Rabbit Spinal Cord Research Articles

Neuroprotective Effects of Chaperonin Containing TCP1 Subunit 2 (CCT2) on Motor Neurons Following Oxidative or Ischemic Stress.

Chaperonin containing TCP1 (CCT) is an essential protein that controls proteostasis following spinal cord damage. In particular, CCT2 plays an important role in neuronal death in various neurological disorders; however, few studies have investigated the effects of CCT2 on ischemic damage in the spinal cord. In the present study, we synthesized a cell-permeable Tat-CCT2 fusion protein and observed its effects on H2O2-induced oxidative damage in NSC34 motoneuron-like cells and in the spinal cord after ischemic injury. Tat-CCT2, but not its control protein CCTs, was delivered into NSC34 cells in a concentration- and incubation time-dependent manner, and a clear cytosolic location of the delivered protein was observed. In addition, the delivered protein gradually degraded, and nearly control levels were observed 24h after Tat-CCT2 treatment. Tat-CCT2 treatment significantly ameliorated 200 µM H2O2-induced neuronal damage in NSC34 cells at 8.0 µM protein treatment. Additionally, Tat-CCT2 significantly ameliorated H2O2-induced reactive oxygen species formation and DNA fragmentation. In the rabbit spinal cord, Tat-CCT2 was efficiently delivered into the spinal cord 4h after 0.125mg/kg protein treatment. In addition, treatment with Tat-CCT2 significantly improved the neurological scores based on the Tarlov criteria 24 and 72h after ischemia/reperfusion. Moreover, the number of surviving neurons in the ventral horn of the spinal cord was significantly increased in the Tat-CCT2-treated group 3 and 7 days after ischemia compared to vehicle-treated group. Treatment with Tat-CCT2 alleviated the ischemia-induced oxidative stress and ferroptosis-related factor (malondialdehyde, 8-iso-prostaglandin F2α, and high mobility group box 1) and pro-inflammatory cytokine (interleukin-1β, interleukin-6, and tumor necrosis factor-α) releases in the ventral horn of the spinal cord 8 and 24h after ischemia/reperfusion. In addition, Tat-CCT2 treatment significantly ameliorated ischemia-induced microglial activation in the ventral horn of spinal cord 24h after reperfusion. These results suggest that Tat-CCT2 mitigates ischemia-induced neuronal damage in the spinal cord.

Amantadine's Neuroprotective Effects in Rabbit Spinal Cord Ischemia/Reperfusion Model.

To examine the effects of amantadine, a drug with neuroprotective and anti-inflammatory activities on oxidative stress, tissue necrosis, apoptosis, and neurological recovery in an experimental rabbit spinal cord ischemia-reperfusion injury (SCIRI) model. A total of 32 rabbits were randomized into five groups: control, ischemia, vehicle, methylprednisolone (MP), and amantadine (AMT) (n=8/each). At 24th-hour neurological examination was performed, spinal cord tissues were collected, and biochemical and histopathological examinations were performed. When ischemia and vehicle groups were compared with control group, significant increase was seen in serum and tissue caspase-3, malondialdehyde (MDA), and myeloperoxidase (MPO) levels (p < 0.001); significant decrease was seen in serum and tissue catalase (CAT) levels (p < 0.001); and significant increase was seen in serum xanthine oxidase (XO) levels (p < 0.001). When the ischemia group and the MP and AMT groups were compared, low serum and tissue caspase-3 levels (p < 0.001), high serum and tissue CAT levels (p < 0.001), significantly low serum XO levels (p < 0.001), low serum and tissue MDA levels (p < 0.05) and tissue MPO levels (p < 0.001) were found. Both AMT and MP groups showed decreased histopathological score and higher number of normal neurons (p < 0.001) compared to ischemia group. Both AMT and MP showed better modified Tarlov scores compared to the ischemia group (p < 0.001). Our study found that AMT had antioxidant, anti-inflammatory, anti-apoptotic, and neuroprotective effects on SCIRI. We used biochemical, microscopic, and ultrastructural approaches to demonstrate these effects. AMT might be a candidate medication for SCIRI prophylaxis and treatment.

