Post-stroke Neurogenesis: Friend or Foe?

Abstract

The substantial clinical burden and disability after stroke injury urges the need to explore therapeutic solutions. Recent compelling evidence supports that neurogenesis persists in the adult mammalian brain and is amenable to regulation in both physiological and pathological situations. Its ability to generate new neurons implies a potential to contribute to recovery after brain injury. However, post-stroke neurogenic response may have different functional consequences. On the one hand, the capacity of newborn neurons to replenish the damaged tissue may be limited. In addition, aberrant forms of neurogenesis have been identified in several insult settings. All these data suggest that adult neurogenesis is at a crossroads between the physiological and the pathological regulation of the neurological function in the injured central nervous system (CNS). Given the complexity of the CNS together with its interaction with the periphery, we ultimately lack in-depth understanding of the key cell types, cell–cell interactions, and molecular pathways involved in the neurogenic response after brain damage and their positive or otherwise deleterious impact. Here we will review the evidence on the stroke-induced neurogenic response and on its potential repercussions on functional outcome. First, we will briefly describe subventricular zone (SVZ) neurogenesis after stroke beside the main evidence supporting its positive role on functional restoration after stroke. Then, we will focus on hippocampal subgranular zone (SGZ) neurogenesis due to the relevance of hippocampus in cognitive functions; we will outline compelling evidence that supports that, after stroke, SGZ neurogenesis may adopt a maladaptive plasticity response further contributing to the development of post-stroke cognitive impairment and dementia. Finally, we will discuss the therapeutic potential of specific steps in the neurogenic cascade that might ameliorate brain malfunctioning and the development of post-stroke cognitive impairment in the chronic phase.

Targeting the Erk1/2 and autophagy signaling easily improved the neurobalst differentiation and cognitive function after young transient forebrain ischemia compared to old gerbils

“…Hippocampal neurogenesis has been shown to be an important event in cognitive and neurological recovery [ 32 , 46 , 47 ]. Its increased neurogenesis and neuroplasticity significantly improve memory spatial learning capacity and neurorehabilitation capacity [ 48 , 49 ].…”

“…However, its recovery of neurological function and cognition and memory was mainly faster than those in the old gerbils. It is well known that recovery of neurological function and cognition and memory was closely related to neurogenesis in the dentate gyrus of hippocampus after transient cerebral ischemia [ 32 – 34 ]. Therefore, in the present study, we investigate the difference of neurogenesis and related proteins in the dentate gyrus of hippocampus after transient cerebral ischemia between young (2-month-old) and old (15-month-old) gerbils to explore the reason why the recovery of neurological function and congnition and memory was faster in young.…”

Robot-Assisted Training for Upper Limb in Stroke (ROBOTAS): An Observational, Multicenter Study to Identify Determinants of Efficacy

“…Recovery from a stroke event is a complex process entailing both spontaneous and motorpractice-mediated processes. Partial structural and functional impairments likely recover through a potentiation and extension of residual brain areas, whereas complete lesions of specific brain areas require a substitution by functionally related systems [19][20][21].…”

“…It is fundamental to be aware of such processes and related outcomes to better understand when to expect recovery, plan the most appropriate treatment, and determine the timing of rehabilitation. Although it is widely recognized that spontaneous behavioral recovery mostly occurs within the first three months after stroke, different patterns of recovery may then emerge depending on many complex factors [19]. Indeed, chronic stroke patients may still experience functional recovery through promoting cerebral plasticity, as evaluated by transcranial magnetic stimulation, EEG [22], and advanced neuroimaging techniques [23].…”

3D Reconstitution of the Neural Stem Cell Niche: Connecting the Dots

“…By accommodating all those factors, we strongly believe that this in vitro model will be closely be comparable to the in vivo analog. This SVZ in vitro model could also be utilized for the study of specific diseases whose pathophysiology is linked to the SVZ, such as CH, stroke, poststroke SVZ neurogenesis (Cuartero et al, 2021), and SVZoriginating glioblastoma (Bardella et al, 2018).…”