Thymosin β4 and brain regeneration: what animal studies say about its role in regeneration, repair and protection

Main article on TB-500

Description of the potential effects of Thymosin β4 (Tβ4) based on the literature. (This is not a product description, disclaimer at the bottom of the page)

Thymosin β4 (also known as Tβ4 or timbetasin) is a powerful therapeutic compound that helps the brain and nervous system recover from damage. Its effects go far beyond protecting brain cells immediately after injury. Animal studies show that it can help with many types of brain-related problems, such as traumatic brain injury (TBI), stroke, and damage caused by alcohol, toxic proteins and diseases such as multiple sclerosis and Alzheimer's disease.

It works by supporting the entire "neurovascular unit," which includes brain cells (neurons), supporting cells (glial), blood vessel cells and the protective barrier around the brain called the blood-brain barrier (BBB). Even if the treatment is started late, such as a day or a few days after the injury, it still helps improve mobility and memory in the animals, even if the extent of brain damage does not significantly decrease. This shows that it mainly helps by restoring and repairing, not just protecting.

Thymosin β4 works in this way by helping new blood vessels and brain cells grow, repairing the protective insulation around nerves and strengthening the brain barrier. At a deeper level, it reduces harmful chemicals in the brain, alleviates inflammation and oxidative stress, and keeps cells alive by enhancing protective proteins such as Bcl-2 and antioxidant enzymes. It also affects microRNAs and growth signals that instruct brain cells to repair themselves. The effects of thymosin β4 depend on the condition being treated, the dose given and the timing of its application. For example, in stroke, too high a dose may not work well, and in some studies of brain injury, earlier or stronger doses produced better results. In addition, in healthy brains, it can cause excessive growth of certain brain-supporting cells, so careful use and testing is important.

Thymosin β4 promotes brain healing after traumatic brain injury (TBI), even when given as a delayed treatment. In a study in rats by Xiong et al (2011), researchers investigated whether thymosin β4 could aid recovery from controlled brain injury [1]. Rats were treated with thymosin β4 (6 mg/kg) one day after injury and then every three days for four consecutive doses. Although the extent of brain damage did not decrease, the loss of nerve cells in the hippocampus decreased, the growth of new blood vessels and brain cells increased, and the development of supporting cells (oligodendrocytes) was promoted. Rats treated with thymosin β4 also performed better in motor tests and memory tasks. This suggests that even with delayed treatment, it stimulates natural brain repair processes, including the growth of neurons and blood vessels.

Earlier and higher doses of thymosin β4 provide stronger protection and promote greater recovery after brain injury. In another experiment, Xiong et al (2012) administered thymosin β4 to rats just 6, 24 and 48 hours after brain injury [2]. Two doses were tested: 6 mg/kg and 30 mg/kg. This improved motor coordination and memory, reduced the extent of brain damage and protected brain cells in the hippocampus. It also increased the formation of new brain cells, especially at the higher dose. These results show that thymosin β4 can act as both a protective and therapeutic agent when administered soon after injury.

Thymosin β4 reduces damage caused by excessive neuronal stimulation in both in vitro and animal models. Popoli et al (2007) studied the effects of thymosin β4 on brain damage caused by excessive neuronal stimulation (a condition called excitotoxicity) [3]. In neurons grown in the laboratory and rat brain tissue sections, it protected against damage caused by glutamate, a chemical that can be toxic in large amounts. In live rats exposed to kainic acid (which mimics excessive brain stimulation), it also reduced neuronal loss. These results suggest that thymosin β4 helps by controlling calcium levels and reducing oxidative and inflammatory stress. Thymosin β4 protects brain cells from alcohol-induced damage. In a study by Yang et al (2010), thymosin β4 was tested on brain support cells (astrocytes) exposed to alcohol for several days [4]. When the cells were pretreated with thymosin β4, they remained alive longer, showed fewer signs of cell death and produced more protective proteins such as Bcl-2. It also reduced markers of oxidative stress and preserved cell structure. This indicates that thymosin β4 helps astrocytes counteract alcohol-related damage and inflammation.

