Immunization with a Neural-Derived Peptide Protects the Spinal Cord from Apoptosis after Traumatic Injury

Apoptosis is one of the most destructive mechanisms that develop after spinal cord (SC) injury. Immunization with neural-derived peptides (INDPs) such as A91 has shown to reduce the deleterious proinflammatory response and the amount of harmful compounds produced after SC injury. With the notion that the aforementioned elements are apoptotic inducers, we hypothesized that INDPs would reduce apoptosis after SC injury. In order to test this assumption, adult rats were subjected to SC contusion and immunized either with A91 or phosphate buffered saline (PBS; control group). Seven days after injury, animals were euthanized to evaluate the number of apoptotic cells at the injury site. Apoptosis was evaluated using DAPI and TUNEL techniques; caspase-3 activity was also evaluated. To further elucidate the mechanisms through which A91 exerts this antiapoptotic effects we quantified tumor necrosis factor-alpha (TNF-α). To also demonstrate that the decrease in apoptotic cells correlated with a functional improvement, locomotor recovery was evaluated. Immunization with A91 significantly reduced the number of apoptotic cells and decreased caspase-3 activity and TNF-αconcentration. Immunization with A91 also improved the functional recovery of injured rats. The present study shows the beneficial effect of INDPs on preventing apoptosis and provides more evidence on the neuroprotective mechanisms exerted by this strategy.

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Effects of Electroacupuncture and the Retinoid X Receptor (Rxr) Signalling Pathway on Oligodendrocyte Differentiation in the Demyelinated Spinal Cord of Rats

Acupuncture in Medicine ◽

10.1136/acupmed-2016-011134 ◽

2017 ◽

Vol 35 (2) ◽

pp. 122-132 ◽

Cited By ~ 3

Author(s):

Xiao-Hua Yang ◽

Ying Ding ◽

Wen Li ◽

Rong-Yi Zhang ◽

Jin-Lang Wu ◽

...

Keyword(s):

Spinal Cord ◽

Retinoid X Receptor ◽

Signalling Pathway ◽

Control Group ◽

Oligodendrocyte Differentiation ◽

Adult Rats ◽

Group Protein ◽

Embryonic Spinal Cord ◽

Oligodendrocyte Precursor

Objectives In spinal cord demyelination, some oligodendrocyte precursor cells (OPCs) remain in the demyelinated region but have a reduced capacity to differentiate into oligodendrocytes. This study investigated whether ‘Governor Vessel’ (GV) electroacupuncture (EA) would promote the differentiation of endogenous OPCs into oligodendrocytes by activating the retinoid X receptor γ (RXR-γ)-mediated signalling pathway. Methods Adult rats were microinjected with ethidium bromide (EB) into the T10 spinal cord to establish a model of spinal cord demyelination. EB-injected rats remained untreated (EB group, n=26) or received EA treatment (EB+EA group, n=26). A control group (n=26) was also included that underwent dural exposure without EB injection. After euthanasia at 7 days (n=5 per group), 15 days (n=8 per group) or 30 days (n=13 per group), protein expression of RXR-γ in the demyelinated spinal cord was evaluated by immunohistochemistry and Western blotting. In addition, OPCs derived from rat embryonic spinal cord were cultured in vitro, and exogenous 9-cis-RA (retinoic acid) and RXR-γ antagonist HX531 were administered to determine whether RA could activate RXR-γ and promote OPC differentiation. Results EA was found to increase the numbers of both OPCs and oligodendrocytes expressing RXR-γ and RALDH2, and promote remyelination in the remyelinated spinal cord. Exogenous 9-cis-RA enhanced the differentiation of OPCs into mature oligodendrocytes by activating RXR-γ. Conclusions The results suggest that EA may activate RXR signalling to promote the differentiation of OPCs into oligodendrocytes in spinal cord demyelination.

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Otoprotective Effects of Zingerone on Cisplatin-Induced Ototoxicity

International Journal of Molecular Sciences ◽

10.3390/ijms21103503 ◽

2020 ◽

Vol 21 (10) ◽

pp. 3503 ◽

Cited By ~ 2

Author(s):

Chang Ho Lee ◽

Da-hye Lee ◽

So Min Lee ◽

So Young Kim

Keyword(s):

