Reduced microglia activation following metformin administration or microglia ablation is sufficient to prevent functional deficits in a mouse model of neonatal stroke.

Background: Neonatal stroke is a devastating insult that can lead to life-long impairments. In response to hypoxic-ischaemic injury, there is loss of neurons and glia as well as a neuroinflammatory response mediated by resident immune cells, including microglia and astrocytes, which can exacerbate damage. Administration of the antidiabetic drug metformin has been shown to improve functional outcomes in preclinical models of brain injury and the cellular basis for metformin-mediated recovery is unknown.

Constraint-induced movement therapy promotes motor recovery after neonatal stroke in the absence of neural precursor activation.

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.

Age- and sex-dependent effects of metformin on neural precursor cells and cognitive recovery in a model of neonatal stroke.

Resident neural stem and progenitor cells, collectively termed neural precursor cells (NPCs), reside in a well-defined neurogenic niche in the subventricular zone (SVZ) and contribute to ongoing postnatal neurogenesis. It is well established that the NPC niche can alter the behavior of NPCs. NPC activation is a promising therapeutic strategy for brain repair.

Neural stem cell heterogeneity in the mammalian forebrain.

The brain was long considered an organ that underwent very little change after development. It is now well established that the mammalian central nervous system contains neural stem cells that generate progeny that are capable of making new neurons, astrocytes, and oligodendrocytes throughout life. The field has advanced rapidly as it strives to understand the basic biology of these precursor cells, and explore their potential to promote brain repair.