In a mouse model of Alzheimer's disease, thymosin β4 reduces inflammation and amyloid accumulation, although it can activate immune cells in healthy brains. Othman et al (2023) tested thymosin β4 on older mice genetically susceptible to developing Alzheimer's disease (APP/PS1 mice) [5]. When injected with a bacterial toxin (LPS) to mimic infection, these mice showed increased amyloid plaques and disease symptoms. Thymosin β4 (5 mg/kg) prevented the increase in plaques and reduced behavioral symptoms such as weight loss and apathy. However, in healthy mice, it induced excessive growth of some brain immune cells (astrocytes and microglia), suggesting that while it may protect the brain from Alzheimer's disease, it may also over-stimulate immune responses in the normal brain.

Thymosin β4 prevents neuronal death caused by toxic prion peptides by increasing the expression of growth factors and reducing oxidative stress. In a study by Kim et al (2023), nerve cells exposed to a toxic prion peptide (PrP 106-126) were protected by treatment with thymosin β4 [6]. It increased the survival of these cells, reduced oxidative stress and lowered markers of cell death. It also increased the production of brain growth factors, such as NGF and BDNF, and helped maintain their receptors. This suggests that it protects nerve cells by restoring growth signals that are disrupted by toxic proteins. Thymosin β4 maintains the integrity of the blood-brain barrier against damage caused by prion peptides ( ). In a laboratory model using human cerebral vascular cells (hCMEC/D3), Song et al (2020) showed that thymosin β4 helped maintain a tight barrier between brain cells, which is often damaged by harmful prion peptides such as PrP [7]. It increased the levels of protective proteins such as claudin-5 and occludin, stabilized the internal structure of the cell (actin) and improved electrical resistance in the cell layer. It also reduced leakage between cells and maintained the normal shape and connections of the barrier. These actions demonstrate how thymosin β4 helps maintain a strong protective wall of the brain during stress or injury. In addition, it alters the microRNA profiles circulating after brain injury, suggesting a systemic involvement in tissue repair. After severe brain injury in rats, Osei et al (2018) found that thymosin β4 affected small RNA molecules (microRNAs) circulating in the blood [8]. It enhanced protective types such as miR-200a-3p and miR-200b-3p, and reversed the injury-induced decline in miR-194-5p. It also altered the levels of nine other microRNAs involved in inflammation, cell death and tissue repair. These changes suggest that thymosin β4 does not act only locally in the brain, but also triggers broader healing signals throughout the body.

Researchers highlight the broad neuroregenerative potential of thymosin β4 throughout the nervous system. Chopp and Zhang (2015) highlighted that thymosin β4 promotes many processes necessary for brain and nerve regeneration [9]. It helps develop new blood vessels and neurons, repairs axons (nerve fibers) and promotes the formation of oligodendrocytes, cells that help insulate nerves. Interestingly, these effects were observed even when the treatment was started a day or more after the injury. The authors suggest that this may work by affecting microRNAs and using exosomes (tiny signal-carrying molecules) to spread repair signals between cells. Thymosin β4 may reduce neuroinflammation by modulating microglia activity. In a review, Pardon (2018) explained that thymosin β4 is found in large amounts in both neurons and microglia, which are cells similar to immune cells in the brain [10]. During brain inflammation, microglia increase levels of thymosin β4, and studies show that it can reduce harmful inflammatory signals produced by these cells. For this reason, it may be useful in long-term brain disorders, such as Alzheimer's disease, in which ongoing inflammation plays a detrimental role. The review calls for further research to fully understand how and when thymosin β4 can be used.

Thymosin β4 promotes brain regeneration by actively repairing damaged tissues, not just preventing further damage. Morris et al (2012) reviewed several animal studies on stroke, multiple sclerosis and brain injury [11]. They found that thymosin β4 helped the animals recover by growing new brain cells and supporting cells and repairing neural structures, not just by protecting existing tissues during injury. This suggests that it may be more useful in therapies targeting long-term regeneration and recovery. In older rats, thymosin β4 reduces stroke-induced brain damage ( ), although behavioral improvements are inconsistent. In elderly rats that had undergone a stroke, Morris et al (2017) administered thymosin β4 starting 24 hours after the stroke [12]. This significantly reduced the extent of brain damage by more than half. However, the rats did not show improved performance in motor or sensory tests. There was also no noticeable improvement in cell repair or supporting tissue. Interestingly, one type of brain cell activity (astrocytic glial) was associated with better test results regardless of treatment, suggesting that aging brains may respond differently to thymosin β4 therapy.

