Perilesional Gliosis Is Associated with Outcome after Perinatal Stroke

Sabrina Yu; Charissa Lam; Siddharth Shinde; Andrea M. Kuczynski; Helen L. Carlson; Sean P. Dukelow; Brian L. Brooks; Adam Kirton

doi:10.1055/s-0041-1728687

Journal of Pediatric Neurology, Table of Contents

Journal of Pediatric Neurology 2021; 19(05): 321-329
DOI: 10.1055/s-0041-1728687

Original Article

Perilesional Gliosis Is Associated with Outcome after Perinatal Stroke

Sabrina Yu

¹Department of Pediatrics, University of Calgary, Calgary, Canada

,

Charissa Lam

¹Department of Pediatrics, University of Calgary, Calgary, Canada

,

Siddharth Shinde

¹Department of Pediatrics, University of Calgary, Calgary, Canada

,

Andrea M. Kuczynski

¹Department of Pediatrics, University of Calgary, Calgary, Canada

,

Helen L. Carlson

¹Department of Pediatrics, University of Calgary, Calgary, Canada

²Hotchkiss Brain Institute, University of Calgary, Calgary, Canada

³Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Canada

,

Sean P. Dukelow

²Hotchkiss Brain Institute, University of Calgary, Calgary, Canada

⁶Department of Radiology, University of Calgary, Calgary, Canada

,

Brian L. Brooks

¹Department of Pediatrics, University of Calgary, Calgary, Canada

²Hotchkiss Brain Institute, University of Calgary, Calgary, Canada

³Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Canada

⁴Department of Psychology, University of Calgary, Calgary, Canada

,

Adam Kirton

¹Department of Pediatrics, University of Calgary, Calgary, Canada

²Hotchkiss Brain Institute, University of Calgary, Calgary, Canada

³Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Canada

⁵Department of Clinical Neuroscience, University of Calgary, Calgary, Canada

⁶Department of Radiology, University of Calgary, Calgary, Canada

› Author Affiliations

Abstract

Perinatal ischemic stroke results in focal brain injury and life-long disability. Hemiplegic cerebral palsy and additional sequelae are common. With no prevention strategies, improving outcomes depends on understanding brain development. Reactive astrogliosis is a hallmark of brain injury that has been associated with outcomes but is unstudied in perinatal stroke. In this article, we hypothesized that gliosis was quantifiable and its extent would inversely correlate with clinical motor function. This was a population-based, retrospective, and cross-sectional study. Children with perinatal arterial ischemic stroke (AIS) or periventricular venous infarction (PVI) with magnetic resonance (MR) imaging were included. An image thresholding technique based on image intensity was utilized to quantify the degree of chronic gliosis on T2-weighted sequences. Gliosis scores were corrected for infarct volume and compared with the Assisting Hand and Melbourne Assessments (AHA and MA), neuropsychological profiles, and robotic measures. In total, 42 children were included: 25 with AIS and 17 with PVI (median = 14.0 years, range: 6.3–19 years, 63% males). Gliosis was quantifiable in all scans and scores were highly reliable. Gliosis scores as percentage of brain volume ranged from 0.3 to 3.2% and were comparable between stroke types. Higher gliosis scores were associated with better motor function for all three outcomes in the AIS group, but no association was observed for PVI. Gliosis can be objectively quantified in children with perinatal stroke. Associations with motor outcome in arterial but not venous strokes suggest differing glial responses may play a role in tissue remodeling and developmental plasticity following early focal brain injury.

