The combined effect of granulocyte-colony stimulating factor (G-CSF) treatment and exercise in rats with spinal cord injury

Transplantation of neural stem cells (NSCs) is a potential strategy for the treatment of spinal cord transection (SCT). Here we investigated whether transplanted NSCs would improve motor function of rats with SCT and explored the underlying mechanism. First, the rats were divided into sham, SCT, and NSC groups. Rats in the SCT and NSC groups were all subjected to SCT in T10, and were administered with media and NSC transplantation into the lesion site, respectively. Immunohistochemistry was used to label Nestin-, TUNEL-, and NeuN-positive cells and reveal the expression and location of type I insulin-like growth factor receptor (IGF-1 R). Locomotor function of hind limbs was assessed by Basso, Beattie, Bresnahan (BBB) score and inclined plane test. The conduction velocity and amplitude of spinal nerve fibers were measured by electrophysiology and the anatomical changes were measured using magnetic resonance imaging. Moreover, expression of IGF-1 R was determined by real-time polymerase chain reaction and Western blotting. The results showed that NSCs could survive and differentiate into neurons in vitro and in vivo. SCT-induced deficits were reduced by NSC transplantation, including increase in NeuN-positive cells and decrease in apoptotic cells. Moreover, neurophysiological profiles indicated that the latent period was decreased and the peak-to-peak amplitude of spinal nerve fibers conduction was increased in transplanted rats, while morphological measures indicated that fractional anisotropy and the number of nerve fibers in the site of spinal cord injury were increased after NSC transplantation. In addition, mRNA and protein level of IGF-1 R were increased in the rostral segment in the NSC group, especially in neurons. Therefore, we concluded that NSC transplantation promotes motor function improvement of SCT, which might be associated with activated IGF-1 R, especially in the rostral site. All of the above suggests that this approach has potential for clinical treatment of spinal cord injury.

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“…Finally, the average data of the three trials was obtained. All animals were assessed 4 weeks after SCT 20,21 .…”

Section: Inclined Plane Testmentioning

confidence: 99%

Neural Stem Cell Transplantation Improves Locomotor Function in Spinal Cord Transection Rats Associated with Nerve Regeneration and IGF-1 R Expression

Zhao

Liu

et al. 2019

Cell Transplant

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“…In addition, NT3 further restored KCC2 expression by suppressing the hyper-excitatory state of the injured spinal cord [ 47 , 93 ] and induced an increased electrophysiological response and retrograde tracer transport [ 51 ]. When combined with rehabilitative training, GDNF and G-CSF induced neuroprotection [ 52 , 53 ], and a cocktail of neurotrophic factors induced neural regeneration when applied with cABC [ 54 ]. Because rehabilitative training, especially physical exercise, upregulates these neurotrophic factors regardless of chronicity [ 94 ], the treatment effect of trophic factor(s) will be enhanced when combined with training.…”

Section: Discussionmentioning

confidence: 99%

“…Many researchers reported negative results regarding gross tissue histology. A few studies reported tissue sparing, including suppression of cavity expansion or lesion extension, in combination with G-CSF and tamoxifen [ 52 , 83 ], and one study reported a positive trend with a growth factor cocktail [ 54 ], but studies on amphetamine, blood glucose scavenger, PKA inhibitor, and melatonin reported negative results [ 79 , 82 , 86 , 89 ]. Reporting bias might be involved because this assessment is fundamental.…”

Section: Discussionmentioning

confidence: 99%

Do Pharmacological Treatments Act in Collaboration with Rehabilitation in Spinal Cord Injury Treatment? A Review of Preclinical Studies

