Acute Spinal Cord Contusion Injury Research Articles

The method of quantitative assessment of posttraumatic spinal cord injury volume and structure in animal models using magnetic resonance tomography

Introduction. Spinal cord injury is a debilitating traumatic event in central nervous system resulting in tissue destruction and severe neurological deficit development. Preclinical assessment of quantitative lesion area parameters (e. g. structure and volume) is critical for subsequent evaluation of neuroprotective and / or neuroregenerative therapy efficiency. Current methods for parameter calculation require manual limitation of the interested area (region of interest, RoI). This process is tedious and often not precise enough.Study objective is to develop and implement software for automated assessment of volume and structure of posttraumatic spinal cord lesion using extra-high-field MRI 7.0 Tesla and to compare methods preciseness with the current manual techniques.Study design. Ten rat models of acute severe spinal cord contusion injury were used including female Sprague–Dawley animals weighting 250–350 gr. MRI imaging was performed in 1 day postoperative and then 4 times with interval (1 week). Study was prospective open-label uncontrolled comparative.Materials and methods. Standard spinal cord contusion injury model was used. Anesthetized animals underwent laminectomy at level Th9–Th10 vertebrae followed by “weight drop” injury technique application: 10 g weight with 2 mm pin diameter dropped from 25 mm height. Software was developed using Microsoft Visual Studio 2017 environment and programming language C#. Statistical analysis was performed using IBM SPSS Statistics 21.0 software.Results. We developed and patented specialized software Spinal cavity Searcher realizing the algorithm of T2‑weighted images (T2‑WI) analysis based on image bynarization and Freeman chain code. This algorithm supports calculation of spinal cord posttraumatic lesion parameters in a half-automatic manner. Results of this algorithm application were comparable to results of manual calculation: no statistical difference were observed between two values.Conclusion. Current method of spinal cord injury volume and structure quantitative assessment simplifies the calculation procedure due to automatization of RoI limitation comparing to manual technique. The level of preciseness is comparable in both methods.Clinical relevance. The developed algorithm optimizes the process of non-invasive control of the performed treatment efficiency according to 7.0 Tesla MRI data.

Multicenter, randomized, double-blind placebo-control intramedullary decompression for acute complete spinal cord contusion injury

Introduction:Spinal cord injury is one of the main causes of severe neurological trauma and disability. Intramedullary decompression of acute spinal cord contusion in acute phase is one of the important therapeutic exploration methods. Due to the lack of multicenter, randomized, double-blind, placebo-controlled clinical studies, true effect of this treatment remains controversial.Objective of the study:This design of the study is to explore the safety and neurorestorative effects of intramedullary decompression for acute complete spinal cord contusion injury.Design of the study:We design the prospective, multicenter, randomized, double- blind placebo-controlled trial (MRDPT) for acute (less than 24 hours after injury) spinal cord contusion injury. Sixty patients with acute complete spinal cord contusion injury (20 in cervical 4 to thoracic 1, 20 in thoracic 2 to thoracic 9, and 20 in thoracic 10 to lumbar vertebra 1) are selected according to the selected conditions. All patients receive conventional treatments such as reduction and fixation of spinal fractures and/or spinal spondylolisthesis, bone external decompression relieves spinal cord compression. At the same time, group A (n = 30, 10 of each segment group) undergoes intramedullary decompression surgery and group B (n = 30) does not undergo intramedullary decompression. All relevant functional changes before, after, and during the follow-up period are recorded to ensure objective evaluation of the results of the treatment.Ethics and dissemination:The clinical study protocol and consent form were approved by China Branch of International Association of Neurorestoratology and the ethics committees of the hospitals which join this trial. Registration No. of this study is ChiCTR1800020458. Findings will be published in peer-reviewed journals.