Caspase 3 ◽

Auditory Brainstem ◽

Control Group ◽

Heme Oxygenase 1 ◽

Sprague Dawley ◽

Necrosis Factor Alpha ◽

Auditory Thresholds ◽

Expression Levels ◽

Brainstem Response ◽

Group A

Previous studies have described the effects of zingerone (ZO) on cisplatin (CXP)-induced injury to the kidneys, liver, and other organs but not to the cochlea. This study aimed to investigate the effects of ZO on CXP-induced ototoxicity. Eight-week-old Sprague–Dawley rats were used and divided into a control group, a CXP group, and a CXP + ZO group. Rats in the CXP group received 5 mg/kg/day CXP intraperitoneally for five days. Rats in the CXP + ZO group received 5 mg/kg/day CXP intraperitoneally for five days and 50 mg/kg/day ZO intraperitoneally for seven days. Auditory brainstem response thresholds (ABRTs) were measured before (day 0) and after (day 10) drug administration. Cochlear histology was examined using hematoxylin and eosin (H&E) staining and cochlear whole mounts. The expression levels of cytochrome P450 (CYP)1A1, CYP1B1, inducible nitric oxide synthase (iNOS), nuclear factor kappa B (NFκB), tumor necrosis factor alpha (TNFα), and interleukin 6 (IL6) were estimated using quantitative reverse transcription-polymerase chain reaction. The expression levels of heme oxygenase 1 (HO1) and caspase 3 were analyzed via Western blotting. The auditory thresholds at 4, 8, and 16 kHz were attenuated in the CXP + ZO group compared with the CXP group. The mRNA expression levels of CYP1A1, CYP1B1, iNOS, NFκB, TNFα, and IL6 were lower in the CXP + ZO group than in the CXP group. The protein expression levels of HO1 and caspase 3 were lower in the CXP + ZO group than in the CXP group. Cotreatment with ZO exerted otoprotective effects against CXP-induced cochlear injury via antioxidative and anti-inflammatory activities involving CYPs, iNOS, NFκB, and TNFα.

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Quantification of Locomotor Recovery following Spinal Cord Contusion in Adult Rats

Journal of Neurotrauma ◽

10.1089/neu.2006.23.1632 ◽

2006 ◽

Vol 23 (11) ◽

pp. 1632-1653 ◽

Cited By ~ 35

Author(s):

Melanie L. McEwen ◽

Joe E. Springer

Keyword(s):

Spinal Cord ◽

Adult Rats ◽

Locomotor Recovery ◽

Spinal Cord Contusion

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Adoptive transfer of M2 macrophages promotes locomotor recovery in adult rats after spinal cord injury

Brain Behavior and Immunity ◽

10.1016/j.bbi.2014.11.007 ◽

2015 ◽

Vol 45 ◽

pp. 157-170 ◽

Cited By ~ 79

Author(s):

Shan-Feng Ma ◽

Yue-Juan Chen ◽

Jing-Xing Zhang ◽

Lin Shen ◽

Rui Wang ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Adoptive Transfer ◽

M2 Macrophages ◽

Adult Rats ◽

Locomotor Recovery ◽

Cord Injury

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Metallothionein Induction Reduces Caspase-3 Activity and Tnfα Levels with Preservation of Cognitive Function and Intact Hippocampal Neurons in Carmustine-Treated Rats

Oxidative Medicine and Cellular Longevity ◽

10.4161/oxim.2.1.7901 ◽

2009 ◽

Vol 2 (1) ◽

pp. 26-35 ◽

Cited By ~ 22

Author(s):

Gouda K. Helal ◽

Abdulaziz M. Aleisa ◽

Omayma K. Helal ◽

Salim S. Al-Rejaie ◽

Abdulaziz A. Al-Yahya ◽

...

Keyword(s):

Normal Saline ◽

Hippocampal Neurons ◽

Caspase 3 ◽

Short Term Memory ◽

Control Group ◽

Albino Rats ◽

Necrosis Factor Alpha ◽

Factor Alpha ◽

Wistar Albino Rats ◽

Necrosis Factor

Hippocampal integrity is essential for cognitive functions. On the other hand, induction of metallothionein (MT) by ZnSO4and its role in neuroprotection has been documented. The present study aimed to explore the effect of MT induction on carmustine (BCNU)-induced hippocampal cognitive dysfunction in rats. A total of 60 male Wistar albino rats were randomly divided into four groups (15/group): The control group injected with single doses of normal saline (i.c.v) followed 24 h later by BCNU solvent (i.v). The second group administered ZnSO4(0.1 µmol/10 µl normal saline, i.c.v, once) then BCNU solvent (i.v) after 24 h. Third group received BCNU (20 mg/kg, i.v, once) 24 h after injection with normal saline (i.c.v). Fourth group received a single dose of ZnSO4(0.1 µmol/10 µl normal saline, i.c.v) then BCNU (20 mg/kg, i.v, once) after 24 h. The obtained data revealed that BCNU administration resulted in deterioration of learning and short-term memory (STM), as measured by using radial arm water maze, accompanied with decreased hippocampal glutathione reductase (GR) activity and reduced glutathione (GSH) content. Also, BCNU administration increased serum tumor necrosis factor-alpha (TNFα), hippocampal MT and malondialdehyde (MDA) contents as well as caspase-3 activity in addition to histological alterations. ZnSO4pretreatment counteracted BCNU-induced inhibition of GR and depletion of GSH and resulted in significant reduction in the levels of MDA and TNFα as well as the activity of caspase-3. The histological features were improved in hippocampus of rats treated with ZnSO4+ BCNU compared to only BCNU-treated animals. In conclusion, MT induction halts BCNU-induced hippocampal toxicity as it prevented GR inhibition and GSH depletion and counteracted the increased levels of TNFα, MDA and caspase-3 activity with subsequent preservation of cognition.