Cinnamaldehyde has ameliorative effects on rabbit spinal cord ischemia and reperfusion injury

Cinnamaldehyde has ameliorative effects on rabbit spinal cord ischemia and reperfusion injury

Spinal motoneurons respond aberrantly to serotonin in a rabbit model of cerebral palsy.

Cerebral palsy (CP) is caused by a variety of factors that damage the developing central nervous system. Impaired motor control, including muscle stiffness and spasticity, is the hallmark of spastic CP. Rabbits that experience hypoxic-ischaemic (HI) injury in utero (at 70%-83% gestation) are born with muscle stiffness, hyperreflexia and, as recently discovered, increased 5-HT in the spinal cord. To determine whether serotonergic modulation of spinal motoneurons (MNs) contributes to motor deficits, we performed ex vivo whole cell patch clamp in neonatal rabbit spinal cord slices at postnatal day (P) 0-5. HI MNs responded to the application of α-methyl 5-HT (a 5-HT1 /5-HT2 receptor agonist) and citalopram (a selective 5-HT reuptake inhibitor) with increased amplitude and hyperpolarization of persistent inward currents and hyperpolarized threshold voltage for action potentials, whereas control MNs did not exhibit any of these responses. Although 5-HT similarly modulated MN properties of HI motor-unaffected and motor-affected kits, it affected sag/hyperpolarization-activated cation current (Ih ) and spike frequency adaptation only in HI motor-affected MNs. To further explore the differential sensitivity of MNs to 5-HT, we performed immunostaining for inhibitory 5-HT1A receptors in lumbar spinal MNs at P5. Fewer HI MNs expressed the 5-HT1A receptor compared to age-matched control MNs. This suggests that HI MNs may lack a normal mechanism of central fatigue, mediated by 5-HT1A receptors. Altered expression of other 5-HT receptors (including 5-HT2 ) likely also contributes to the robust increase in HI MN excitability. In summary, by directly exciting MNs, the increased concentration of spinal 5-HT in HI-affected rabbits can cause MN hyperexcitability, muscle stiffness and spasticity characteristic of CP. Therapeutic strategies that target serotonergic neuromodulation may be beneficial to individuals with CP. KEY POINTS: We used whole cell patch clamp electrophysiology to test the responsivity of spinal motoneurons (MNs) from neonatal control and hypoxia-ischaemia (HI) rabbits to 5-HT, which is elevated in the spinal cord after prenatal HI injury. HI rabbit MNs showed a more robust excitatory response to 5-HT than control rabbit MNs, including hyperpolarization of the persistent inward current and threshold voltage for action potentials. Although most MN properties of HI motor-unaffected and motor-affected kits responded similarly to 5-HT, 5-HT caused larger sag/hyperpolarization-activated cation current (Ih ) and altered repetitive firing patterns only in HI motor-affected MNs. Immunostaining revealed that fewer lumbar MNs expressed inhibitory 5-HT1A receptors in HI rabbits compared to controls, which could account for the more robust excitatory response of HI MNs to 5-HT. These results suggest that elevated 5-HT after prenatal HI injury could trigger a cascade of events that lead to muscle stiffness and altered motor unit development.

Neuroprotective Effects of Niacin on Ischemia/Reperfusion Injury of the Rabbit Spinal Cord

Previous studies have shown niacin has neuroprotective effects on the central nervous system. However, its specific effect on spinal cord ischemia/reperfusion injury has not yet been explored. This study aims to evaluate whether niacin can contribute neuroprotective effects on spinal cord ischemia/reperfusion injury. Rabbits were randomized into 4 groups of 8 animals: group I (control), group II (ischemia), group III (30mg/kg methylprednisolone, intraperitoneal), and group IV (500mg/kg niacin, intraperitoneal). The rabbits in group IV were premedicated with niacin for 7days prior to inducing ischemia/reperfusion injury. The control group was subjected only to a laparotomy, while the remaining groups underwent spinal cord ischemia through a 20-minute occlusion of the aorta caudal to the left renal artery. Following the procedure, levels of catalase, malondialdehyde, xanthine oxidase, myeloperoxidase, and caspase-3 were analyzed. Ultrastructural, histopathological, and neurological evaluations were also performed. Spinal cord ischemia/reperfusion injury resulted in increased levels of xanthine oxidase, malondialdehyde, myeloperoxidase, and caspase-3, with a concomitant decrease in catalase levels. Treatment with methylprednisolone and niacin led to decreased levels of xanthine oxidase, malondialdehyde, myeloperoxidase, and caspase-3 and an increase in catalase. Both methylprednisolone and niacin treatments demonstrated improvements in histopathological, ultrastructural, and neurological assessments. Our findings suggest that niacin has antiapoptotic, anti-inflammatory, antioxidant, and neuroprotective effects at least equal to methylprednisolone in ischemia/reperfusion injury of the spinal cord. This study is the first to report the neuroprotective impact of niacin on spinal cord ischemia/reperfusion injury. Further research is warranted to elucidate the role of niacin in this context.

