Neuroplasticity refers to the nervous system's ability to adapt and reorganize its structure, functions, and connections in response to stimuli. After a stroke, several mechanisms of neural plasticity can be activated, which may lead to significant recovery. A deeper understanding of this plastic remodeling is essential for developing more effective strategies for stroke rehabilitation.

At Ace Therapeutics, we leverage non-invasive imaging techniques such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) to help clients uncover the mechanisms of neuroplasticity for stroke rehabilitation. Furthermore, we collaborate with clients to develop therapies that enhance functional recovery by modulating neuroplasticity.

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What Is Neuroplasticity?

Neuroplasticity, or neural plasticity or brain plasticity, is the brain's remarkable ability to adapt and change. The term "neuro" refers to neurons, the nerve cells that form the foundation of the brain and nervous system, while "plasticity" signifies the capacity for change.

Neuroplasticity refers to the brain's intrinsic ability to make adaptations and reorganize its structure and function in response to stimuli and injuries, including environmental changes, learning experiences, developmental processes, and the consequences of stroke. This inherent property is critical to the brain's ability to adapt and recover from such injuries.

Fig. 1 Mechanisms of neuroplasticity in healthy individuals. (Marín-Medina, et al., 2024)

Neuroplasticity After Stroke

After a stroke, the ischemic insult causes massive disruption in the entire elaborate brain of the target. And it turns out that the healthy parts of the brain surrounding the damaged tissue can rewire to assume new roles. This extraordinary capacity for rewiring and reorganisation is called neuroplasticity. It involves inter-hemispheric lateralisation, the generation of new associations by cortical regions in the damaged region, and reorganising maps of representation.

The Mechanisms of Neuroplasticity After Stroke

After a stroke, neuroplasticity operates through three primary mechanisms that facilitate the reorganization of neural connections, particularly within the first 3–6 months.

• Increased functional activity: Enhanced activity in the somatosensory system on the side of the brain opposite the infarction and recruitment of distant cortical regions connected to the affected area.
• Structural integrity improvement: Strengthening of the corticospinal tract's structural integrity on the same side as the infarction.
• Restoration of connectivity: Recovery of interhemispheric functional connectivity and the sensorimotor cortex network across both sides of the brain.

These mechanisms collectively reallocate functions from damaged areas, promoting recovery.

Fig. 2 Neuroplasticity after stroke. (Marín-Medina, et al., 2024)

Neuroplasticity-Based Interventions in Stroke Recovery

The brain's limited capacity for repair has led to the development of new strategies to enhance brain plasticity. These methods aim either at better brain remodeling and repair, or at building neural bypasses to stop the brain from getting damaged.

Noninvasive Brain Stimulation

Neuroinvasive brain stimulation such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) can potentially enhance neuroplasticity during stroke rehabilitation to improve motor and cognitive function. rTMS is a neurostimulator and neuromodulator that adjusts the stimulation thresholds of the cortical tissue; tDCS is more of a neuromodulator, modulating membrane potential of the neural cells. Both methods mutate brain neurotransmitters such as -aminobutyric acid, glutamate, dopamine and serotonin, and in turn tame genes involved in neuroplasticity, such as c-fos and brain-derived neurotrophic factor.

Fig. 3 Brain stimulation to promote stroke recovery. (Su, et al., 2020)

Constraint-Induced Movement Therapy (CIMT)

CIMT is now a promising technique for increasing neuroplasticity in stroke patients, and enabling motor recovery. We don't know the exact mechanisms, but CIMT was found to cause structural neuroplasticity in the contralesional hemisphere and bihemispheric functional neuroplasticity. They also have reported brain changes due to CIMT: increased dendritic plasticity in both the ipsilateral and contralateral sensorimotor areas and growth factor expression. All these points indicate that CIMT can drive neuroplastic changes that facilitate motor repair, but more studies are required to decipher the mechanism.

Brain-Machine Interface (BMI)

BMI is now a promising assessment for motor rehabilitation, particularly in patients with minimal or no residual function. Recently published articles point to the potency of BMI technologies in modulating neuroplasticity and motor healing following stroke. Through the use of the brain's own plasticity, BMI helps to reshape and rewire neural circuits, which results in improved motor control. Such interfaces link the brain directly to external machines that patients can manipulate with neural signals.

Brain-Computer Interface (BCI)

BCI, similar to BMI, has gained significant attention for their role in stroke rehabilitation. BCI allows patients to interact with external devices or virtual environments using brain activity, particularly through motor imagery tasks. By decoding and translating neural signals from these tasks, BCI enabled control of virtual objects or prosthetic devices. This intervention enhances motor function and stimulates neuroplastic changes in the brain, leading to improved motor performance.

Pharmacological Modulators of Neural Plasticity

Recent experimental animal research has identified several promising approaches to promote functional recovery after stroke by stimulating neural plasticity.

Cell-Based Therapy

Cell therapy involves the transplantation of stem cells or neural precursor cells, presenting significant potential for promoting the regeneration and repair of damaged neural tissue. By introducing these cells into the affected areas, cell therapy aims to enhance the brain's innate regenerative capabilities and facilitate neuroplastic changes contributing to improved motor function.

Fig. 4 Cell transplantation to promote stroke recovery. (Su, et al., 2020)

1. Marín-Medina, D. S., et al. (2024). New approaches to recovery after stroke. Neurological sciences, 45(1), 55-63.
2. Su, F., & Xu, W. (2020). Enhancing brain plasticity to promote stroke recovery. Frontiers in neurology, 11, 554089.