The leading cause of adult disability and death all over the world is stroke, since the abrupt termination of brain function occurs due to the interruption of a blood supply. The following damage to neurons and tissue loss in the brain had been considered to be irreparable processes for many years.
This article discusses the fundamental biology of neurogenesis after stroke (the brain’s innate response to stroke), a mix of treatment approaches with an eye toward enhancing neurogenesis for the reestablishment of function.
The Biology of Neurogenesis
Therapy with a stem cell after a stroke is a promising notion. The two regions of the brain where neurogenesis takes place in adults are mostly found in the subventricular zone (SVZ) surrounding the lateral ventricles, as well as the subgranular zone (SGZ) of the hippocampal dentate gyrus.
After a stroke, the mechanisms for self-healing of the brain encompass a neurogenic process upregulation, although they are mostly unable to support significant functional recovery. The understanding of how to amplify and direct such processes is one of the key goals of stroke research.
Endogenous Neurogenic Response to Stroke
Stroke elicits a spontaneous but partial neurogenic response. Approximately 795,000 deaths are caused by strokes each year in the US. The ischemic insult activates NSCs in the SVZ and SGZ for increased proliferation and migration of NPCs towards the injury site.
Cytokines, growth factors (such as brain-derived neurotrophic factors or BDNF), and extracellular matrix components are some of the factors that affect this response.
Yet several obstacles mitigate the effectiveness of this natural response. These areas’ comprehensive microenvironment post stroke is hostile to new neurons, accompanied by inflammation and oxidative stress, as well as poor survival of new neurons and failure to integrate into functional networks.
Pharmacological Strategies
Many pharmacological agents have been demonstrated to promote neurogenesis after stroke in the recovery phase. These include:
- Growth Factors: Movements onto growth factors, including BDNF, VEGF, and FGF-2, have contributed to the NSCs’ proliferation and differentiation.
- Neuroprotective Medications: Neurogenic effects of medications such as statins, erythropoietin, and selective serotonin reuptake inhibitors (SSRIs) have been demonstrated.
- Small Molecules: Molecules and compounds targeting major signaling cascades like Wnt/β-Catenin and Notch have been explored for their role in neural repair.
Pharmacological approaches hold considerable promise due to their non-invasive nature and low potential for learning bias, and are as of yet to be fully explored in terms of dosage, timing, and the side effects of these treatments.
Cell‑Based Therapies
Stem Cell Transplantation is one of the hopes in neuroregeneration after cerebrovascular accidents. Cell Types Various types of cells have been studied, including:
- MDSCs are derived from bone marrow, adipose tissue, or umbilical cord and secrete trophic factors that facilitate the intrinsic repair mechanisms while suppressing inflammation.
- Neural Stem Cells (NSCs), the cells that would give rise to neurons and glial cells, and are capable of migrating to the site of injury, integrating, and changing their function, have been found.
- iPSCs provide a potential for patient-specific medicine, in particular, since it is feasible to generate patient-specific neural progenitors with only a little risk of being rejected by the patient’s immune system.
Despite that, preclinical studies have shown functional improvement in the animal models, clinical translation is in its early stage. Challenges include preservation of cell differentiation, cell viability, and non-tumourigenicity.
Biomaterials and Tissue Engineering
Biomaterials and tissue engineering techniques attempt to build environments conducive to the creation of neurons and brain repair. These include:
- Hydrogels and Scaffolds: Injectable hydrogels with or without growth factors and cells could be used to bridge the defect tissue and serve as the matrix for the cells to migrate and differentiate.
- Nanoparticles: Nanoparticles can be designed to deliver drugs/genetic material directly to neurogenic regions or damaged tissue, allowing precise therapeutic targeting.
- 3D-Bioprinting: The 3D-bioprinting technology is promising to generate biomimetic brain tissue in order to stimulate the growth and fusion of neurons.
The association of biomaterials with stem cells or drugs also causes a synthetic effect, resulting in increased efficacy of neuroregenerative therapies in establishments such as Swiss Medica.
Lifestyle and Rehabilitation Interventions
Non-pharmacological strategies also greatly contribute to promoting neurogenesis after stroke. These include:
- Aerobic activity has been found to enhance neurogenesis in the hippocampus and improve cognitive function among stroke patients.
- An environment that is motivating with social interaction, cognitive tasks, and sensory inputs enhances neuronal plasticity and neurogenesis.
- Intensive therapy traps the neural plasticity and might assist in the incorporation of new neurons into the working circuits.
Emerging Approaches
New breakthrough technologies and discoveries in science are broadening the horizon of neurogenesis-based stroke rehabilitation.
- Gene Therapy: Spanning neurogenic pathways or stemming down the inhibitory prompts in the post-stroke brain is possible by targeted gene delivery.
- Exosome Therapy: MicroRNAs and proteins that cause neurogenesis and inhibit inflammation can be found in the exosomes released from the stem cells.
- Optogenetics and Neuromodulation: Such instruments, as transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS), are being examined with regard to their potential to impact the neural circuits as well as subsequent plasticity.
- Artificial Intelligence and Biomarker Discovery: Machine learning gives a projection of patient-specific responses to therapy and new biomarkers that enable monitoring neurogenesis and recovery.
These exploding strategies are a subject of research; however, they can alter the paradigm of the post-stroke treatment in the future.
Final Thoughts
Neurogenesis offers a bright horizon of stroke rehabilitation with the repair of the brain, which was previously considered impossible.
There are many ways of improving the spontaneous, endogenous response post stroke, from pharmacological interventions to cell-based alternatives, biomaterials, and including lifestyle changes.
More research, clinical studies, and technology will be inevitable for the conversion of these findings to meaningful therapies that will result in better delivery and quality of life for stroke victims in the world.