Mildronate Has Ameliorative Effects on the Experimental Ischemia/Reperfusion Injury Model in the Rabbit Spinal Cord

Mildronate is a useful anti-ischemic agent and has antiinflammatory, antioxidant, and neuroprotective activities. The aim of this study is to investigate the potential neuroprotective effects of mildronate in the experimental rabbit spinal cord ischemia/reperfusion injury (SCIRI) model. Rabbits were randomized into 5 groups of 8 animals as groups 1 (control), 2 (ischemia), 3 (vehicle), 4 (30 mg/kg methylprednisolone [MP]), and 5 (100 mg/kg mildronate). The control group underwent only laparotomy. The other groups have the spinal cord ischemia model by a 20-minute aortic occlusion just caudal to the renal artery. The malondialdehyde and catalase levels and caspase-3, myeloperoxidase, and xanthine oxidase activities were investigated. Neurologic, histopathologic, and ultrastructural evaluations were also performed. The serum and tissue myeloperoxidase, malondialdehyde, and caspase-3 values of the ischemia and vehicle groups were statistically significantly higher than those of the MP and mildronate groups (P < 0.001). Serum and tissue catalase values of the ischemia and vehicle groups were statistically significantly lower than those of the control, MP, and mildronate groups (P < 0.001). The histopathologic evaluation showed a statistically significantly lower score in the mildronate and MP groups than in the ischemia and vehicle groups (P < 0.001). The modified Tarlov scores of the ischemia and vehicle groups were statistically significantly lower than those of the control, MP, and mildronate groups (P < 0.001). This study presented the antiinflammatory, antioxidant, antiapoptotic, and neuroprotective effects of mildronate on SCIRI. Future studies will elucidate its possible use in clinical settings in SCIRI.

Local host response of commercially available dural patches for fetal repair of spina bifida aperta in rabbit model.

Fetal surgery for spina bifida aperta (SBA) by open hysterotomy typically repairs anatomical native tissue in layers. Increasingly, fetoscopic repair is performed using a dural patch followed by skin closure. We studied the host response to selected commercially available patches currently being used in a fetal rabbit model for spina bifida repair. SBA was surgically induced at 23-24days of gestation (term=31days). Fetal rabbits were assigned to unrepaired (SBA group), or immediate repair with Duragen™ or Durepair™. Non-operated littermates served as normal controls. At term, spinal cords underwent immunohistochemical staining including Nissl and glial fibrillary acidic protein. We hypothesized that spinal cord coverage with a dural patch and skin closure would preserve motor neuron density within the non-inferiority limit of 201.65cells/mm2 and reduce inflammation compared to unrepaired SBA fetuses. Motor neuron density assessed by Nissl staining was conserved both by Duragen (n=6, 89.5; 95% CI -158.3 to -20.6) and Durepair (n=6, 37.0; 95% CI -132.6 to -58.5), whereas density of GFAP-positive cells to quantify inflammation was lower than in unrepaired SBA-fetuses (SBA 2366.0±669.7cells/mm2 vs. Duragen 1274.0±157.2cells/mm2 ; p=0.0002, Durepair 1069.0±270.7cells/mm2 ; p<0.0001). Covering the rabbit spinal cord with either Duragen or Durepair followed by skin closure preserves motor neuron density and reduces the inflammatory response.