Keywords

perinatal stroke - gliosis - neuroimaging - cerebral palsy - cognition

Full Text

References

References
1 Raju TN, Nelson KB, Ferriero D, Lynch JK. NICHD-NINDS Perinatal Stroke Workshop Participants. Ischemic perinatal stroke: summary of a workshop sponsored by the National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke. Pediatrics 2007; 120 (03) 609-616
2 Kirton A, Deveber G. Life after perinatal stroke. Stroke 2013; 44 (11) 3265-3271
3 Dunbar M, Kirton A. Perinatal stroke: mechanisms, management, and outcomes of early cerebrovascular brain injury. Lancet Child Adolesc Health 2018; 2 (09) 666-676
4 Mineyko A, Kirton A. The black box of perinatal ischemic stroke pathogenesis. J Child Neurol 2011; 26 (09) 1154-1162
5 Kirton A, Deveber G, Pontigon AM, Macgregor D, Shroff M. Presumed perinatal ischemic stroke: vascular classification predicts outcomes. Ann Neurol 2008; 63 (04) 436-443
6 Craig BT, Hilderley A, Kirton A, Carlson HL. Imaging developmental and interventional plasticity following perinatal stroke. Can J Neurol Sci J
7 Baker K, Carlson HL, Zewdie E, Kirton A. Developmental remodelling of the motor cortex in hemiparetic children with perinatal stroke. Pediatr Neurol 2020; 112: 34-43
8 Bandera E, Botteri M, Minelli C, Sutton A, Abrams KR, Latronico N. Cerebral blood flow threshold of ischemic penumbra and infarct core in acute ischemic stroke: a systematic review. Stroke 2006; 37 (05) 1334-1339
9 Wang Q, Tang XN, Yenari MA. The inflammatory response in stroke. J Neuroimmunol 2007; 184 (1-2): 53-68
10 Ferriero DM. Neonatal brain injury. N Engl J Med 2004; 351 (19) 1985-1995
11 Huang L, Wu Z-B, Zhuge Q. et al. Glial scar formation occurs in the human brain after ischemic stroke. Int J Med Sci 2014; 11 (04) 344-348
12 Tachibana M, Ago T, Wakisaka Y. et al. Early reperfusion after brain ischemia has beneficial effects beyond rescuing neurons. Stroke 2017; 48 (08) 2222-2230
13 Hu R, Zhou J, Luo C. et al. Glial scar and neuroregeneration: histological, functional, and magnetic resonance imaging analysis in chronic spinal cord injury. J Neurosurg Spine 2010; 13 (02) 169-180
14 Monje ML, Toda H, Palmer TD. Inflammatory blockade restores adult hippocampal neurogenesis. Science 2003; 302 (5651): 1760-1765
15 Faustino JV, Wang X, Johnson CE. et al. Microglial cells contribute to endogenous brain defenses after acute neonatal focal stroke. J Neurosci 2011; 31 (36) 12992-13001
16 Anderson MA, Burda JE, Ren Y. et al. Astrocyte scar formation aids central nervous system axon regeneration. Nature 2016; 532 (7598): 195-200
17 Willmore LJ. Post-traumatic seizures. Neurol Clin 1993; 11 (04) 823-834
18 Yun C-H, Lee SK, Lee SY, Kim KK, Jeong SW, Chung C-K. Prognostic factors in neocortical epilepsy surgery: multivariate analysis. Epilepsia 2006; 47 (03) 574-579
19 Fernández-López D, Faustino J, Klibanov AL. et al. Microglial cells prevent hemorrhage in neonatal focal arterial stroke. J Neurosci 2016; 36 (10) 2881-2893
20 Salmaso N, Jablonska B, Scafidi J, Vaccarino FM, Gallo V. Neurobiology of premature brain injury. Nat Neurosci 2014; 17 (03) 341-346
21 Janz P, Schwaderlapp N, Heining K. et al. Early tissue damage and microstructural reorganization predict disease severity in experimental epilepsy. eLife 2017; 6: e25742
22 Wagenaar N, de Theije CGM, de Vries LS, Groenendaal F, Benders MJNL, Nijboer CHA. Promoting neuroregeneration after perinatal arterial ischemic stroke: neurotrophic factors and mesenchymal stem cells. Pediatr Res 2018; 83 (1-2): 372-384