PPP1CC is associated with astrocyte and microglia proliferation after traumatic spinal cord injury in rats

Reactive astrogliosis and microgliosis after spinal cord injury (SCI) contribute to glial scar formation that impedes axonal regeneration. The mechanisms underlying reactive astrocyte and microglia proliferation upon injury remain partially understood. Protein phosphatase 1, catalytic subunit, gamma isozyme (PPP1CC) participates in cell proliferation, differentiation and apoptosis. However, the expression and functions of PPP1CC following SCI are still unknown. In this study, an acute spinal cord contusion injury model in adult rats was established to investigate the potential role of PPP1CC during the pathological process of SCI. The palpable expression increase of PPP1CC after SCI was found by western blot and immunohistochemistry staining. Double immunofluorescence staining showed that PPP1CC expression mainly increased in astrocytes and microglia, as well as PPP1CC and proliferating cell nuclear antigen (PCNA) co-localized in astrocytes and microglia. Furthermore, PCNA expression also elevated after SCI in a similar manner as PPP1CC. In vitro, PPP1CC and PCNA expression in primary rat spinal cord astrocytes and microglia changed in a similar concentration- and time-dependent manner according to LPS treatment. In addition, PPP1CC knockdown in astrocytes and microglia resulted in the decrease of PCNA expression and the number of Brdu positive cells after LPS stimulation, showing that PPP1CC promoted astrocyte and microglia proliferation after inflammation. In a word, PPP1CC might be associated with astrocyte and microglia proliferation after SCI, implying that PPP1CC is a potential molecular target for the therapy of SCI.

FK506 Attenuates the Inflammation in Rat Spinal Cord Injury by Inhibiting the Activation of NF-κB in Microglia Cells.

FK-506 (Tacrolimus) is a very commonly used immunomodulatory agent that plays important roles in modulating the calcium-dependent phosphoserine-phosphothreonine protein phosphatase calcineurin and thus inhibits calcineurin-mediated secondary neuronal damage. The biological function of FK-506 in the spinal cord has not been fully elucidated. To clarify the anti-inflammatory action of FK-506 in spinal cord injury (SCI), we performed an acute spinal cord contusion injury model in adult rats and hypoxia-treated primary spinal cord microglia cultures. This work studied the activation of NF-κB and proinflammatory cytokine (TNF-a, IL-1b, and IL-6) expression. ELISA and q-PCR analysis revealed that TNF-a, IL-1b, and IL-6 levels significantly increased 3days after spinal cord contusion and decreased after 14days, accompanied by the increased activation of NF-κB. This increase was reversed by an FK-506 treatment. Double immunofluorescence labeling suggested that NF-κB activation was especially prominent in microglia. Immunohistochemistry confirmed no alteration in the number of microglia. Moreover, the results in hypoxia-treated primary spinal cord microglia confirmed the effect of FK-506 on TNF-a, IL-1b, and IL-6 expression and NF-κB activation. These findings suggest that FK-506 may be involved in microglial activation after SCI.

Upregulation of PSMB4 is Associated with the Necroptosis after Spinal Cord Injury.

Spinal cord injury (SCI) is one of the most common and severe complications in spine injury. It is difficult to prevent cell necroptosis and promote the survival of residual neurons after SCI. Proteasome beta-4 subunit (PSMB4) is the first proteasomal subunit with oncogenic properties promoting cancer cell survival and tumor growth in vivo, and our previous study showed that PSMB4 is significantly associated with neuronal apoptosis in neuroinflammation. However, PSMB4 function in the necroptosis after SCI is unkown. RIP3, a key regulatory factor of necroptosis, correlates with the induction of necroptosis in various types of cells and signaling pathway. Upregulation of the RIP3 expression may play a role as a novel molecular mechanism in secondary neural tissue damage following SCI. In this study, we established an acute spinal cord contusion injury model in adult rats to investigate the potential role of PSMB4 during the pathological process of SCI. We found PSMB4 expression was significantly up-regulated 3 days after injury by western blot and immunohistochemical staining. Double immunofluorescent staining indicated obvious changes of PSMB4 expression occurred in neurons. Significant up-regulation of PSMB4 expression was observed in Rip3 positive neurons at 3 days after SCI, which indicated that PSMB4 might play a vital role in the regulation of Rip3. Overexpress and knockdown PSMB4 could intervene the RIP3 and Mixed lineage kinase domain-like protein (MLKL) pathway in Tumor necrosis factor-α (TNF-α) induced necroptosis cell model. Based on our experimental data, we boldly conclude that PSMB4 is associated with RIP3 involved necroptosis after SCI.