Low to moderate doses of thymosin β4 improve recovery from stroke, while higher doses may lose efficacy. In a study in rats that had a stroke, Morris et al (2014) tested three doses of thymosin β4, including 2, 12 and 18 mg/kg [13]. Treatment was started 24 hours after stroke and continued every three days for five doses. Only the groups receiving the 2 mg/kg and 12 mg/kg doses showed improvement in brain function from day 14 to day 56. The highest dose (18 mg/kg) did not help, showing that a higher dose is not always better. The best estimated dose was 3.75 mg/kg. Brain damage (lesion size) decreased in the groups receiving the helpful dose, although exact numbers were not given. Thymosin β4 promotes brain repair after injury by activating multiple regenerative mechanisms. Xiong et al. (2012) analyzed several models of brain injury and found that administration of thymosin β4 after injury helped brain recovery in multiple ways [14]. It stimulated the growth of new blood vessels, nerve cells, supporting cells and neural connections. Thymosin β4 also reduced inflammation and cell death. It helped brain stem cells survive and grow, demonstrating that its therapeutic effect is not only due to its known role in controlling cell structure. Ac-SDKP's thymosin β4 fragment promotes neurogenesis and improves memory function. Kim et al (2015) administered a small amount of Ac-SDKP thymosin β4 directly to the hippocampus (a brain area important for memory) in mice [15]. This treatment led to more new brain cells and improved memory in maze tests. These effects were associated with changes in cell growth signals (such as β-catenin and VEGF). When VEGF was blocked, these benefits disappeared, indicating that it is an essential component of Ac-SDKP's action.

In a model of multiple sclerosis, thymosin β4 improves motor function and facilitates neuronal repair. Zhang et al (2009) studied mice with a disease similar to multiple sclerosis [16]. Thymosin β4 was administered every three days, starting from the day the disease was induced. The treated mice moved better, had fewer immune cells attacking the brain and more brain repair cells (oligodendrocytes). Laboratory tests showed that it helped the development and growth of these repair cells, both in live animals and in cell cultures. These results support the role of thymosin β4 in reducing inflammation and promoting brain regeneration. Thymosin β4 peptides protect developing neurons from cell death in early models of brain development. Choi et al (2007) tested thymosin β4-derived peptides in cultured Glial cell neurons ( ) and animal embryos in the laboratory [17]. The peptides blocked cell death in both laboratory cells and developing motor neurons in chick and rat embryos. When thymosin β4 was blocked, more neurons died, showing that thymosin β4 produced by the body helps protect brain cells. This protection was not based on its usual function of managing cell structure, which means it can send separate survival signals to cells.

In neonatal rats suffering from hypoxia, thymosin β4 inhibits excessive activation of brain immune cells. Zhou et al (2015) studied young rats exposed to low oxygen concentrations (hypoxia), which can cause brain damage [18]. Thymosin β4 reduced the levels of harmful immune chemicals (such as TNF-α and IL-1β) in the brain and cultured immune cells. It also raised levels of microRNA-146a, a small molecule that helps control inflammation. This shows that it can alleviate brain inflammation in newborns by activating microRNA-mediated anti-inflammatory signals. Thymosin β4 facilitates the removal of amyloid plaques, reduces brain inflammation and improves memory in Alzheimer's disease models. In a study in a mouse model of Alzheimer's disease (APP/PS1), Wang et al (2021) increased the amount of thymosin β4 in the brain and examined its effects on memory, mood and brain inflammation [19]. It reduced the harmful accumulation of amyloid-β (Aβ), increased the level of insulin-degrading enzyme (IDE) to help remove Aβ, and changed the brain's immune cells (microglia and astrocytes) to a more healing and less harmful state. The mice showed better memory, learning ability and less depression-like behavior. It also improved the health of brain cell connections (synapses). Mechanistically, thymosin β4 blocked both major branches of the inflammatory pathway (NF-κB) by reducing signaling through TLR4 and MyD88. When additional inhibitors were added, they did not enhance its action, showing that this was the main pathway used.

