
==== Front
Eur J Phys Rehabil Med
Eur J Phys Rehabil Med
EJPRM
European Journal of Physical and Rehabilitation Medicine
1973-9087
1973-9095
Edizioni Minerva Medica

39205485
8679
10.23736/S1973-9087.24.08679-9
Article
Stroke and neuroplasticity: harnessing the brain’s adaptive potential for recovery
FERRIERO Giorgio 1 2 *
NEGRINI Francesco 1 2
SALGOVIC Ludovit 3
RONCONI Gianpaolo 4
1Physical and Rehabilitation Medicine Unit, Istituti Clinici Scientifici Maugeri, Institute of Tradate, IRCCS, Tradate, Varese, Italy; 2Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy; 3Department of Clinical Disciplines, Institute of Physiotherapy, Balneology and Medical Rehabilitation, University of Ss. Cyril and Methodius, Trnava, Slovak Republic; 4University Polyclinic Foundation A. Gemelli IRCCS, Rome, Italy
* Corresponding author: Giorgio Ferriero, Physical and Rehabilitation Medicine Unit, Istituti Clinici Scientifici Maugeri, Institute of Tradate, IRCCS, Tradate (VA), Italy. E-mail: giorgio.ferriero@icsmaugeri.it
Authors’ contributions: All authors read and approved the final version of the manuscript.

28 8 2024
8 2024
60 4 549551
22 7 2024
22 7 2024
2024 THE AUTHORS
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (CC BY-NC-ND) 4.0 License.
==== Body
pmcIn the ever-evolving landscape of rehabilitation for neurological disorders, one concept has gained significant traction in recent years: neuroplasticity. Defined as the nervous system’s ability to reorganize and regenerate in response to new information or injury, neuroplasticity offers a beacon of hope for patients suffering from neuromotor disabilities, particularly those resulting from stroke. Traditionally, it was believed that adults could not experience neuroplasticity, but contemporary research has debunked this myth, revealing that the brain’s adaptive capacity persists throughout life.

The modern understanding of neuroplasticity is rooted in Donald Hebb’s 1949 theory articulated in his seminal work: The Organization of Behavior.1 Hebb’s principle, often summarized as “cells that fire together wire together,” explains how repeated and persistent stimulation of a postsynaptic cell by a presynaptic cell enhances synaptic efficacy. This principle laid the groundwork for recognizing the brain’s ability to adapt and reorganize, a concept that has profound implications for stroke recovery.

In the context of stroke, neuroplasticity manifests in distinct phases and mechanisms, offering pathways for potential recovery.

The immediate phase occurred in the first 48 hours. Initial stages are marked by cell death and loss of associated cortical pathways. This acute degeneration leads to atrophy in perilesional gray matter and significant structural and functional changes in the contralesional hemisphere. During this period, the brain attempts to utilize secondary neuronal networks to maintain function. After that starts the subacute phase, lasting for some weeks following stroke. In this phase, the recruitment of support cells becomes prominent, transitioning cortical pathways from inhibitory to excitatory. Synaptic plasticity and the formation of new connections are critical during this time, paving the way for potential recovery. Then there is the last subacute phase, weeks to months after stroke. In this period the brain continues to remodel itself through axonal sprouting and further reorganization around the damaged area, emphasizing the ongoing nature of neuroplastic recovery.

Advancements in neuroimaging and neurophysiology have provided tools to measure neuroplastic changes. Several tools are available now to investigate neuroplasticity with different spatial and temporal precision and resolution.

Techniques such as functional magnetic resonance imaging (fMRI), diffusion-weighted imaging (DWI), positron emission tomography (PET) and repetitive transcranial magnetic stimulation (rTMS) offer important insights into brain activity and structural changes.2 Additionally, biological markers are used to gauge neuroplasticity and angiogenesis,3 a process implicated in neurorepair. Some markers are used as promising clinical tools for stroke recovery evaluation in the acute phase (a few days after stroke) as matrix Metalloproteinase 9 (MMP9) and Angiopoietin 2 (Ang2), others find application in the most common post-stroke rehabilitation phase (within 6 months after stroke) like Irisina, Brain-Derived Neurotrophic Factor (BDNF), and Vascular Endothelial Growth Factor (VEGF).

However, not all the processes of structural and functional changes to the brain after stroke have to be considered as a favorable sign for the best recovery, since it is well known that neuroplastic changes can also be maladaptive and negatively affect human function.4

Rehabilitation is undoubtedly recognized to be effective for recovery of function and mobility after stroke, when compared versus no treatment or attention control,5 but not all the strategies show the same results.6 Therefore, we may assume that some interventions are more effective than others in activating neuroplasticity.

