{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T07:58:12Z","timestamp":1782979092960,"version":"3.54.5"},"reference-count":27,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T00:00:00Z","timestamp":1635465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Chronic traumatic brain injury (TBI) can cause permanent disability and thereby negatively affect patients, families, and society. Currently, there is no effective treatment for patients with chronic TBI. One possible option is granulocyte colony-stimulating factor (G-CSF), which has potential neuroregenerative and neuroprotective effects through its ability to mobilize hematopoietic stem cells and increase neurogenic growth factor levels. Previous studies have shown that G-CSF administration is safe for patients with neurological diseases such as stroke and dementia. The present study aimed to explore the safety and efficacy of G-CSF use in patients with chronic TBI. Methods: 38 patients with chronic TBI were administered 3-day rounds of G-CSF (10 \u03bcg\/kg per day) once a month for 6 months. These patients were clinically evaluated using the modified Rankin scale (mRS) and Karnofsky Performance Score (KPS). Laboratory measures of the leucocyte counts and differential count percentage were also assessed. Results: At the 6-month follow-up, further assessment showed that patients tolerated the treatment well with only mild and transient side effects being observed. Further clinical evaluation showed significant improvements in mRS and KPS after G-CSF treatment. Laboratory results also confirmed the action of the medication, with increased leukocytosis and band forms. Conclusions: The results suggest that 6-month chronic G-CSF treatment is safe for patients with chronic TBI and may provide clinical benefits and neurological improvements. The adverse effects of the treatment, however, are transient and usually tolerable. Thus, these preliminary findings suggest that future clinical trials of G-CSF use in patients with chronic TBI are warranted.<\/jats:p>","DOI":"10.3390\/brainsci11111441","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T11:47:38Z","timestamp":1635767258000},"page":"1441","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Granulocyte Colony-Stimulating Factor for Treatment of Patients with Chronic Traumatic Brain Injury: A Preliminary Pre-Post Study"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5717-8104","authenticated-orcid":false,"given":"Tsung-Lang","family":"Chiu","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Hualien Tzu Chi Hospital\/Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Jung","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Hualien Tzu Chi Hospital\/Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tze-Wei","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Hualien Tzu Chi Hospital\/Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinn-Zong","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Hualien Tzu Chi Hospital\/Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6611-9440","authenticated-orcid":false,"given":"Sheng-Tzung","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Hualien Tzu Chi Hospital\/Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"640","DOI":"10.3389\/fneur.2018.00640","article-title":"Multi-Center Pre-clinical Consortia to Enhance Translation of Therapies and Biomarkers for Traumatic Brain Injury: Operation Brain Trauma Therapy and Beyond","volume":"9","author":"Kochanek","year":"2018","journal-title":"Front. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1089\/neu.2013.3106","article-title":"Granulocyte-macrophage colony-stimulating factor is neuroprotective in experimental traumatic brain injury","volume":"31","author":"Shultz","year":"2014","journal-title":"J. Neurotrauma"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1172\/JCI23559","article-title":"The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis","volume":"115","author":"Schneider","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"48","DOI":"10.3389\/fcell.2015.00048","article-title":"The Granulocyte-colony stimulating factor has a dual role in neuronal and vascular plasticity","volume":"3","author":"Wallner","year":"2015","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1089\/neu.2012.2650","article-title":"Inflammatory consequences in a rodent model of mild traumatic brain injury","volume":"30","author":"Rea","year":"2013","journal-title":"J. Neurotrauma"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.nec.2016.06.002","article-title":"Pathophysiology of Traumatic Brain Injury","volume":"27","author":"McGinn","year":"2016","journal-title":"Neurosurg. Clin. N. Am."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.expneurol.2006.12.001","article-title":"Hematopoietic growth factors pass through the blood\u2013brain barrier in intact rats","volume":"204","author":"Zhao","year":"2007","journal-title":"Exp. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.3727\/096368914X678562","article-title":"Intracerebral implantation of autologous peripheral blood stem cells in stroke patients: A randomized phase II study","volume":"23","author":"Chen","year":"2014","journal-title":"Cell Transplant."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/s12975-015-0430-x","article-title":"Translating G-CSF as an Adjunct Therapy to Stem Cell Transplantation for Stroke","volume":"6","author":"Borlongan","year":"2015","journal-title":"Transl. Stroke Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1503\/cmaj.051322","article-title":"Granulocyte colony-stimulating factor for acute ischemic stroke: A randomized controlled trial","volume":"174","author":"Shyu","year":"2006","journal-title":"Can. Med. Assoc. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1161\/01.STR.0000258355.23810.c6","article-title":"Outcomes validity and reliability of the modified Rankin scale: Implications for stroke clinical trials: A literature review and synthesis","volume":"38","author":"Banks","year":"2007","journal-title":"Stroke"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1200\/JCO.1984.2.3.187","article-title":"Karnofsky performance status revisited: Reliability, validity, and guidelines","volume":"2","author":"Schag","year":"1984","journal-title":"J. Clin. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Fl\u00f6el, A., Warnecke, T., Duning, T., Lating, Y., Uhlenbrock, J., Schneider, A., Vogt, G., Laage, R., Koch, W., and Knecht, S. (2011). Granulocyte-colony stimulating factor (G-CSF) in stroke patients with concomitant vascular disease\u2014A randomized controlled trial. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0019767"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"843","DOI":"10.3233\/JAD-2012-120196","article-title":"Pilot study of granulocyte-colony stimulating factor for treatment of Alzheimer\u2019s disease","volume":"31","author":"Cimino","year":"2012","journal-title":"J. Alzheimers Dis."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Sprigg, N., O\u2019Connor, R., Woodhouse, L., Krishnan, K., England, T.J., Connell, L.A., Walker, M.F., and Bath, P.M. (2016). Granulocyte Colony Stimulating Factor and Physiotherapy after Stroke: Results of a Feasibility Randomised Controlled Trial: Stem Cell Trial of Recovery EnhanceMent after Stroke-3 (STEMS-3 ISRCTN16714730). PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0161359"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Duning, T., Schiffbauer, H., Warnecke, T., Mohammadi, S., Fl\u00f6el, A., Kolpatzik, K., Kugel, H., Schneider, A., Knecht, S., and Deppe, M. (2011). G-CSF prevents the progression of structural disintegration of white matter tracts in amyotrophic lateral sclerosis: A pilot trial. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017770"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1097\/WNR.0000000000001397","article-title":"Different changes in granulocyte-colony stimulating factor and its correlation with inflammatory biomarkers in patients after traumatic brain injury","volume":"31","author":"Huang","year":"2020","journal-title":"NeuroReport"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"147000","DOI":"10.1016\/j.brainres.2020.147000","article-title":"The contribution of stem cell factor and granulocyte colony-stimulating factor in reducing neurodegeneration and promoting neurostructure network reorganization after traumatic brain injury","volume":"1746","author":"He","year":"2020","journal-title":"Brain Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1089\/neu.2016.4589","article-title":"Pumping the Brakes: Neurotrophic Factors for the Prevention of Cognitive Impairment and Dementia after Traumatic Brain Injury","volume":"34","author":"Corrigan","year":"2017","journal-title":"J. Neurotrauma"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"113335","DOI":"10.1016\/j.expneurol.2020.113335","article-title":"Long-term beneficial effects of hematopoietic growth factors on brain repair in the chronic phase of severe traumatic brain injury","volume":"330","author":"Qiu","year":"2020","journal-title":"Exp. Neurol."},{"key":"ref_21","first-page":"415","article-title":"Granulocyte-colony stimulating factor promotes brain repair following traumatic brain injury by recruitment of microglia and increasing neurotrophic factor expression","volume":"34","author":"Song","year":"2016","journal-title":"Restor. Neurol. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1007\/s10072-011-0608-2","article-title":"Bone marrow mesenchymal stem cells can be mobilized into peripheral blood by G-CSF in vivo and integrate into traumatically injured cerebral tissue","volume":"32","author":"Deng","year":"2011","journal-title":"Neurol. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"531","DOI":"10.3727\/096368914X678337","article-title":"Mannitol-enhanced delivery of stem cells and their growth factors across the blood\u2013brain barrier","volume":"23","author":"Sanberg","year":"2014","journal-title":"Cell Transplant."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.bbr.2013.11.008","article-title":"Enhancement in cognitive function recovery by granulocyte-colony stimulating factor in a rodent model of traumatic brain injury","volume":"259","author":"Sikoglu","year":"2014","journal-title":"Behav. Brain Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2274","DOI":"10.1097\/01.CCM.0000145998.11686.ED","article-title":"Effect of granulocyte colony-stimulating factor on functional and histopathologic outcome after traumatic brain injury in mice","volume":"32","author":"Sheibani","year":"2004","journal-title":"Crit. Care Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/3-211-30714-1_31","article-title":"Granulocyte colony-stimulating factor does not affect contusion size, brain edema or cerebrospinal fluid glutamate concentrations in rats following controlled cortical impact","volume":"96","author":"Sakowitz","year":"2006","journal-title":"Acta Neurochir. Suppl."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.3171\/2017.7.JNS17878","article-title":"Brain repair by hematopoietic growth factors in the subacute phase of traumatic brain injury","volume":"129","author":"Toshkezi","year":"2018","journal-title":"J. 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