After stroke, thymosin β4 protects the brain by reducing stress-induced neuronal death. Zhang et al. (2019) tested thymosin β4 in rats after temporary blockage of blood flow to the brain (stroke model), followed by reperfusion [20]. Thymosin β4 was administered before blood flow was restored. It helped the rats recover better, reduced the number of dying brain cells (fewer TUNEL-positive cells) and improved the levels of stress-related proteins in the brain. It increased the levels of GRP78 (a protective protein), while decreasing the levels of CHOP and caspase-12 (proteins associated with cell death). These results suggest that thymosin β4 helps brain cells survive by managing cellular stress. Thymosin β4 supports recovery from stroke mainly by promoting tissue repair, rather than by limiting the extent of the initial damage. In another stroke model, Morris et al (2010) administered thymosin β4 to rats, starting the day after stroke and repeating every three days [21]. Although the extent of brain damage did not decrease, the rats performed better on neurological tests over time (starting on day 14 and continuing until day 56). The number of myelinated nerve fibers, new blood vessels and special brain repair cells (OPCs and oligodendrocytes) near the damaged area increased, indicating that it helps repair, not just protect.

After stroke, endogenous production of thymosin β4 increases in both damaged and surrounding brain areas. Vartiainen et al. (1996) showed that after stroke, thymosin β4 mRNA (a sign of gene activity) increased in both the damaged brain area and surrounding areas [22]. It was particularly high in the center of the stroke and moderate in nearby zones and in important brain areas such as the hippocampus. Immune cells (macrophages) were mainly responsible for the increase in the damaged zone, while brain cells also contributed in other areas. This pattern shows that thymosin β4 is naturally involved in the brain's response to damage, including control of inflammation and repair of nerve fibers. Thymosin β4 promotes remyelination in multiple sclerosis by activating regenerative growth pathways. Zhang et al (2016) used two models of central nervous system (CNS) demyelination: one for multiple sclerosis (EAE) and another using a toxin (cuprizone) that removes nerve insulation [23]. Mice given thymosin β4 daily had better neurological outcomes, with more newly formed and mature brain support cells (oligodendrocytes) and less nerve damage. In laboratory tests, it enhanced EGFR signaling, a key growth pathway. When EGFR was blocked, it could not help cells grow, proving that this signaling pathway is essential to its function in promoting remyelination.

Thymosin β4 enhances brain regeneration after stroke by stimulating neurogenesis and synaptic plasticity. In a rat model of stroke caused by arterial blockage (embolic MCAo), Morris et al (2010) studied how thymosin β4 enhances brain regeneration [24]. Rats treated with thymosin β4 showed better improvement in behavioral tests and higher levels of DCX, a marker of new nerve cells, in areas near the stroke and in the brain stem cell zone (SVZ). Researchers believe it works by promoting the movement of these brain stem cells and their transformation into mature nerve cells. It also appears to promote the growth of new blood vessels, which aids brain healing and function. In addition, it offers age-dependent benefits after stroke, with different effects in young and older rats. Morris et al (2018) looked at how age affects the response to thymosin β4 after stroke [25]. In young rats, low to moderate doses (2 or 12 mg/kg) led to 24-36% improved coordination and movement, although the extent of brain damage remained the same. In brain tissue, more new repair cells (OPCs), better insulation of nerve fibers (more MBP), and reduced inflammation were observed due to microRNAs such as miR-146a and miR-200a, which help activate healing signals such as AKT and reduce cell death (p53 down). In older rats, thymosin β4 did not improve mobility, but halved stroke damage and slightly improved the blood-brain barrier (BBB), indicating a protective effect on brain tissues rather than motor ability.

Thymosin β4 improves motor function and reduces axonal damage after spinal cord injury. In a spinal cord injury (SCI) model, Cheng et al (2014) administered thymosin β4 to rats soon after injury and then again several days later [26]. Rats treated with thymosin β4 moved better, had more healthy nerve insulator cells (57.8% more MBP) and showed less inflammation, with fewer activated immune cells (ED1⁺ ) and lower levels of harmful inflammatory signals. The amount of IL-10, a molecule that promotes healing, increased. The size of tissue defects in the spinal cord also decreased, indicating that thymosin β4 helped reduce secondary damage through better cell survival, reduced scarring and control of inflammation. It also protects neuron-like cells from damage caused by oxygen and glucose deficiency. In PC12 cells grown in the lab (similar to brain cells), Ji et al. (2018) simulated damage by removing oxygen and glucose and then re-exposing them (OGD/R) [27]. Pre-treating cells with thymosin β4 helped them survive better, reduced markers of oxidative damage (LDH, MDA) and enhanced antioxidant enzymes (GSH-Px, SOD). It also prevented excessive cell death by maintaining high levels of Bcl-2 and reducing harmful changes. It stopped harmful excessive recycling in the cell (autophagy) by balancing proteins such as Atg5, LC3 and p62. In conclusion, thymosin β4 helped cells resist stress by promoting antioxidant defense and blocking self-destructive processes.