Neuroprotective Effects of Dexpanthenol on Rabbit Spinal Cord Ischemia/Reperfusion Injury Model

Dexpanthenol (DXP) reportedly protects tissues against oxidative damage in various inflammation models. This study aimed to evaluate its effects on oxidative stress, inflammation, apoptosis, and neurological recovery in an experimental rabbit spinal cord ischemia/reperfusion injury (SCIRI) model. Rabbits were randomized into 5 groups of 8 animals each: group 1 (control), group 2 (ischemia), group 3 (vehicle), group 4 (methylprednisolone, 30mg/kg), and group 5 (DXP, 500mg/kg). The control group underwent laparotomy only, whereas other groups were subjected to spinal cord ischemia by aortic occlusion (just caudal to the 2 renal arteries) for 20min. After 24h, a modified Tarlov scale was employed to record neurological examination results. Malondialdehyde and caspase-3 levels and catalase and myeloperoxidase activities were analyzed in tissue and serum samples. Xanthine oxidase activity was measured in the serum. Histopathological and ultrastructural evaluations were also performed in the spinal cord. After SCIRI, serum and tissue malondialdehyde and caspase-3 levels and myeloperoxidase and serum xanthine oxidase activities were increased (P<0.05-0.001). However, serum and tissue catalase activity decreased significantly (P<0.001). DXP treatment was associated with lower malondialdehyde and caspase-3 levels and reduced myeloperoxidase and xanthine oxidase activities but increased catalase activity (P<0.05-0.001). Furthermore, DXP was associated with better histopathological, ultrastructural, and neurological outcome scores. This study was the first to evaluate antioxidant, anti-inflammatory, antiapoptotic, and neuroprotective effects of DXP on SCIRI. Further experimental and clinical investigations are warranted to confirm that DXP can be administered to treat SCIRI.

Blocking SP/NK1R signaling improves spinal cord hemisection by inhibiting the release of pro-inflammatory cytokines in rabbits

Objective Incomplete spinal cord injury (SCI) is the most common spinal cord injury in clinic, however its mechanism is still not fully understood. Design We constructed the rabbit spinal cord hemisection (SCH) model and used RT–PCR, western blotting, immunohistochemistry, and immunofluorescence experiments to explore the potential mechanism of SCI. Setting The sham operation (SH) group, the observation (OB, which is the SCH) group, the OB+ substance p (SP) inhibitor group, the OB + NK1R inhibitor group, the OB + NK1R agonist group and the OB + SP inhibitor + NK1R agonist group. Participants New Zealand white rabbits. Interventions Use NK1R inhibitors, NK1R agonists, SP inhibitors to treat the SCH model. Outcome Measures IL-1β, IKKγ, IL-6 and NF-κB. Results The results showed that nissl bodies, inflammatory cells and SP increased notably in the spinal cord cells of the rabbit SCH model. Through in vivo experiments with SP or NK1R inhibitors or NK1R agonists, we found that inhibiting SP/NK1R signaling can help improve SCH by inhibiting the release of pro-inflammatory cytokines IL-1β, IKKγ, IL-6 and NF-κB. Registered trials Animal experiments were approved by Ruijin Hospital, Shanghai Jiaotong University School of Medicine.

Tanshinone Protects against Spinal Cord Ischemia-Reperfusion Injury by Inhibiting JNK Activity.

Spinal cord reperfusion injury as a secondary damage after primary spinal cord injury is an important factor causing nerve cell damage. In this study, we aim to investigate the effects and mechanisms of tanshinone (TAE) in the rabbit spinal cord during ischemia-reperfusion. New Zealand white rabbits were randomly divided into 3 groups: sham-operated group (5 rabbits), ischemia-reperfusion group (0.9% TAE was administered intraperitoneally 30 min before ischemia, and 4 groups of 5 rabbits each according to different time periods of reperfusion: group A reperfused for 0.5 h, group B reperfused for 2 h, group C reperfused for 8 h, and group D reperfused for 24 h), and TAE group (an ischemia-reperfused for 24 h). Group A was reperfused for 0.5 h, group B for 2 h, group C for 8 h, group D for 24 h, and group TAE (TAE was applied 30 min before ischemia reperfusion, grouped as ischemia-reperfusion group). The expression of JNK (c-Jun NH2-terminal Kinase) and phosphorylation-JNK (p-JNK) in spinal cord tissues of each group were detected by Western blot. Light and electron microscopy showed that early apoptosis started in group B in the ischemia-reperfusion group, while early apoptosis appeared only in group D in the tanshinone intervention group. Western blot showed that p-JNK expression started in group B in the ischemia-reperfusion group and gradually increased with the prolongation of ischemia time, while p-JNK expression only increased in group D in the tanshinone intervention group. In the tanshinone intervention group, p-JNK was activated only in group D and its activity was less than that in the ischemia-reperfusion group; the protein expression of JNK did not change significantly in both groups. Spinal cord ischemia-reperfusion can cause spinal cord injury by activating the signaling molecule JNK (MRPKs family), and early tanshinone intervention can partially inhibit this injury. Our finding provides a new idea and theoretical basis for clinical treatment of spinal cord ischemia-reperfusion injury.