The importance of EHD1 in neurite outgrowth contributing to the functional recovery after spinal cord injury

Traumatic spinal cord injury is one of the most common and severe problems for using NGF to promote the neurite outgrowth of survival neurons. EHD1 regulates and controls the endocytosis and transportation of neurotrophins and transmembrane cargo via recycling endosome for neurite outgrowth. TrkA is particularly considered to be a functional specific recepter in the cell membrane for NGF and is activated upon NGF binding. The transcytosis of TrkA is dependent on Rab11 recycling endosomes and is promoted by NGF signaling itself at the axon terminal. In this study, we established an acute spinal cord contusion injury model in adult rats to investigate the potential role of EHD1 during the pathological process of SCI. Western blot analysis suggested that EHD1 expression was low in the sham-operated adult rat spinal cords and was significantly up-regulated 1d after injury. Immunohistochemical staining detected the general distribution of EHD1 protein in both the gray and white matter of adult rat spinal cords. Double immunofluorescent staining indicated that EHD1 was expressed in neurons, astrocytes and microglias in the adult rat spinal cord, and obvious changes of EHD1 expression occurred in neurons during SCI pathological process. Significant up-regulation of EHD1 expression was observed in MAP2 positive neurons at 1 day after SCI, in comparison with the sham-operated control, which indicated that EHD1 might play a vital role in neurite outgrowth. Our data indicated that EHD1 could interact with TrkA, and is in the upstream of TrkA. EHD1 up-regulated the expression of TrkA in the glutamate stimulated primary neurons. Based on our experimental data, we boldly conclude that EHD1 regulates the recycling of TrkA back to cell membrane, improving the utilization efficiency of the NGF, which is vital for neurite outgrowth and functional recovery after spinal cord injury.

EGb761 improves histological and functional recovery in rats with acute spinal cord contusion injury.

This is an experimental study. The objective of this study was to evaluate the neuroprotective effects of Ginkgo biloba extract 761 (EGb761) on histological features of injured sites and on functional performance of rats subjected to standardized spinal cord injury (SCI). This study was conducted in Xian, Shaanxi, China. Thirty female Sprague-Dawley rats were randomly divided into three groups: sham-operated, saline-treated control and EGb761-treated. The Basso, Beattie, Bresnahan Locomotor Rating Score (BBB score) was calculated and footprint analysis was performed to evaluate the functional performance of the rats in each group. Hematoxylin and eosin (HE) staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and caspase-3 staining were performed to evaluate the necrosis area and apoptotic cells at the injured site in each group. At 14, but not 1, 3 and 7, days post injury (DPI), rats in the EGb761-treated group exhibited significantly better BBB scores compared with the saline-treated control group (P<0.05). The EGb761-treated group also showed increased stride length, decreased stride width and reduced toe dragging at 14 DPI (P<0.05). Analysis of HE staining revealed that the EGb761-treated group had reduced necrosis at the injury site compared with the saline-treated control group (P<0.05). Analysis of TUNEL and caspase-3 staining demonstrated that cell apoptosis was increased at 1-14 DPI, peaking at 24-h post injury in the gray matter, and 7 DPI in the white matter. At 7 DPI, the quantity of apoptotic cells was significantly decreased in the EGb761-treated group. EGb761 administration during the acute phase after SCI significantly reduced secondary injury-induced tissue necrosis and cell apoptosis and improved functional performance in rats.