Applications

All studies to date suggest that thymosin β4 is a drug with a number of beneficial effects that support the brain's healing process. It helps rebuild small blood vessels and strengthens the brain's natural protective barrier. It also stimulates the growth of new brain cells and supporting cells and helps repair the protective coating around the nerves. It reduces harmful brain overactivity, reduces oxidative stress and alleviates inflammation. In addition, it activates specific genes and small molecules called microRNAs that promote long-term regeneration.

These combined actions explain why thymosin β4 can improve brain function even when administered a few days after injury. Its benefits appear to be particularly important in the later stages of recovery, when tissue reconstruction is more important than simply protecting against immediate damage. However, not all studies have shown the same level of improvement, especially in older animals. Moreover, higher doses of thymosin β4 are not always better; some results show that a moderate dose works best. In healthy brains, it may even over-activate some supporting cells, something to watch out for.

To use thymosin β4 safely and effectively in humans, researchers need to determine the best dose and timing of administration. They also need to improve the way it is administered, such as using targeted or slow-release forms. Researchers could use blood markers such as microRNA or brain imaging to select patients most likely to benefit. It could also work better in combination with other treatments, such as physical rehabilitation, anti-inflammatory drugs or stem cell therapies. If these factors are properly studied in future clinical trials, it could become a valuable treatment that helps the brain heal after different types of injury by activating the body's own repair systems.

Disclaimer

This article was written for educational purposes and is intended to raise awareness of the substance under discussion. It is important to note that the article is about the substance in general - it is not a description of a specific product (chemical reagent). We do not suggest using chemical reagents on humans - this is prohibited by law. For a product to be used for treatment, it must be registered as a drug. The information in the text is based on available scientific research and is not intended to serve as medical advice or promote self-medication. The reader should consult any health and treatment decisions with a qualified health professional.

