12): 638–647.

13. Drögemüller K, Helmuth U, Brunn A, et al. Astrocyte gp130 expression is critical for the control of Toxoplasma encephalitis. J Immunol. 2008; 181(4): 2683–2693.

14. Vlasyuk V.V. The pathology of children’s brain – in infections, hypoxic-ischemic injury and malformations. Saint-Petersburg; 2012 (in Russian).

15. Wilhelmsson U, Bushong EA, Price DL, et al. Redefining the concept of reactive astrocytes as cells that remain within their unique domains upon reaction to injury. PNAS. 2006 Nov; 103(46): 17513–17518.

16. Volpe JJ. Neurology of the newborn. Philadelphia: Elsevier Health Sciences; c 2008. 1094 p.

17. Back SA, Riddle A, McClure MM. Maturation-dependent vulnerability of perinatal white matter in premature birth. Stroke. 2007 Nov; 38(2): 724–730.

18. Back SA, Han BH, Luo NL, et al. Selective vulnerability of late oligodendrocyte progenitors to hypoxia-ischemia. J Neurosci. 2002 Jan; 22(2): 455–463.

19. Back SA, Luo NL, Borenstein NS, et al. Late oligodendrocyte progenitors coincide with the developmental window of vulnerability for human perinatal white matter injury. J Neurosci. 2001 Feb; 21(4): 1302–1312.

20. Khwaja O, Volpe JJ. Pathogenesis of cerebral white matter injury of prematurity. Arch Dis Child Fetal Neonatal Ed. 2008 March; 93(2): F153–F161.