Expression of Peroxiredoxin 1 After Traumatic Spinal Cord Injury in Rats

Reactive astrogliosis and microgliosis after spinal cord injury (SCI) contribute to glial scar formation that impedes axonal regeneration. The mechanisms underlying reactive astrocyte and microglia proliferation upon injury remain partially understood. Peroxiredoxin 1 (PRDX1) is an antioxidant participating in cell proliferation, differentiation, and apoptosis. However, PRDX1 functions in SCI-induced astrocyte and microglia proliferation are unknown. In this study, we established an acute spinal cord contusion injury model in adult rats to investigate the potential role of PRDX1 during the pathological process of SCI. We found the palpable expression increase of PRDX1 after SCI by western blot and immunohistochemistry staining. Double immunofluorescence staining showed that PRDX1 expression mainly increased in astrocytes and microglia. In addition, PRDX1/proliferating cell nuclear antigen (PCNA) colocalized in astrocytes and microglia. Furthermore, PCNA expression also elevated after SCI, as well as was positively correlated with PRDX1 expression. In vitro, PRDX1 expression in primary rat spinal cord astrocytes and microglia changed in a concentration- and time-dependent manner according to LPS treatment. In addition, PRDX1 knockdown in astrocytes and microglia resulted in the decrease of PCNA expression after LPS stimulation, showing that PRDX1 promoted astrocyte and microglia proliferation after inflammation. Our results suggested that PRDX1 might play a crucial role in astrocyte and microglia proliferation after SCI.

Temporospatial expression of fibulin-1 after acute spinal cord injury in rats

ObjectiveFibulin-1 is a matricellular protein that plays important roles in motility inhibition in a variety of cells and blocks the proliferation of cultured neural stem cells. The biological function of fibulin-1 in the spinal cord has not been fully elucidated.MethodsTo clarify the expressions and possible functions of fibulin-1 in spinal cord injury (SCI), we performed an acute spinal cord contusion injury model in adult rats. Our work studied the temporospatial expression patterns of fibulin-1.ResultsWestern blot analysis revealed that fibulin-1 levels significantly increased 5 days after spinal cord contusion. Immunohistochemistry confirmed an increased number of fibulin-1 immunopositive cells about 2 mm from the lesion site. Moreover, double immunofluorescence labeling suggested that these changes were especially prominent in neurons and microglia.ConclusionThese findings suggest that fibulin-1 may be involved in neuronal apoptosis and microglial activation after SCI.

Spatiotemporal pattern of TRAF3 expression after rat spinal cord injury.

TNF receptor associated factor 3 (TRAF3), a member of the TRAF family of intracellular signaling proteins, can directly influence the phosphorylation status and activation of c-Jun N-terminal kinase, participating in CD40-induced apoptosis in carcinoma. However, its expression profile and function are still unclear in spinal cord injury (SCI). In this study, we performed an acute spinal cord contusion injury model in adult rats and detected the dynamic change patterns of TRAF3 expression in spinal cord. Western blot and immunohistochemistry revealed a striking upregulation of TRAF3 after SCI. Double immunofluorescence staining prompted that TRAF3 immunoreactivity was found in neurons rather than astrocytes. Moreover, co-localization of TRAF3/active caspase-3 was detected in neuronal nuclei. To further investigate the function of TRAF3, a neuronal cell line PC12 was employed to establish an apoptosis model in vitro. We analyzed the association of TRAF3 with active caspase-3 on PC12 cells by western blot and immunofluorescent labeling, which was parallel with the data in vivo. Additionally, knocking TRAF3 down with siRNA demonstrated the probable pro-apoptotic role of TRAF3 in the process of neuronal apoptosis. To summarize, we firstly uncover the temporal and spatial expression changes of TRAF3 in SCI. Our data suggest that TRAF3 might be implicated in central nervous system pathophysiology after SCI.