23 Singhal S, Lawrence JM, Bhatia B. et al. Chondroitin sulfate proteoglycans and microglia prevent migration and integration of grafted Müller stem cells into degenerating retina. Stem Cells 2008; 26 (04) 1074-1082
24 Suhonen JO, Peterson DA, Ray J, Gage FH. Differentiation of adult hippocampus-derived progenitors into olfactory neurons in vivo. Nature 1996; 383 (6601): 624-627
25 Kirton A, Shroff M, Visvanathan T, deVeber G. Quantified corticospinal tract diffusion restriction predicts neonatal stroke outcome. Stroke 2007; 38 (03) 974-980
26 Kitchen L, Westmacott R, Friefeld S. et al. The pediatric stroke outcome measure: a validation and reliability study. Stroke 2012; 43 (06) 1602-1608
27 Krumlinde-Sundholm L, Holmefur M, Kottorp A, Eliasson A-C. The Assisting Hand Assessment: current evidence of validity, reliability, and responsiveness to change. Dev Med Child Neurol 2007; 49 (04) 259-264
28 Bourke-Taylor H. Melbourne assessment of unilateral upper limb function: construct validity and correlation with the pediatric evaluation of disability inventory. Dev Med Child Neurol 2003; 45 (02) 92-96
29 Kuczynski AM, Semrau JA, Kirton A, Dukelow SP. Kinesthetic deficits after perinatal stroke: robotic measurement in hemiparetic children. J Neuroeng Rehabil 2017; 14 (01) 13
30 Kuczynski AM, Dukelow SP, Semrau JA, Kirton A. Robotic quantification of position sense in children with perinatal stroke. Neurorehabil Neural Repair 2016; 30 (08) 762-772
31 Dukelow SP, Herter TM, Moore KD. et al. Quantitative assessment of limb position sense following stroke. Neurorehabil Neural Repair 2010; 24 (02) 178-187
32 Semrau JA, Herter TM, Scott SH, Dukelow SP. Robotic identification of kinesthetic deficits after stroke. Stroke 2013; 44 (12) 3414-3421
33 Coderre AM, Zeid AA, Dukelow SP. et al. Assessment of upper-limb sensorimotor function of subacute stroke patients using visually guided reaching. Neurorehabil Neural Repair 2010; 24 (06) 528-541
34 Essig M, Wenz F, Schoenberg SO, Debus J, Knopp MV, Van Kaick G. Arteriovenous malformations: assessment of gliotic and ischemic changes with fluid-attenuated inversion-recovery MRI. Invest Radiol 2000; 35 (11) 689-694
35 Hao X-Z, Yin L-K, Zhang X-X. et al. Combining systemic and stereotactic MEMRI to detect the correlation between gliosis and neuronal connective pathway at the chronic stage after stroke. J Neuroinflammation 2016; 13 (01) 156
36 Weber RA, Chan CH, Nie X. et al. Sensitivity of diffusion MRI to perilesional reactive astrogliosis in focal ischemia. NMR Biomed 2017;30(07):
37 Riddle A, Dean J, Buser JR. et al. Histopathological correlates of MRI-Defined chronic perinatal white matter injury. Ann Neurol 2011; 70 (03) 493-507
38 Weidenheim KM, Epshteyn I, Rashbaum WK, Lyman WD. Patterns of glial development in the human foetal spinal cord during the late first and second trimester. J Neurocytol 1994; 23 (06) 343-353
39 Sizonenko SV, Camm EJ, Dayer A, Kiss JZ. Glial responses to neonatal hypoxic-ischemic injury in the rat cerebral cortex. Int J Dev Neurosci 2008; 26 (01) 37-45
40 Yu S, Carlson HL, Mineyko A. et al. Bihemispheric alterations in myelination in children following unilateral perinatal stroke. Neuroimage Clin 2018; 20: 7-15
41 Back SA. White matter injury in the preterm infant: pathology and mechanisms. Acta Neuropathol 2017; 134 (03) 331-349
42 Kriz J. Inflammation in ischemic brain injury: timing is important. Crit Rev Neurobiol 2006; 18 (1-2): 145-157
43 Kuczynski AM, Dukelow SP, Hodge JA. et al. Corticospinal tract diffusion properties and robotic visually guided reaching in children with hemiparetic cerebral palsy. Hum Brain Mapp 2018; 39 (03) 1130-1144