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Repetitive transcranial magnetic stimulation improves open field locomotor recovery after low but not high thoracic spinal cord compression-injury in adult rats

Journal of Neuroscience Research ◽

10.1002/jnr.10852 ◽

2004 ◽

Vol 75 (2) ◽

pp. 253-261 ◽

Cited By ~ 20

Author(s):

Anne-Lise Poirrier ◽

Yves Nyssen ◽

Felix Scholtes ◽

Sylvie Multon ◽

Charline Rinkin ◽

...

Keyword(s):

Spinal Cord ◽

Transcranial Magnetic Stimulation ◽

Magnetic Stimulation ◽

Repetitive Transcranial Magnetic Stimulation ◽

Cord Compression ◽

Compression Injury ◽

Adult Rats ◽

Thoracic Spinal Cord ◽

Locomotor Recovery ◽

Thoracic Spinal

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Neurotrophin Expressions in Neural Stem Cells Grafted Acutely to Transected Spinal Cord of Adult Rats Linked to Functional Improvement

Cellular and Molecular Neurobiology ◽

10.1007/s10571-012-9832-4 ◽

2012 ◽

Vol 32 (7) ◽

pp. 1089-1097 ◽

Cited By ~ 23

Author(s):

Ying-Li Gu ◽

Lu-Wei Yin ◽

Zhuo Zhang ◽

Jia Liu ◽

Su-Juan Liu ◽

...

Keyword(s):

Spinal Cord ◽

Stem Cells ◽

Neural Stem Cells ◽

Functional Improvement ◽

Adult Rats

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BDNF expression with functional improvement in transected spinal cord treated with neural stem cells in adult rats

Neuropeptides ◽

10.1016/j.npep.2012.06.001 ◽

2013 ◽

Vol 47 (1) ◽

pp. 1-7 ◽

Cited By ~ 23

Author(s):

Bao-Li He ◽

Ying-chun Ba ◽

Xu-yang Wang ◽

Su-juan Liu ◽

Guo-dong Liu ◽

...

Keyword(s):

Spinal Cord ◽

Stem Cells ◽

Neural Stem Cells ◽

Functional Improvement ◽

Bdnf Expression ◽

Adult Rats

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Apoptosis after traumatic human spinal cord injury

Neurosurgical FOCUS ◽

10.3171/foc.1999.6.1.10 ◽

1999 ◽

Vol 6 (1) ◽

pp. E9

Author(s):

Evelyne Emery ◽

Philipp Aldana ◽

Mary Bartlett Bunge ◽

William Puckett ◽

Anu Srinivasan ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Cell Death ◽

Programmed Cell Death ◽

Caspase 3 ◽

Positive Staining ◽

Apoptotic Cells ◽

Nuclear Staining ◽

Human Spinal Cord ◽

Cord Injury

Apoptosis is a form of programmed cell death seen in a variety of developmental and disease states, including traumatic injuries. The main objective of this study was to determine whether apoptosis is observed after human spinal cord injury (SCI). The spatial and temporal expression of apoptotic cells as well as the nature of the cells involved in programmed cell death were also investigated. The authors examined the spinal cords of 15 patients who died between 3 hours and 2 months after a traumatic SCI. Apoptotic cells were found at the edges of the lesion epicenter and in the adjacent white matter, particularly in the ascending tracts, by using histological (cresyl violet, hematoxylin and eosin) and nuclear staining (Hoechst 33342). The presence of apoptotic cells was supported by staining with the terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick-end labeling technique and confirmed by immunostaining for the processed form of caspase-3 (CPP-32), a member of the interleukin-1-beta-converting enzyme/Caenorhabditis elegans D 3 (ICE/CED-3) family of proteases that plays an essential role in programmed cell death. Apoptosis in this series of human SCIs was a prominent pathological finding in 14 of the 15 spinal cords examined when compared with five uninjured control spinal cords. To determine the type of cells undergoing apoptosis, the authors immunostained specimens with a variety of antibodies, including glial fibrillary acidic protein, 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase), and CD45/68. Oligodendrocytes stained with CNPase and a number of apoptotic nuclei colocalized with positive staining for this antibody. These results support the hypothesis that apoptosis occurs in human SCIs and is accompanied by the activation of caspase-3 of the cysteine protease family. This mechanism of cell death contributes to the secondary injury processes seen after human SCI and may have important clinical implications for the further development of protease inhibitors to prevent programmed cell death.

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