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Melatonin alleviates acute spinal cord injury in rats through promoting on progenitor cells proliferation.

ABSTRACT: The previous studies have shown that melatonin is beneficial for nervous system after spinal cord injury (SCI). After SCI, the endogenous neural stem/progenitor cells (eNSPCs) proliferate and differentiate into neurons and glial cells. In the present study, we examined the effect of melatonin on eNSPCs proliferation and differentiation in SCI rat model. SCI rat model was established by dropping a 10 g rod from the height of 25 mm. Then, the rats were randomly divided into the control group, the melatonin treated group, and the G3335 treated group. The Basso-Beattie-Bresnahan locomotor rating scale (BBB scale) was used to evaluate the recovery of locomotor function after SCI. Flow cytometry was used to evaluate eNSPCs proliferation and differentiation. The rats in the melatonin treated group demonstrated significantly faster locomotor function recovery and more eNSPCs proliferation and differentiation. However, these effects were abolished in the G3335 treated group. Melatonin can effectively promote locomotor function recovery via improving eNSPCs proliferation and differentiation after SCI.

SUBMITTER: Zheng B

PROVIDER: S-EPMC5447434 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Melatonin alleviates acute spinal cord injury in rats through promoting on progenitor cells proliferation.

Zheng Bolong B Hao Dingjun D Guo Hua H He Baorong B

Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society 20170428 4

The previous studies have shown that melatonin is beneficial for nervous system after spinal cord injury (SCI). After SCI, the endogenous neural stem/progenitor cells (eNSPCs) proliferate and differentiate into neurons and glial cells. In the present study, we examined the effect of melatonin on eNSPCs proliferation and differentiation in SCI rat model. SCI rat model was established by dropping a 10 g rod from the height of 25 mm. Then, the rats were randomly divided into the control group, the ...[more]

PMID: 28579893

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Project description:BackgroundThere is emerging evidence that astaxanthin plays a significant role in protecting neuro-cells from apoptosis after central nervous system injury. Our study examined the effects of astaxanthin on neuro-cell apoptosis after spinal cord injury.MethodsOne hundred and forty-four healthy adult Sprague-Dawley rats were randomly divided into the experimental group, control group, and sham operation group (n=48). Spinal cord injury was induced using the modified Allen method in the control group and the experimental group; while in the sham operation group, the lamina was removed without spinal cord injury. The rats in the experimental group were given astaxanthin (75 mg/kg) by gavage immediately after the operation, and in the other groups were given the same amount of olive oil. Motor function was assessed by blood-brain barrier (BBB) scores. The malondialdehyde (MDA) content and the activity of superoxide dismutase (SOD) at 24 h was determined after the operation. The apoptosis index (AI) was determined at 6, 24, and 48 h after the operation. At 48 h after the operation, we calculated the water content of the spinal cord, the lesion ratio of the spinal cord, the ultrastructure of the spinal cord, and the ultrastructure score.ResultsThe BBB scores of the control and experimental groups were significantly lower than the sham operation group at each postoperative time (P<0.05), and the BBB score of the experimental group was significantly higher than the control group at 1-4 weeks postoperatively (P<0.05). At 24 hours postoperatively, MDA content was highest in the control group and lowest in the sham operation group, while SOD activity was highest in the sham operation group and lowest in the control group (P<0.05). At each time point postoperatively, the sham operation group had the lowest AI and the control group had the highest AI (P<0.05). At 48 h after the operation, the water content and the lesion ratio of the spinal cord, and the ultrastructure score were the lowest in the sham operation group and the highest in the control group (P<0.05).ConclusionsAstaxanthin significantly improved the motor function of rats with spinal cord injury.

Project description:BackgroundNafamostat mesylate (nafamostat, NM) is an FDA-approved serine protease inhibitor that exerts anti-neuroinflammation and neuroprotective effects following rat spinal cord injury (SCI). However, clinical translation of nafamostat has been limited by an unclear administration time window and mechanism of action.MethodsTime to first dose of nafamostat administration was tested on rats after contusive SCI. The optimal time window of nafamostat was screened by evaluating hindlimb locomotion and electrophysiology. As nafamostat is a serine protease inhibitor known to target thrombin, we used argatroban (Arg), a thrombin-specific inhibitor, as a positive control in the time window experiments. Western blot and immunofluorescence of thrombin expression level and its enzymatic activity were assayed at different time points, as well its receptor, the protease activated receptor 1 (PAR1) and downstream protein matrix metalloproteinase-9 (MMP9). Blood-spinal cord barrier (BSCB) permeability leakage indicator Evans Blue and fibrinogen were analyzed along these time points. The infiltration of peripheral inflammatory cell was observed by immunofluorescence.ResultsThe optimal administration time window of nafamostat was 2-12 h post-injury. Argatroban, the thrombin-specific inhibitor, had a similar pattern. Thrombin expression peaked at 12 h and returned to normal level at 7 days post-SCI. PAR1, the thrombin receptor, and MMP9 were significantly upregulated after SCI. The most significant increase of thrombin expression was detected in vascular endothelial cells (ECs). Nafamostat and argatroban significantly downregulated thrombin and MMP9 expression as well as thrombin activity in the spinal cord. Nafamostat inhibited thrombin enrichment in endothelial cells. Nafamostat administration at 2-12 h after SCI inhibited the leakage of Evans Blue in the epicenter and upregulated tight junction proteins (TJPs) expression. Nafamostat administration 8 h post-SCI effectively inhibited the infiltration of peripheral macrophages and neutrophils to the injury site.ConclusionsOur study provides preclinical information of nafamostat about the administration time window of 2-12 h post-injury in contusive SCI. We revealed that nafamostat functions through inhibiting the thrombin-mediated BSCB breakdown and subsequent peripheral immune cells infiltration.

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Melatonin alleviates acute spinal cord injury in rats through promoting on progenitor cells proliferation.

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Melatonin alleviates acute spinal cord injury in rats through promoting on progenitor cells proliferation.

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