Remote conditioning as protective strategy influencing ubiquitin-mediated stress response in the rabbit spinal cord after ischemia/reperfusion.

The aim of presented study was to investigate the model of non-invasive method of remote conditioning induced by compression of left forelimb with a tourniquet in three cycles of 2 min of ischemia each followed by 2 min of reperfusion and its influence on the rabbit spinal cord ischemia/reperfusion injury via ubiquitin-mediated stress response. Ubiquitin immunoreaction in spinal cord motor neurons as well as detection of neuronal survival in ventral horns of spinal cord were evaluated. Significantly increased (p < 0.001) number of ubiquitin positive neurons was registered in all remote conditioned groups versus both spinal cord ischemia (SC-ischemia) groups. Our results indicate that remote conditioning significantly attenuated degeneration of motor neurons in all conditioned groups versus SC-ischemia groups in each time point. According to our results, we concluded that the remote conditioning induced by transient limb ischemia is relevant stimulus that provides potent neuroprotection in a model of spinal cord ischemia/ reperfusion injury.

The ameliorative effects of dexpanthenol on oxidative stress, inflammation, apoptosis and neurological functions of the experimental ischemia/reperfusion injury model in the rabbit spinal cord

The ameliorative effects of dexpanthenol on oxidative stress, inflammation, apoptosis and neurological functions of the experimental ischemia/reperfusion injury model in the rabbit spinal cord

Does Anzer Propolis Have a Protective Effect on Rabbit Spinal Cord Ischemia/Reperfusion Injury?

IntroductionIn this study, Anzer propolis, which can only be obtained from the Eastern Black Sea region in Turkey, is studied for its effect on spinal cord ischemia/reperfusion injury.MethodsA total of 12 healthy male New Zealand White rabbits with an average weight of 3.0 to 3.5 kg were separated into two blind and randomized groups: the ischemia/reperfusion group (n=6) and the treatment group (n=6). Each rabbit in the treatment group was given a dose of 100 mg/kg of ethanol-dissolved Anzer propolis orally 1 hour before surgery. Blood samples were examined at the 0th hour and postoperatively at the 24th and 48th hours. Tissue samples were taken at the 48th hour during the sacrification.ResultsThere was a statistically significant difference between the two groups in terms of postoperative Tarlov scoring (P=0.012). There was a difference between the two groups in terms of the blood levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) at the 48th hour, myeloperoxidase (MPO) at the 24th and 48th hours, ischemia-modified albumin (IMA) at the 24th hour, and intercellular adhesion molecule-1 (ICAM-1) and total oxidant status (TOS) at the 48th hour (P<0.005). There was also a difference between the two groups in terms of apoptotic index data obtained with the terminal deoxynucleotidyl transferase (TdT)‐mediated dUTP nick‐end labelling (TUNEL) method in the histopathological examination (P=0.001). In the transmission electron microscopic (TEM) analysis, while ischemia/reperfusion group generally had axon-myelin separation, axoplasmic dissolution and myelin separation, the propolis treatment group had normal myelin sequencing.DiscussionIn our study, after biochemical, histopathological, ultrastructural and neurological functional examination, it was demonstrated that Anzer propolis has sufficient neuroprotective effect on spinal cord ischemia/reperfusion injury in rabbits.