Tashiro,

Shibata,

Nagoshi

et al. 2024

Cells

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There is no choice other than rehabilitation as a practical medical treatment to restore impairments or improve activities after acute treatment in people with spinal cord injury (SCI); however, the effect is unremarkable. Therefore, researchers have been seeking effective pharmacological treatments. These will, hopefully, exert a greater effect when combined with rehabilitation. However, no review has specifically summarized the combinatorial effects of rehabilitation with various medical agents. In the current review, which included 43 articles, we summarized the combinatorial effects according to the properties of the medical agents, namely neuromodulation, neurotrophic factors, counteraction to inhibitory factors, and others. The recovery processes promoted by rehabilitation include the regeneration of tracts, neuroprotection, scar tissue reorganization, plasticity of spinal circuits, microenvironmental change in the spinal cord, and enforcement of the musculoskeletal system, which are additive, complementary, or even synergistic with medication in many cases. However, there are some cases that lack interaction or even demonstrate competition between medication and rehabilitation. A large fraction of the combinatorial mechanisms remains to be elucidated, and very few studies have investigated complex combinations of these agents or targeted chronically injured spinal cords.

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“…After a brain injury, astrogliosis (or reactive astrocytosis) is a critical process for healing the injured brain area. In a spinal cord injury model of rats, concomitant G-CSF treatment and exercise therapy are effective for motor function recovery [ 22 ]. In the current animal model, GFAP immunostaining indexes of CA1, CA3, and Purkinje neurons in the brain irradiation-G-CSF group were lower than in the brain irradiation-saline group.…”

Section: Discussionmentioning

confidence: 99%

Reparative, Neuroprotective and Anti-neurodegenerative Effects of Granulocyte Colony Stimulating Factor in Radiation-Induced Brain Injury Model

Gürkan¹,

Atasoy²,

Çini³

et al. 2023

J Korean Neurosurg Soc

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Objective : This animal model aimed to compare the rat group that received brain irradiation and did not receive additional treatment (only saline) and the rat group that underwent brain irradiation and received Granulocyte colony stimulating factor (G-CSF) treatment. In addition, the effects of G-CSF on brain functions were examined by magnetic resonance (MR) imaging and histopathologically.Methods : This study used 24 female Wistar albino rats. Drug administration (saline or G-CSF) was started at the beginning of the study and continued for 15 days after whole-brain radiotherapy (WBRT). WBRT was given on day 7 of the start of the study. At the end of 15 days, the behavioral tests, including the three-chamber sociability test, open field test, and passive avoidance learning test, were done. After the behavioral test, the animals performed the MR spectroscopy procedure. At the end of the study, cervical dislocation was applied to all animals.Results : G-CSF treatment positively affected the results of the three-chamber sociability test, open-space test and passive avoidance learning test, cornu Ammonis (CA) 1, CA3, and Purkinje neuron counts, and the brain levels of brain-derived neurotrophic factor and postsynaptic density protein-95. However, G-CSF treatment reduced the glial fibrillary acidic protein immunostaining index and brain levels of malondialdehyde, tumor necrosis factor-alpha, nuclear factor kappa-B, and lactate. In addition, on MR spectroscopy, G-CSF had a reversible effect on brain lactate levels.Conclusion : In this first designed brain irradiation animal model, which evaluated G-CSF effects, we observed that G-CSF had reparative, neuroprotective and anti-neurodegenerative effects and had increased neurotrophic factor expression, neuronal counts, and morphology changes. In addition, G-CSF had a proven lactate-lowering effect in MR spectroscopy and brain materials.

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The combined effect of granulocyte-colony stimulating factor (G-CSF) treatment and exercise in rats with spinal cord injury

Abstract: Combined treatment provided more effective neuroplasty and functional recovery than individual treatments.

Cited by 7 publications

References 29 publications

Neural Stem Cell Transplantation Improves Locomotor Function in Spinal Cord Transection Rats Associated with Nerve Regeneration and IGF-1 R Expression

Neural Stem Cell Transplantation Improves Locomotor Function in Spinal Cord Transection Rats Associated with Nerve Regeneration and IGF-1 R Expression

Do Pharmacological Treatments Act in Collaboration with Rehabilitation in Spinal Cord Injury Treatment? A Review of Preclinical Studies

Reparative, Neuroprotective and Anti-neurodegenerative Effects of Granulocyte Colony Stimulating Factor in Radiation-Induced Brain Injury Model

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