LIN28 Expression in Rat Spinal Cord After Injury

LIN28, an RNA-binding protein, is known to be involved in the regulation of many cellular processes, such as embryonic stem cell proliferation, cell fate succession, developmental timing, and oncogenesis. However, its expression and function in central nervous system still unclear. In this study, we performed an acute spinal cord contusion injury (SCI) model in adult rats and investigated the dynamic changes of LIN28 expression in spinal cord. Western blot and immunohistochemistry analysis revealed that LIN28 was present in normal spinal cord. It gradually increased, reached a peak at 3 day, and then nearly declined to the basal level at 14 days after SCI. Double immunofluorescence staining showed that LIN28 immunoreactivity was found in neurons, astrocytes and a handful of microglia. Interestingly, LIN28 expression was increased predominantly in astrocytes but not in neurons. Moreover, the colocalization of LIN28 and proliferating cell nuclear antigen was detected after injury. Western blot showed that LIN28 participated in lipopolysaccharide (LPS) induced astrocytes inflammatory responses by NF-κB signaling pathway. These results suggested that LIN28 may be involved in the pathologic process of SCI, and further research is needed to have a good understanding of its function and mechanism.

Spatiotemporal Profile and Essential Role of RBM3 Expression after Spinal Cord Injury in Adult Rats

Hypoxia and other adverse conditions are usually encountered by rapidly growing cells. The RNA-binding motif protein 3 (RBM3) is induced by low temperature and hypoxia. However, its expression and function in spinal cord injury are still unclear. To investigate the certain expression and biological function in the central nervous system, we performed an acute spinal cord contusion injury (SCI) model in adult rats. Western blot analysis indicated a striking expression upregulation of RBM3 after spinal cord injury (SCI). Double immunofluorescence staining prompted that RBM3 immunoreactivity was found in astrocytes and neurons. Interestingly, RBM3 expression was increased predominantly in astrocytes. Furthermore, colocalization of RBM3 with proliferating cell nuclear antigen (PCNA) was detected in astrocytes. To further understand whether RBM3 plays a role in astrocyte proliferation, we applied lipopolysaccharide (LPS) to induce astrocyte proliferation in vitro. Western blot analysis demonstrated that RBM3 expression was positively correlated with PCNA expression following LPS stimulation. Immunofluorescence analysis showed that the expression of RBM3 was also changed following the stimulation of astrocytes with LPS, which was parallel with the data in vivo. Additionally, knocking RBM3 down with small interfering RNA (siRNA) demonstrated that RBM3 might play a significant role in the proliferation of astrocytes treated by hypoxia in vitro. These results suggest that RBM3 may be involved in the proliferation of astrocytes after SCI. To summarize, we firstly uncover the temporal and spatial expression changes of RBM3 in spinal cord injury. Our data suggest that RBM3 might be implicated in central nervous system pathophysiology after SCI.

Temporal–spatial expression of ENOLASE after acute spinal cord injury in adult rats

ENOLASE enzymes are abundantly expressed, cytosolic carbon–oxygen lyases known for their role in glucose metabolism. Recent accumulation of evidence revealed that, in addition to its glycolytic function, enolase is also associated with ischemia, hypoxia and to be a neurotrophic factor. To analysis the certain expression and biological function in central nervous system, we performed an acute spinal cord contusion injury model in adult rats. Western blot analysis indicated a marked upregulation of ENOLASE after spinal cord injury (SCI). Immunohistochemistry revealed wide distribution of enolase in spinal cord, including neurons and glial cells. Double immunofluorescent staining for proliferating cell nuclear antigen and phenotype-specific markers showed increases of enolase expression in proliferating microglia and astrocytes. Our data suggest that enolase may be implicated in the proliferation of microglia and astrocytes after SCI.

Spatiotemporal patterns of Gem expression after rat spinal cord injury

Gem is an atypical protein of the Ras superfamily that plays a role in regulating voltage-gated Ca2+ channels and cytoskeletal reorganization. To elucidate the certain expression and biological function in central nervous system (CNS), we performed an acute spinal cord contusion injury model in adult rats. Western blot analysis showed a marked up-regulation of Gem after spinal cord injury (SCI). Immunohistochemistry revealed wide distribution of Gem in spinal cord, including neurons and glial cells. Double immunofluorescent staining for proliferating cell nuclear antigen (PCNA) and phenotype-specific markers indicated increases of Gem expression in proliferating microglia and astrocytes. Our data suggest that Gem may be implicated in the proliferation of microglia and astrocytes after SCI.