The effects of cerebrolysin on oxidative stress, inflammation, apoptosis and neurological recovery in experimental rabbit Spinal Cord Ischemia/Reperfursion injury model

The effects of cerebrolysin on oxidative stress, inflammation, apoptosis and neurological recovery in experimental rabbit Spinal Cord Ischemia/Reperfursion injury model

Tat-p27 Ameliorates Neuronal Damage Reducing α-Synuclein and Inflammatory Responses in Motor Neurons After Spinal Cord Ischemia.

p27Kip1(p27) regulates the cell cycle by inhibiting G1 progression in cells. Several studies have shown conflicting results on the effects of p27 against cell death in various insults. In the present study, we examined the neuroprotective effects of p27 against H2O2-induced oxidative stress in NSC34 cells and against spinal cord ischemia-induced neuronal damage in rabbits. To promote delivery into NSC34 cells and motor neurons in the spinal cord, Tat-p27 fusion protein and its control protein (Control-p27) were synthesized with or without Tat peptide, respectively. Tat-p27, but not Control-27, was efficiently introduced into NSC34 cells in a concentration- and time-dependent manner, and the protein was detected in the cytoplasm. Tat-p27 showed neuroprotective effects against oxidative stress induced by H2O2 treatment and reduced the formation of reactive oxygen species, DNA fragmentation, and lipid peroxidation in NSC34 cells. Tat-p27, but not Control-p27, ameliorated ischemia-induced neurological deficits and cell damage in the rabbit spinal cord. In addition, Tat-p27 treatment reduced the expression of α-synuclein, activation of microglia, and release of pro-inflammatory cytokines such as interleukin-1β and tumor necrosis factor-α in the spinal cord. Taken together, these results suggest that Tat-p27 inhibits neuronal damage by decreasing oxidative stress, α-synuclein expression, and inflammatory responses after ischemia.

Induction of ischemic tolerance by remote perconditioning or postconditioning as neuroprotective strategy for spinal cord motor neurons

AimsThe study is focused on the investigation of the mechanisms leading to ischemic tolerance acquisition in the spinal cord neurons via application of non-invasive method of remote conditioning. Material and methodsWe have verified the possibility of neuroprotection of spinal cord in rabbit by using remote perconditioning (PerC) applied during last 12 min of spinal cord ischemia (SC-ischemia) or postconditioning (PostC) applied after 1st (early) or 3rd (late) h of reperfusion. Spinal cord ischemia was induced by occlusion of the aorta below the left renal artery for 20 min. Reperfusion period was 24 or 72 h. Remote conditioning was induced by compression of left forelimb with a tourniquet in 3 cycles of 2 min of ischemia, each followed by 2 min of reperfusion. Damaged neurons were detected by Fluoro Jade B method and the modified Tarlov score was used for functional assessment. Key findingsThe remote conditioning significantly attenuated degeneration of motor neurons in all remote conditioned groups versus both SC-ischemia groups. We detected significant changes in number of Hsp70 positive motor neurons. At 72time point, in the group with remote late PostC we observed significant increase (p < 0.001) of Hsp70 positive motor neurons versus SC- ischemia group and sham control. There was a trend towards improvement of hindlimbs movement. SignificanceThis study showed the effectiveness of remote conditioning as a neuroprotective strategy, evidenced by induction of ischemic tolerance leading to decrease of motor neuron degeneration.

Cinnamaldehyde has ameliorative effects on rabbit spinal cord ischemia and reperfusion injury

Cinnamaldehyde has ameliorative effects on rabbit spinal cord ischemia and reperfusion injury

Phosphoglycerate Mutase 1 Prevents Neuronal Death from Ischemic Damage by Reducing Neuroinflammation in the Rabbit Spinal Cord.