Do we have also some evidence that stroke rehabilitation may play a role in enhancing neuroplasticity? In the last years, some papers showed that rehabilitative interventions are able to induce neuroplastic changes in terms of imaging, response to noninvasive transcranial brain stimulations, or concentration of biomarkers. For example, a very recent systematic review on the effect of exercise on BDNF in stroke survivors showed that exercise parameters influence BDNF concentration.7 In particular, high intensity aerobic exercise can increase more than the non-aerobic ones the circulating BDNF concentrations. Another interesting example is offered by findings of another study on functional connectivity changes in the cortical motor network after rTMS.8 This study showed that, in early-stage cerebral stroke patients, rTMS seem to induce functional connectivity changes improving motor function recovery.

Unfortunately, research in this field is still in its primordial phase. Moreover, to date the impact of patient’s age on neuroplasticity is unclear, and appropriate dosage of each rehabilitative active intervention is usually not reported in most of the literature.

We believe that, like a carefully calibrated medication, rehabilitation interventions should be tailored to include the best combination of exercises, with optimal dosage, appropriate frequency, and sufficient duration (Table I).

Table I —ReCipe Table.

Active ingredients	Provider	Modes of delivery	N. sessions	Frequency	Duration	Dose/intensity	
Task-oriented specific training upper limb	PT	I	54	6/week	20’	15 repetitions	
Trunk control training	PT	I	12	6/week	10’	15 repetitions	
High-intensity training for walking	PT	I	50	5/week	30’	Heart rate reserve = 60-80% or ratings of perceived exertion = 15	
PT: physiotherapist; I: individually.

In conclusion, the potential for neuroplasticity in stroke recovery is immense. Despite the complexities and variances in individual cases, the overarching principle remains clear: the brain’s ability to adapt and reorganize offers a promising avenue for rehabilitation. By understanding and harnessing this potential, clinicians and researchers can develop more effective strategies to support stroke patients, ultimately improving their quality of life.

Conflicts of interest: The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript.
==== Refs
References

1 Hebb DO. The Organization of Behavior: A neuropsychological theory. New York: John Wiley & Sons, Inc.; 1949.
2 Christiansen L Siebner HR . Tools to explore neuroplasticity in humans: combining interventional neurophysiology with functional and structural magnetic resonance imaging and spectroscopy. Handb Clin Neurol 2022;184 :105–19. https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=35034728&dopt=Abstract 10.1016/B978-0-12-819410-2.00032-1 35034728
3 Wlodarczyk L Szelenberger R Cichon N Saluk-Bijak J Bijak M Miller E . Biomarkers of angiogenesis and neuroplasticity as promising clinical tools for stroke recovery evaluation. Int J Mol Sci 2021;22 :3949. https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=33920472&dopt=Abstract 10.3390/ijms22083949 33920472
4 Johnson BP Cohen LG . Applied strategies of neuroplasticity. Handb Clin Neurol 2023;196 :599–609. https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=37620093&dopt=Abstract 10.1016/B978-0-323-98817-9.00011-9 37620093
5 Pollock A, Baer G, Campbell P, Choo PL, Forster A, Morris J, et al. Physical rehabilitation approaches for the recovery of function and mobility following stroke. Cochrane Database Syst Rev 2014;2014:CD001920. https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=24756870&dopt=Abstract
6 Scrivener K Dorsch S McCluskey A Schurr K Graham PL Cao Z Bobath therapy is inferior to task-specific training and not superior to other interventions in improving lower limb activities after stroke: a systematic review. J Physiother 2020;66 :225–35. https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=33069609&dopt=Abstract 10.1016/j.jphys.2020.09.008 33069609
7 Ashcroft SK Ironside DD Johnson L Kuys SS Thompson-Butel AG . Effect of exercise on brain-derived neurotrophic factor in stroke survivors: a systematic review and meta-analysis. Stroke 2022;53 :3706–16. https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=36278401&dopt=Abstract 10.1161/STROKEAHA.122.039919 36278401
8 Chen Q Shen W Sun H Zhang H Liu C Chen Z The effect of coupled inhibitory-facilitatory repetitive transcranial magnetic stimulation on shaping early reorganization of the motor network after stroke. Brain Res 2022;1790 :147959. https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=35654120&dopt=Abstract 10.1016/j.brainres.2022.147959 35654120
