Treatment with Immunosuppressants FTY720 and Tacrolimus Promotes Functional Recovery after Spinal Cord Injury in Rats

Zhang, Jie; Zhang, Ailiang; Sun, Yu; Cao, Xiaojian; Zhang, Ning

doi:10.1620/tjem.219.295

Cited by 28 publications

(17 citation statements)

References 41 publications

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“…Therefore, it seems that EPO, and not tacrolimus, is the responsible for the higher BBB scores. The literature has shown similar 38 and different 39, 40 results, possibly due to different methodology in the investigations.…”

Section: Discussionmentioning

confidence: 94%

Effects of tacrolimus and erythropoietin in experimental spinal cord lesion in rats: functional and histological evaluation

Coutinho

Cristante²,

Filho³

et al. 2015

Spinal Cord

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Study design:Experimental study with rats.Objective:To evaluate functional and histological effects of tacrolimus (FK 506) and erythropoietin (EPO) after experimental spinal cord contusion injury (SCI).Setting:Brazil.Methods:Wistar rats (n=60) were submitted to SCI with the NYU Impactor system. The control group received saline; the EPO group received EPO; the group EPO+FK 506 received EPO associated with tacrolimus and the group FK 506 received tacrolimus only. The Sham group underwent SCI, but did not receive any drug. Locomotor function was evaluated after SCI by BBB (Basso, Beattie and Bresnahan) weekly and by the motor-evoked potential test in 42 days. The spinal cord was histologically evaluated.Results:There was a significant difference between treated and the control groups from the seventh day on for BBB scores, with no difference between the groups EPO and EPO+FK 506 by the end of the study. There were significant differences between groups for necrosis and bleeding, but not for hiperemia, degeneration and cellular infiltrate. Axon neuron count was different between all groups (P=0.001), between EPO+FK 506 and FK 506 (P=0.011) and between EPO+FK 506 and Sham (P=0.002). Amplitude was significantly different between all groups except between control and sham. For latency, there was no difference.Conclusions:This study did not reveal significant differences in the recovery of locomotor function, or in the histological and electrophysiological analysis in animals treated with EPO and tacrolimus after thoracic SCI.

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Section: Discussionmentioning

confidence: 94%

Effects of tacrolimus and erythropoietin in experimental spinal cord lesion in rats: functional and histological evaluation

Coutinho

Cristante²,

Filho³

et al. 2015

Spinal Cord

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“…Protective effects of fingolimod have now been observed in a large number of acute brain injury models, including cerebral ischemia (Liu et al, 2013), spinal cord injury (Lee et al, 2009a; Zhang et al, 2009), traumatic brain injury (Zhang et al, 2007), intracerebral hemorrhage (Rolland et al, 2013), and t-PA-induced hemorrhagic transformation (Campos et al, 2013) et al Some studies indicate that this protection is associated with decreased macrophage infiltration (Kaneider et al, 2004; Rausch et al, 2004; Wei et al, 2011; Zhang et al, 2007) and microglial activation (Gao et al, 2012; Jackson et al, 2011; Miron et al, 2010; Noda et al, 2013). After ICH, the number of cells positive for CD68 (a marker for macrophage and microglia) increased 7–8 fold in the cerebral parenchyma adjacent to the hematoma (Dahnovici et al, 2011), and numerous CD68-positive cells were also seen in infarcted tissue after brain ischemia (Krupinski et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

“…Although its mechanism of action in multiple sclerosis is thought to be peripheral and involve induction of lymphopenia, this agent does show protective effects in acute central nervous system injury models of cerebral ischemia (Hasegawa et al, 2010) and spinal cord injury (Lee et al, 2009a; Zhang et al, 2009). In a detailed study, we have found that fingolimod treatment decreases brain edema, apoptosis, and infarct volume and improves behavioral functions in rodents with ischemic stroke (Wei et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Fingolimod exerts neuroprotective effects in a mouse model of intracerebral hemorrhage