FOXO3a/p27kip1 expression and essential role after acute spinal cord injury in adult rat

FOXO3a (Forkhead Class box O3a), as an important direct target of the phosphatidylinositol 3-kinase (PI3K)/protein B (Akt) pathway, which regulates the cell survival and the cell-cycle progression. Recent reports showed that FOXO3a could inhibit cell-cycle progression at the G1/S transition by controlling transcription of the cyclin-dependent kinase inhibitor p27(kip1) , which is also a key regulator of the mammalian neurogenesis. To elucidate the expression and role of FOXO3a in nervous system lesion and repair, we performed an acute spinal cord contusion injury (SCI) model in adult rats, which showed a temporal-spatial expression pattern of FOXO3a. Temporally, FOXO3a protein level significantly reduced day 3 after injury, and following FOXO3a down-regulation, p27(kip1) protein and mRNA levels were also decreased after injury. Spatially, decreased levels of FOXO3a and p27(kip1) were predominant in astrocytes, which were regenerating axons and largely proliferated after injury. Furthermore in vitro, Western blot analysis, RT-PCR, and immunofluorescence staining analysis demonstrated the relationship between FOXO3a and p27(kip1) in primary astrocytes. FOXO3a modulated the cell cycle by transcriptional regulation of p27(kip1) in astrocytes. Administration of the PI3K pharmacological inhibitor LY294002 abrogated this effect by regulating FOXO3a and p27(kip1) expression and subcellular localization. These results suggest that decreased levels of FOXO3a and p27(kip1) in spinal cord are involved in axonal regeneration and the proliferation of glial cells after SCI.

Expression of RBMX After Spinal Cord Injury in Rats

RBMX (RNA-binding motif gene, X chromosome) is a heterogeneous nuclear ribonucleoprotein that associates with the spliceosome, binds RNA, and influences alternative splicing. The gene encoding RBMX is located on chromosome Xq26 and is ubiquitously expressed. However, its expression and function in spinal cord injury are still unclear. In this study, we performed an acute spinal cord contusion injury (SCI) model in adult rats and investigated the dynamic changes of RBMX expression in spinal cord. Western blot and immunohistochemistry analysis revealed that RBMX was present in normal spinal cord. It gradually increased, reached a peak at 1 day, and then declined to basal levels at 14 days after spinal cord injury. Double immunofluorescence staining showed that RBMX immunoreactivity was found in neurons and astrocytes, but not in microglia. Interestingly, RBMX expression was increased predominantly in neurons and astrocytes. Moreover, colocalization of RBMX/proliferating cell nuclear antigen (PCNA) and RBMX/active caspase-3 was detected in GFAP and NeuN, respectively. We also examined the expression profiles of active caspase-3, bcl-2, Bax, and PCNA, whose changes were correlated with the expression profiles of RBMX. In conclusion, this is the first description of RBMX expression in spinal cord injury. Our results suggested that RBMX might play crucial roles in CNS pathophysiology after SCI.

Temporal and Spatial Expression of KIF3B after Acute Spinal Cord Injury in Adult Rats

The KIF3 subunit KIF3B was proved to be associated with mitosis. It has been known to be engaged in intracellular transport of neurons. To elucidate the certain expression and biological function in central nervous system, we performed an acute spinal cord contusion injury model in adult rats. Western blot analysis indicated a marked upregulation of KIF3B after spinal cord injury (SCI). Immunohistochemistry revealed wide distribution of KIF3B in spinal cord, including neurons and glial cells. Double immunofluorescent staining for proliferating cell nuclear antigen and phenotype-specific markers showed increases of KIF3B expression in proliferating microglia and astrocytes. Our data suggest that KIF3B may be implicated in the proliferation of microglia and astrocytes after SCI.

