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Updated: Jul 14, 2026
Transient Middle Cerebral Artery Occlusion Model of Neonatal Stroke in P10 Rats
Published on: April 21, 2017
Bilateral changes after neonatal ischemia in the P7 rat brain
Maria Spiegler1, Sonia Villapol, Valérie Biran
1Université Pierre et Marie Curie-Paris6, Unité Mixte de Recherche-Centre National de la Recherche Scientifique 7102, Paris, France.
Insights
Neonatal ischemic brain injury in rats caused lasting damage but also stimulated neurogenesis (new neuron formation) in both hemispheres, aiding recovery. This study highlights the brain
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Cerebrovascular Research
Background:
- Adult neurogenesis occurs in the subventricular zone (SVZ) and subgranular zone (SGZ).
- Brain injury can stimulate adult neurogenesis.
Purpose of the Study:
- To investigate the effects of neonatal ischemic injury on brain damage, cell death, proliferation, and neurogenesis.
- To examine the long-term consequences of ischemic injury on hemispheric development and recovery.
Main Methods:
- Neonatal rats (postnatal day 7) underwent middle cerebral artery electrocoagulation and common carotid artery occlusion to induce ischemic injury.
- Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and immunohistochemistry for Ki-67 (proliferation) and doublecortin (immature neurons) were used.
- Histological analysis was performed from 4 hours to 6 weeks post-injury.
Main Results:
- Ischemic injury caused persistent ipsilateral (IL) and transient contralateral (CL) hemispheric area reduction due to cell death.
- Three peaks of cell proliferation (Ki-67+) were observed in the SVZ and SGZ on both sides at 48 hours, 7 days, and 28 days post-injury.
- While most proliferating cells were astrocytes early on, doublecortin staining indicated stimulated neurogenesis in the SVZ from 7-14 days, with immature neurons near the lesion.
Conclusions:
- Neonatal ischemic injury induces lasting hemispheric damage but also triggers compensatory neurogenic responses.
- Stimulated neurogenesis in both hemispheres, particularly in the SVZ, suggests a regenerative capacity following early-life brain injury.
- Despite unilateral damage, regenerative changes in the contralateral hemisphere contribute to anatomical recovery.
Abstract:
Neurogenesis persists throughout life in the rodent subventricular zone (SVZ) and subgranular zone (SGZ) and increases in the adult after brain injury. In this study, postnatal day 7 rats underwent middle cerebral artery electrocoagulation and transient homolateral common carotid artery occlusion, a lesioning protocol that resulted in ipsilateral (IL) forebrain ischemic injury, leading to a cortical cavity 3 weeks later. The effects of neonatal ischemia on hemispheric damage, cell death, cell proliferation, and neurogenesis were examined 4 hours to 6 weeks later by the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay and immunohistochemistry of Ki-67 in proliferating cells and of doublecortin, a microtubule-associated protein expressed only by immature neurons. Neonatal ischemic injury resulted in persistent reduced IL and transient reduced contralateral (CL) hemispheric areas, a consequence of sustained and transient cell death in the IL and CL areas, respectively. Ki-67 immunostaining revealed 3 peaks of newly generated cells in the dorsal SVZ and SGZ in the IL side and also in the CL side at 48 hours and 7 and 28 days after ischemia. Double immunofluorescence revealed that most of the Ki-67-positive cells were astrocytes at 48 hours. Ischemic injury also stimulated SVZ neurogenesis, based on increased doublecortin immunostaining in both SVZs at 7 to 14 days after injury. Doublecortin-positive neurons remained visible around the lesion at 21 days but displayed an immature shape in discrete chains or clusters. Although unilateral ischemic damage was produced, results indicate successful regenerative changes in the CL hemisphere, allowing anatomical recovery.