Phosphoglycerate mutase 1 (PGAM1) is a glycolytic enzyme that increases glycolytic flux in the brain. In the present study, we examined the effects of PGAM1 in conditions of oxidative stress and ischemic damage in motor neuron-like (NSC34) cells and the rabbit spinal cord. A Tat-PGAM1 fusion protein was prepared to allow easy crossing of the blood-brain barrier, and Control-PGAM1 was synthesized without the Tat peptide protein transduction domain. Intracellular delivery of Tat-PGAM1, not Control-PGAM1, was achieved in a time- and concentration-dependent manner. Immunofluorescent staining confirmed the intracellular expression of Tat-PGAM1 in NSC34 cells. Tat-PGAM1, but not Control-PGAM1, significantly alleviated H2O2-induced oxidative stress, neuronal death, mitogen-activated protein kinase, and apoptosis-inducing factor expression in NSC34 cells. After ischemia induction in the spinal cord, Tat-PGAM1 treatment significantly improved ischemia-induced neurological impairments and ameliorated neuronal cell death in the ventral horn of the spinal cord 72 h after ischemia. Tat-PGAM1 treatment significantly mitigated the ischemia-induced increase in malondialdehyde and 8-iso-prostaglandin F2α production in the spinal cord. In addition, Tat-PGAM1, but not Control-PGAM1, significantly decreased microglial activation and secretion of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α induced by ischemia in the ventral horn of the spinal cord. These results suggest that Tat-PGAM1 can be used as a therapeutic agent to reduce spinal cord ischemia-induced neuronal damage by lowering the oxidative stress, microglial activation, and secretion of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α.

Therapeutic effects of rapamycin and surgical decompression in a rabbit spinal cord injury model

Surgical decompression after spinal cord injury (SCI) is a conventional treatment. Although it has been proven to have clinical effects, there are certain limitations, such as the surgical conditions that must be met and the invasive nature of the treatment. Therefore, there is an urgent need to develop a simple and maneuverable therapy for the emergency treatment of patients with SCI before surgery. Rapamycin (RAPA) has been reported to have potential as a therapeutic agent for SCI. In this study, we observed the therapeutic effects of rapamycin and surgical decompression, in combination or separately, on the histopathology in rabbits with SCI. After combination therapy, intramedullary pressure (IMP) decreased significantly, autophagic flux increased, and apoptosis and demyelination were significantly reduced. Compared with RAPA/surgical decompression alone, the combination therapy had a significantly better effect. In addition, we evaluated the effects of mechanical pressure on autophagy after SCI by assessing changes in autophagic initiation, degradation, and flux. Increased IMP after SCI inhibited autophagic degradation and impaired autophagic flux. Decompression improved autophagic flux after SCI. Our findings provide novel evidence of a promising strategy for the treatment of SCI in the future. The combination therapy may effectively improve emergency treatment after SCI and promote the therapeutic effect of decompression. This study also contributes to a better understanding of the effects of mechanical pressure on autophagy after neurotrauma.

The efficacy of adalimumab on experimentally induced spinal cord ischemia-reperfusion injury

Objective: Paraplegia is a dangerous complication of thoracoabdominal aortic surgery. Various studies have been conducted on the prevention of this complication and some spinal cord protection methods have been proposed. However, there is not any modality that prevent the development of paraplegia certainly. In the I / R period, primary injury triggers secondary injury due to increased inflammation, apoptosis and free radical formation. In this study, we evaluated that the neuroprotective effect of adalimumab in spinal cord ischemia-reperfusion injury. &#x0D; Materials and Methods: In total, 24 adult New Zealand rabbits were divided into three groups: Group 1, control; Group 2, ischemia-reperfusion by infrarenal aortic clamping; Group 3, adalimumab treated followed by ischemia. Tissue and plasma tumor necrosis factor alpha, interleukin 6, interleukin 10, thiobarbituric acid reactive substance, total oxidant status and total antioxidant status levels were analyzed as a marker of inflammation and oxidation. Histopathological evaluation of the tissues was performed, and apoptosis was evaluated by TUNNEL method.&#x0D; Results: I/R injury significantly increases plasma and spinal cord tissue at TNF alpha, TOS, TBARS, IL6 levels and reduces plasma and spinal cord tissue to TAS and IL10 levels. Adalimumab treatment significantly reduces plasma and spinal cord tissue to TNF alpha, TOS, TBARS, IL6 and increases plasma and tissue to TAS and IL10 levels.&#x0D; Conclusion: Adalimumab treatment significantly reduces the spinal cord neuronal damage score and the number of apoptotic cells. This paper aims to demonstrate the important neuroprotective effects of adalimumab on rabbit spinal cord I/R injury.