Correlates of Post-Stroke Brain Plasticity, Relationship to Pathophysiological Settings and Implications for Human Proof-of-Concept Studies

Abstract

The promotion of neurological recovery by enhancing neuroplasticity has recently obtained strong attention in the stroke field. Experimental studies support the hypothesis that stroke recovery can be improved by therapeutic interventions that augment neuronal sprouting. However plasticity responses of neurons are highly complex, involving the growth and differentiation of axons, dendrites, dendritic spines and synapses, which depend on the pathophysiological setting and are tightly controlled by extracellular and intracellular signals. Thorough mechanistic insights are needed into how neuronal plasticity is influenced by plasticity-promoting therapies in order not to risk the success of future clinical proof-of-concept studies.

Dose-Dependent Microglial and Astrocytic Responses Associated With Post-ischemic Neuroprotection After Lipopolysaccharide-Induced Sepsis-Like State in Mice

“…In line with the recently discovered cross-talk between microglia and astrocytes during neuroinflammation (Rothhammer et al, 2018;Vainchtein et al, 2018;Wheeler et al, 2019), we observed that LPS injection increased astroglial GFAP reactivity. Based on the detrimental outcome of impaired astrogliosis on axon regeneration (Anderson et al, 2016), this elevated astrocytic response may contribute to restorative mechanisms that support neurological recovery.…”

“…Flow cytometry and cytokine measurements are valuable for evaluating neuroinflammatory responses but lack spatial information. In the context of focal cerebral ischemia, it is essential to know the spatial pattern of glial reactivity because it can affect post-stroke neural plasticity in regions which are distant from the stroke lesion (Hermann and Chopp, 2012;Sanchez-Mendoza and Hermann, 2016;Ma et al, 2017). Our approach allows comparing microglia activation in the lesion core with the adjacent and distant perilesional areas.…”

Improved functional outcome after chronic stroke with delayed anti-Nogo-A therapy: A clinically relevant intention-to-treat analysis

“…To our knowledge, the present study is the first strict ITT analysis of anti-Nogo-A efficacy at a clinically relevant chronic time point and in a population that includes animals with severe and very severe stroke deficits and corresponding large stroke sizes. Based on these results, we can conclude that anti-Nogo-A immunotherapy is effective chronically after stroke and after the lesion-induced neuroplasticity-promoting environment in the brain is thought to have diminished, 44 , 45 thereby validating our previous report. 28 …”

Effects of High-Frequency Repetitive Transcranial Magnetic Stimulation Combined with Task-Oriented Mirror Therapy Training on Hand Rehabilitation of Acute Stroke Patients

“…In the case of brain stroke patients, although recovery depends on the location and extent of the damage, recovery can be expedited if treatment is provided during the initial 3 months after the stroke. Thereafter, the recovery time increases with the passage of time, and neurological recovery stagnates after 1 year [ 24 ]. Therefore, providing rehabilitation treatment in the initial stage immediately after the stroke is very important.…”