References

1. Xiong, Y., Mahmood, A., Meng, Y., Zhang, Y., Zhang, Z. G., Morris, D. C., and Chopp, M. (2011). Treatment of traumatic brain injury with thymosin β4 in rats. Journal of Neurosurgery, 114(1), 102-115. https://doi.org/10.3171/2010.4.JNS10118https://pubmed.ncbi.nlm.nih.gov/20486893/ 
2. Xiong, Y., Zhang, Y., Mahmood, A., Meng, Y., Zhang, Z. G., Morris, D. C., and Chopp, M. (2012). Neuroprotective and neurorestorative effects of thymosin β4 treatment initiated 6 hours after traumatic brain injury in rats. Journal of Neurosurgery, 116(5), 1081-1092. https://doi.org/10.3171/2012.1.JNS111729 https://pubmed.ncbi.nlm.nih.gov/22324420/
3. Popoli, P., Pepponi, R., Martire, A., Armida, M., Pèzzola, A., Galluzzo, M., Domenici, M. R., Potenza, R. L., Tebano, M. T., Mollinari, C., Merlo, D., & Garaci, E. (2007). Neuroprotective effects of thymosin beta4 in experimental models of excitotoxicity. Annals of the New York Academy of Sciences, 1112, 219-224. https://doi.org/10.1196/annals.1415.033https://pubmed.ncbi.nlm.nih.gov/17947590/ 
4. Yang, H., Cui, G. B., Jiao, X. Y., Wang, J., Ju, G., & You, S. W. (2010). Thymosin beta4 attenuates ethanol-induced neurotoxicity in cultured cerebral cortical astrocytes by inhibiting apoptosis. Cellular and molecular neurobiology, 30(1), 149-160. https://doi.org/10.1007/s10571-009-9439-6 https://pubmed.ncbi.nlm.nih.gov/19688260/
5. Othman, O., Marshall, H., Masterson, M., Winlow, P., Gibson, G., Ding, Y., and Pardon, M.-C. (2023). Thymosin beta 4 prevents lipopolysaccharide-induced systemic platelet burden in middle-aged APP/PS1 mice. International Immunopharmacology, 117, 109951. https://doi.org/10.1016/j.intimp.2023.109951 https://pubmed.ncbi.nlm.nih.gov/36878045/
6. Kim, S., Choi, J., and Kwon, J. (2023). Thymosin beta 4 protects hippocampal neuronal cells from PrP (106-126) via neurotrophic factor signaling. Molecules, 28(9), 3920. https://doi.org/10.3390/molecules28093920https://pubmed.ncbi.nlm.nih.gov/37175330/ 
7. Song, K., Han, H.-J., Kim, S., and Kwon, J. (2020). Thymosin beta 4 attenuates PrP(106-126)-induced human brain endothelial cell dysfunction. European Journal of Pharmacology, 869, 172891. https://doi.org/10.1016/j.ejphar.2019.172891https://pubmed.ncbi.nlm.nih.gov/31877278/
8. Osei, J., Kelly, W., Toffolo, K., Donahue, K., Levy, B., Bard, J., Wang, J., Levy, E., Nowak, N., and Poulsen, D. (2018). Thymosin beta 4 induces significant changes in plasma miRNA profile after severe brain injury in a rat model of lateral fluid injury. Expert Opinion on Biological Therapy, 18(sup1), 159-164. https://doi.org/10.1080/14712598.2018.1484102https://pubmed.ncbi.nlm.nih.gov/29873258/ 
9. Chopp, M. and Zhang, Z. G. (2015). Thymosin β4 as a regenerative/restorative therapy for neurological injury and neurodegenerative diseases. Expert Opinion on Biological Therapy, 15(Suppl 1), S9-S12. https://doi.org/10.1517/14712598.2015.1005596 https://pubmed.ncbi.nlm.nih.gov/25613458/
10. Pardon, M. C. (2018). Anti-inflammatory potential of thymosin β4 in the central nervous system: implications for progressive neurodegenerative diseases. Expert Opinion on Biological Therapy, 18(Suppl 1), 165-169. https://doi.org/10.1080/14712598.2018.1486817 https://pubmed.ncbi.nlm.nih.gov/30063850/
11. Morris, D. C., Zhang, Z. G., Zhang, J., Xiong, Y., Zhang, L., and Chopp, M. (2012). Treatment of neurologic injury with thymosin β4. Annals of the New York Academy of Sciences, 1269(1), 110-116. https://doi.org/10.1111/j.1749-6632.2012.06651.x https://pubmed.ncbi.nlm.nih.gov/23045978/
12. Morris, D. C., Cheung, W. L., Loi, R., Zhang, T., Lu, M., Zhang, Z. G., and Chopp, M. (2017). Thymosin β4 in the treatment of acute stroke in aged rats. Neuroscience Letters, 659, 7-13. https://doi.org/10.1016/j.neulet.2017.08.064 https://pubmed.ncbi.nlm.nih.gov/28864242/
13. Morris, D. C., Cui, Y., Cheung, W. L., Lu, M., Zhang, L., Zhang, Z. G., and Chopp, M. (2014). A dose-response study on the use of thymosin β4 in the treatment of acute stroke. Journal of the Neurological Sciences, 345(1-2), 61-67. https://doi.org/10.1016/j.jns.2014.07.006 https://pubmed.ncbi.nlm.nih.gov/25060418/
