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Constraint‐induced movement therapy promotes motor recovery after neonatal stroke in the absence of neural precursor activation
Author(s) -
Adams Kelsey V.,
Mahmud Neemat,
GreenHolland Madeline,
Vonderwalde Ilan,
Umebayashi Daisuke,
Sachewsky Nadia,
Coles Brenda L.,
Kooy Derek,
Morshead Cindi M.
Publication year - 2021
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.14993
Subject(s) - constraint induced movement therapy , medicine , hypoxia (environmental) , stroke (engine) , ligation , paralysis , rehabilitation , motor cortex , stroke recovery , neural stem cell , ischemia , neuroscience , anesthesia , psychology , stem cell , surgery , biology , physical therapy , mechanical engineering , chemistry , organic chemistry , stimulation , oxygen , engineering , genetics
Neonatal stroke is a leading cause of long‐term disability and currently available rehabilitation treatments are insufficient to promote recovery. Activating neural precursor cells (NPCs) in adult rodents, in combination with rehabilitation, can accelerate functional recovery following stroke. Here, we describe a novel method of constraint‐induced movement therapy (CIMT) in a rodent model of neonatal stroke that leads to improved functional outcomes, and we asked whether the recovery was correlated with expansion of NPCs. A hypoxia/ischemia (H/I) injury was induced on postnatal day 8 (PND8) via unilateral carotid artery ligation followed by systemic hypoxia. One week and two weeks post‐H/I, CIMT was administered in the form of 3 botulinum toxin (Botox) injections, which induced temporary paralysis in the unaffected limb. Functional recovery was assessed using the foot fault task. NPC proliferation was assessed using the neurosphere assay and EdU immunohistochemistry. We found that neonatal H/I injury alone expands the NPC pool by >2.5‐fold relative to controls. We determined that using Botox injections as a method to provide CIMT results in significant functional motor recovery after H/I. However, CIMT does not lead to enhanced NPC activation or migration into the injured parenchyma in vivo. At the time of functional recovery, increased numbers of proliferating inflammatory cells were found within the injured motor cortex. Together, these findings suggest that NPC activation following CIMT does not account for the observed functional improvement and suggests that CIMT‐mediated modification of the CNS inflammatory response may play a role in the motor recovery.