Ischemic Injury Does Not Stimulate Striatal Neuron Replacement Even during Periods of Active Striatal Neurogenesis

Ermine, Charlotte M.; Wright, Jordan L.; Stanić, Davor; Parish, Clare L.; Thompson, Lachlan H.

doi:10.1016/j.isci.2020.101175

Cited by 3 publications

(10 citation statements)

References 33 publications

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“…Immunohistochemistry was performed on free-floating sections as previously described [ 54 ]. Primary antibodies specific for NeuN (1:500; Abcam, ab104225, Cambridge, MA, USA) or Iba1 (1:1000; Wako, West Grove, PA, USA, 019-19741) were incubated overnight to detect neurons or microglial, respectively.…”

Section: Methodsmentioning

confidence: 99%

Focal Ischemic Injury to the Early Neonatal Rat Brain Models Cognitive and Motor Deficits with Associated Histopathological Outcomes Relevant to Human Neonatal Brain Injury

Kagan

Ermine

Frausin

et al. 2021

IJMS

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Neonatal arterial ischemic stroke is one of the more severe birth complications. The injury can result in extensive neurological damage and is robustly associated with later diagnoses of cerebral palsy (CP). An important part of efforts to develop new therapies include the on-going refinement and understanding of animal models that capture relevant clinical features of neonatal brain injury leading to CP. The potent vasoconstrictor peptide, Endothelin-1 (ET-1), has previously been utilised in animal models to reduce local blood flow to levels that mimic ischemic stroke. Our previous work in this area has shown that it is an effective and technically simple approach for modelling ischemic injury at very early neonatal ages, resulting in stable deficits in motor function. Here, we aimed to extend this model to also examine the impact on cognitive function. We show that focal delivery of ET-1 to the cortex of Sprague Dawley rats on postnatal day 0 (P0) resulted in impaired learning in a touchscreen-based test of visual discrimination and correlated with important clinical features of CP including damage to large white matter structures.

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Section: Methodsmentioning

confidence: 99%

Focal Ischemic Injury to the Early Neonatal Rat Brain Models Cognitive and Motor Deficits with Associated Histopathological Outcomes Relevant to Human Neonatal Brain Injury

Kagan

Ermine

Frausin

et al. 2021

IJMS

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“…One area where birthdating studies using BrdU have been fundamentally important is in our understanding of the proliferative response following brain injury, for example after modeling of stroke in rodents ( Ermine et al., 2020 ). These studies are built around a ‘pulse-chase’ design, where BrdU is delivered systemically to animals to birthdate dividing cells during a defined ‘pulse’ period, followed by a ‘chase’ period that allows the labeled cells time to differentiate in order to facilitate immunohistochemical phenotyping based on the expression of mature markers of cellular identity.…”

Section: Before You Beginmentioning

confidence: 99%

“…Previous studies in rodents have shown that intraperitoneal (i.p.) injection of BrdU at a dose of 50 mg/kg every 12 h is sufficient to label all dividing cells in the neurogenic subventricular zone ( Arvidsson et al., 2002 ) although 100 mg/kg is also commonly used ( Ermine et al 2020 ). The appropriate chase period should be determined based on the aim of the experiment.…”

Section: Before You Beginmentioning

confidence: 99%

“…This approach facilitates the identification of low-frequency events that may be difficult to capture using manual counting methods, including stereology based on random sampling. For complete details on the use and execution of this protocol, please refer to Ermine et al. (2020) .…”

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confidence: 99%

“…For complete details on the use and execution of this protocol, please refer to Ermine et al. (2020) .…”

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confidence: 99%

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Histological characterization and quantification of newborn cells in the adult rodent brain

2021

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Summary This protocol describes the identification and characterization of newborn cells generated in the rodent brain after injury through birthdating with the thymidine analog 5-bromo-2′-deoxyuridine, followed by immunohistochemical labeling of fixed tissue sections. We also describe a software-assisted approach for automated detection and quantification of cells in large three-dimensional tissue volumes acquired using confocal microscopy. This approach facilitates the identification of low-frequency events that may be difficult to capture using manual counting methods, including stereology based on random sampling. For complete details on the use and execution of this protocol, please refer to Ermine et al. (2020) .

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Long-term structural brain changes in adult rats after mild ischaemic stroke

Syeda

Ermine

Khilf

et al. 2022

Brain Communications

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Preclinical studies of remote degeneration have largely focused on brain changes over the first few days or weeks after stroke. Accumulating evidence suggests that neurodegeneration occurs in other brain regions remote to the site of infarction for months and even years following ischemic stroke. Brain atrophy appears to be driven by both axonal degeneration and widespread brain inflammation. The evolution and duration of these changes are increasingly being described in human studies, using advanced brain imaging techniques. Here we sought to investigate long-term structural brain changes in a model of mild focal ischemic stroke following injection of endothlin-1 in adult Long-Evans rats (n = 14) compared to sham animals (n = 10), over a clinically relevant time-frame of 48 weeks. Serial structural and diffusion-weighted MRI data were used to assess dynamic volume and white matter trajectories. We observed dynamic regional brain volume changes over the 48 weeks, reflecting both normal changes with age in sham animals and neurodegeneration in regions connected to the infarct following ischemia. Ipsilesional cortical volume loss peaked at 24 weeks but was less prominent at 36 and 48 weeks. We found significantly reduced fractional anisotropy in both ipsi- and contralesional motor cortex and cingulum bundle regions of infarcted rats (p < 0.05) from 4-36 weeks, suggesting ongoing white matter degeneration in tracts connected to but distant from the stroke. We conclude that there is evidence of significant cortical atrophy and white matter degeneration out to 48 weeks following infarct, consistent with enduring, pervasive stroke-related degeneration.

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Ischemic Injury Does Not Stimulate Striatal Neuron Replacement Even during Periods of Active Striatal Neurogenesis

Abstract: Phenotyping of thousands of cells generated after striatal ischemic injury Confirms previous reports on lack of injury-induced adult striatal neurogenesisNo ''self-repair'' even during active periods of neonatal striatal neurogenesis

Cited by 3 publications

References 33 publications

Focal Ischemic Injury to the Early Neonatal Rat Brain Models Cognitive and Motor Deficits with Associated Histopathological Outcomes Relevant to Human Neonatal Brain Injury

Focal Ischemic Injury to the Early Neonatal Rat Brain Models Cognitive and Motor Deficits with Associated Histopathological Outcomes Relevant to Human Neonatal Brain Injury

Histological characterization and quantification of newborn cells in the adult rodent brain

Long-term structural brain changes in adult rats after mild ischaemic stroke

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