Barfejani

Qin

et al. 2014

Brain Research

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Recent studies have shown that fingolimod (FTY720) is neuroprotective in CNS injury models of cerebral ischemia and spinal cord injury. The purpose of the study was to examine the effect of fingolimod in a mouse model of intracerebral hemorrhage. ICH was produced in adult CD1 mice by injecting collagenase VII-S (0.5 μL, 0.06 U) into the basal ganglia. Fingolimod (or saline) was given 30 min after surgery and once daily for two days. Three days after intracerebral hemorrhage, brain edema, hematoma volume and the number of apoptotic cells were quantified. In another cohort of mice, brain atrophy was evaluated 2 weeks following intracerebral hemorrhage. Neurobehavioral tests were performed at 3, 7 and 14 days. Fingolimod significantly decreased edema, apoptosis and brain atrophy. More importantly, fingolimod enhanced neurobehavioral recovery. Preliminary experiments showed no difference in the number of inflammatory (CD68-positive) cells between the two groups. In conclusion, fingolimod exerts protective effects in a mouse model of intracerebral hemorrhage; the mechanisms underlying this neuroprotective effects deserves further study.

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“…However, some side effects from oral and intravenous administration of Tacrolimus in clinical case studies have been reported which include nephrotoxicity [7], lung damage [8], various neuropsychiatric problems, neurotoxic effects such as akinetic mutism and catatonic mutism [9,10]. On the contrary, in experimental studies, Tacrolimus improves the functional outcome of spinal cord injury [5,11,12] and has an in vivo neurotrophic action whereby it enhances the rate of axon regeneration leading to more rapid neurological recovery [13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Can Enforced Behavioral Activity in Spinal Cord Injured Rats be considered as Rehabilitation Process to Accentuate Tacrolimus Treated Recovery? A nursing Care Perspective

Ahmad¹,

Shaiqah²

2017

J Mult Scler

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Animal models for spinal cord injury (SCI) help in developing effective treatment modalities. The aim of the present study is to develop suitable rehabilitative intervention besides therapeutical agents for a better functional recovery. Furthermore, this research intends to bring awareness among the nurses for caring SCI patients and utilizing their passion of caring abilities in nursing research also. Young adult male rats were subjected to spinal trauma by compression method of the exposed spinal cord. Animals were allocated to five groups with eight animals in each, viz. Group 1 as normal uninjured control; group 2 as sham control with laminectomy but no spinal injury; group 3 as SCI group with laminectomy and spinal injury; group 4 as SCI treated group A that were same as group 3 but were treated with a daily injection of Tacrolimus (1 mg/kg) for 29 days and subjected to BBB behavioral test in which the hind limb function was scored from 0 (complete paralysis or paraplegia) to 21 (complete mobility), every alternate days in a "Gait Performance Tunnel" (GPT); group 5 as SCI treated group B that were same as group 4 except that the animals were also subjected to a daily enforced extra 5 walks as exercise in GPT. Although the drug had an attenuating effect on SCI in both treated groups A and B the recovery in Group-B was significantly (p<0.001) greater than Group-A. It is concluded that if the SCI animals are subjected to enforced daily behavioral exercises in addition to drug treatment, it can improve functional recovery at a faster rate and can be considered as a rehabilitative activity to accentuate therapeutic treatments. Furthermore, the present study can be a source of inspiration for the nurses to develop their nursing skills and research abilities.

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Treatment with Immunosuppressants FTY720 and Tacrolimus Promotes Functional Recovery after Spinal Cord Injury in Rats

Cited by 28 publications

References 41 publications

Effects of tacrolimus and erythropoietin in experimental spinal cord lesion in rats: functional and histological evaluation

Effects of tacrolimus and erythropoietin in experimental spinal cord lesion in rats: functional and histological evaluation

Fingolimod exerts neuroprotective effects in a mouse model of intracerebral hemorrhage

Can Enforced Behavioral Activity in Spinal Cord Injured Rats be considered as Rehabilitation Process to Accentuate Tacrolimus Treated Recovery? A nursing Care Perspective

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