14. Xiong, Y., Mahmood, A., Meng, Y., Zhang, Y., Zhang, Z. G., Morris, D. C., and Chopp, M. (2012). Neuroprotective and neurorestorative effects of thymosin β4 treatment after experimental brain injury. Annals of the New York Academy of Sciences, 1270, 51-58. https://doi.org/10.1111/j.1749-6632.2012.06683.x https://pubmed.ncbi.nlm.nih.gov/23050817/
15. Kim, D. H., Moon, E. Y., Yi, J. H., Lee, H. E., Park, S. J., Ryu, Y. K., Kim, H. C., Lee, S., and Ryu, J. H. (2015). Thymosin β4 peptide fragment increases neurogenesis in the hippocampus and facilitates spatial memory. Neuroscience, 310, 51-62. https://doi.org/10.1016/j.neuroscience.2015.09.017 https://pubmed.ncbi.nlm.nih.gov/26363149/
16. Zhang, J., Zhang, Z. G., Morris, D., Li, Y., Roberts, C., Elias, S. B., and Chopp, M. (2009). Neurological function recovery after thymosin beta4 treatment in mice with experimental autoencephalomyelitis. Neuroscience, 164(4), 1887-1893. https://doi.org/10.1016/j.neuroscience.2009.09.054 https://pubmed.ncbi.nlm.nih.gov/19782721/
17. Choi, S. Y., Noh, M. R., Kim, D. K., Sun, W. and Kim, H. (2007). Neuroprotective function of thymosin beta and its downstream peptides in programmed cell death of chick and rat neurons. Biochemical and Biophysical Research Communications, 362(3), 587-593. https://doi.org/10.1016/j.bbrc.2007.08.031   https://pubmed.ncbi.nlm.nih.gov/17716628/ 
18. Zhou, T., Huang, Y., Song, J. and Ma, Q. (2015). Thymosin β4 inhibits microglia activation through microRNA 146a in newborn rats after hypoxic injury. Neuroreport, 26(17), 1032-1038. https://doi.org/10.1097/WNR.0000000000000463 https://pubmed.ncbi.nlm.nih.gov/26457369/
19. Wang, M., Feng, L.-R., Li, Z.-L., Ma, K.-G., Chang, K.-W., Chen, X.-L., ... & Qian, Y.-H. (2021). Thymosin β4 reverses glial cell phenotypic polarization and cognitive impairment by negatively regulating the NF-κB signaling axis in APP/PS1 mice. Journal of Neuroinflammation, 18(1), 146. https://doi.org/10.1186/s12974-021-02166-3 https://pubmed.ncbi.nlm.nih.gov/34183019/
20. Zhang, Z., Liu, S. and Huang, S. (2019). Effects of thymosin β4 on neuronal apoptosis in a rat model of ischemia-reperfusion-induced brain injury. Molecular Medicine Reports, 20(5), 4186-4192. https://doi.org/10.3892/mmr.2019.10683 https://pubmed.ncbi.nlm.nih.gov/31545437/
21. Morris, D. C., Chopp, M., Zhang, L., Lu, M., and Zhang, Z. G. (2010). Thymosin beta4 improves functional neurological outcomes in a rat model of embolic stroke. Neuroscience, 169(2), 674-682. https://doi.org/10.1016/j.neuroscience.2010.05.017https://pubmed.ncbi.nlm.nih.gov/20627173/ 
22. Vartiainen, N., Pyykönen, I., Hökfelt, T. and Koistinaho, J. (1996). Induction of thymosin beta(4) mRNA after focal cerebral ischemia. Neuroreport, 7(10), 1613-1616. https://doi.org/10.1097/00001756-199607080-00017 https://pubmed.ncbi.nlm.nih.gov/8904767/
23. Zhang, J., Zhang, Z. G., Li, Y., Lu, M., Zhang, Y., Elias, S. B., & Chopp, M. (2016). Thymosin beta4 promotes oligodendrogenesis in the demyelinating central nervous system. Neurobiology of Disease, 88, 85-95. https://doi.org/10.1016/j.nbd.2016.01.010https://pubmed.ncbi.nlm.nih.gov/26805386/ 
24. Morris, D. C., Chopp, M., Zhang, L., & Zhang, Z. G. (2010). Thymosin beta4: a candidate for stroke treatment? Annals of the New York Academy of Sciences, 1194, 112–117. https://doi.org/10.1111/j.1749-6632.2010.05469.x https://pmc.ncbi.nlm.nih.gov/articles/PMC3146053/
25. Morris, D. C., Zhang, Z. G. and Chopp, M. (2018). Thymosin β4 in the treatment of acute stroke: neurorestorative or neuroprotective? Expert opinion on biological therapy, 18(sup1), 149–158. https://doi.org/10.1080/14712598.2018.1484100 https://pmc.ncbi.nlm.nih.gov/articles/PMC6481613/
26. Cheng, P., Kuang, F., Zhang, H., Ju, G. and Wang, J. (2014). Beneficial effects of thymosin β4 on spinal cord injury in rats. Neuropharmacology, 85, 408-416. https://doi.org/10.1016/j.neuropharm.2014.06.004 https://pubmed.ncbi.nlm.nih.gov/24937047/
27. Ji, H., Xu, L., Wang, Z., Fan, X., and Wu, L. (2018). Effects of thymosin β4 on hypoxia and reoxygenation-induced damage. International Journal of Molecular Medicine, 41(3), 1749-1755. https://doi.org/10.3892/ijmm.2018.3369 https://pubmed.ncbi.nlm.nih.gov/29328391/