KPC1 Expression and Essential Role After Acute Spinal Cord Injury in Adult Rat

KPC1 (Kip1 ubiquitylation-promoting complex 1) is the catalytic subunit of the ubiquitin ligase KPC, which regulates the degradation of the cyclin-dependent kinase inhibitor p27(kip1) at the G1 phase of the cell cycle. To elucidate the expression and role of KPC1 in nervous system lesion and repair, we performed an acute spinal cord contusion injury (SCI) model in adult rats. Western blot analysis showed a significant up-regulation of KPC1 and a concomitant down-regulation of p27(kip1) following spinal injury. Immunohistochemistry and immunofluorescence revealed wide expression of KPC1 in the spinal cord, including expression in neurons and astrocytes. After injury, KPC1 expression was increased predominantly in astrocytes, which highly expressed PCNA, a marker for proliferating cells. Co-immunoprecipitation demonstrated increased interactions between p27(kip1) and KPC1 4 days after injury. To understand whether KPC1 plays a role in astrocyte proliferation, we applied LPS to induce astrocyte proliferation in vitro. Western blot analysis demonstrated that p27(kip1) expression was negatively correlated with KPC1 expression following LPS stimulation. Immunofluorescence analysis showed subcellular localizations of p27(kip1) and KPC1 were also changed following the stimulation of astrocytes with LPS. These results suggest that KPC1 is related to the down-regulation of p27(kip1); this event may be involved in the proliferation of astrocytes after SCI.

Hydrogen-Rich Saline Protects Against Spinal Cord Injury in Rats

In the present study, we examined the mechanisms of hydrogen-rich saline, a reported therapeutic antioxidant, in the treatment of acute spinal cord contusion injury. Male Sprague-Dawley rats were used to produce a standardized model of contuses spinal cord injury (125 kdyn force). Hydrogen-rich saline was injected intraperitoneally (5 ml/kg) immediately, and at 24 and 48 h after injury. All rats were sacrificed at 72 h after spinal cord injury (SCI). Apoptotic cell death, oxidative stress, inflammation, level of Brain derived neurotrophic factor (BDNF) were evaluated. In addition, locomotor behavior was assessed using the Basso, Beattice and Bresnahan (BBB) scale. We observed that administration of hydrogen-rich saline decreased the number of apoptotic cells, suppressed oxidative stress, and improved locomotor functions. Hydrogen-rich saline increased the release of BDNF. In conclusion, hydrogen-rich saline reduced acute spinal cord contusion injury, possibly by reduction of oxidative stress and elevation of BDNF.

Lack of robust neurologic benefits with simvastatin or atorvastatin treatment after acute thoracic spinal cord contusion injury

Although much progress has been made in the clinical care of patients with acute spinal cord injuries, there are no reliably effective treatments, which minimize secondary damage and improve neurologic outcome. The time and expense needed to establish de novo pharmacologic or biologic therapies for acute SCI has encouraged the development of neuroprotective treatments based on drugs that are already in clinical use and, therefore, have the advantage of a well-characterized safety and pharmacokinetic profile in humans. Statins are the most commonly prescribed class of lipid-lowering drugs, and recently, it has been recognized that statins also have powerful immunomodulatory and anti-inflammatory effects. This paper describes a series of experiments that were performed to evaluate the comparative neuroprotective effects of simvastatin and atorvastatin. We observed a promising signal of neurologic benefit with simvastatin in our first experiment, but in repeated attempts to replicate that effect in three subsequent experiments, we failed to reveal any behavioral or histologic improvements. We would conclude that simvastatin given orally or subcutaneously at doses previously reported by other investigators to be effective in different neurologic conditions does not confer a significant neurologic benefit in a thoracic contusion injury model (OSU Impactor) when administered with a 1-h delay in intervention. We contend that further preclinical investigation of atorvastatin and simvastatin is warranted before considering their translation into human SCI.