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Experimental animal study investigating the efficacy of C-terminal domain of tetanus toxin application as neuroprotective effects on rat brain in a model of spinal cord injury (SCI).The aim of the present study was to investigate the possible role of C-terminal domain of tetanus toxin (Hc-TeTx) on cell death mechanisms including apoptosis and autophagy following SCI.Traumatic SCI can lead to posttraumatic inflammation, oxidative stress, motor neuron apoptosis, necrosis, and autophagy of tissue. To promote and enhance recovery after SCI, recent development of devices and therapeutic interventions are needed.Twenty-eight adult rats were divided into four groups (n = 7 each) as follows: sham, trauma (SCI), SCI + Hc-TeTx, and SCI + methylprednisolone groups. The functional neurological deficits due to the SCI were assessed by behavioral analysis using the Basso, Beattie and Bresnahan (BBB) open-field locomotor test. The alterations in pro-/anti-apoptotic and autophagy related-protein levels were measured by Western blotting technique.In this study, Hc-TeTx promotes locomotor recovery and motor neuron survival of SCI rats. Hc-TeTx also decreased expression of bax, bad, bak, cleaved caspase-3, Ask1, and autophagy-related proteins including Atg5 and LC3II in brain. Our study provides an evidence that cell death mechanisms play critical roles in SCI and that the nontoxic peptides including Hc-TeTx may exert protective effect and decrease cell death following SCI.Our preliminary findings suggest a possible therapeutic agent to improve survival after spinal cord trauma, but further analysis are still needed to evaluate the difference between acute and chronic injuries.N/A.

Neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, and Huntington's disease affect millions of people in the world. Thus several new approaches to treat brain disorders are under development. The aim of the present study is to synthesize potential neuroprotective heterocyclic compounds based on pyrazolopyridine derivatives and then to evaluate their effects in MPP+-induced neurodegeneration in human neuroblastoma cell line (SH-SY5Y cells). The effects of the compounds on cell viability were measured by MTT assay and the changes in apoptosis-related proteins including bax, Bcl-2, Bcl-xl and caspase-3 were investigated by western blot technique. Based on the cell viability results obtained by MTT assay, the percentage of neuroprotection-induced by compounds against MPP+-induced neurotoxicity in SH-SY5Y cells was between 20% and 30% at 5 μM concentrations of all synthesized compounds. Moreover, the downregulation in pro-apoptotic proteins including bax and caspase-3 were found following the novel synthesized compounds treatments and these effects were observed in a dose-dependent manner. Our results provide an evidence that these heterocyclic compounds based on pyrazolopyridine derivatives may have a role on dopaminergic neuroprotection via antiapoptotic pathways.

The loss of neurons is strongly correlated with aging and aging-associated disorders. in this study, cell viability assays and mitochondrial function were performed to evaluate the effect of new spiro-pyrazole derivatives, prepared from aldehydes and 3-amino-1-phenyl-2-pyrazolin-5-one, on neuroprotection in an in vitro model of dopaminergic cell death induced by 1-methyl-4-phenylpyridinium (MPP+). The percentages of neuroprotection by derivatives were found between 21.26% and 52.67% at selected concentrations (10-50 mu M) with compound 4d exerting the best neuroprotective effect. The results show that the studied spiropyrazolones perform important roles in dopaminergic neuroprotection and can be used for potential new therapies in the treatment of neurodegenerative disorders including Parkinson's disease. (C) 2020 Elsevier Masson SAS. All rights reserved., University of AveiroEuropean Commission; Fundacao para a Ciencia e a Tecnologia (FCT, Portugal)/Ministerio da Ciencia, Tecnologia e Ensino Superior (MCTES, Portugal) [UIDB/50006/2020]; FEDER, within the PT2020 Partnership Agreement; Sultan Moulay Slimane University of Beni-Mellal (Morocco); National Center for Scientific and Technical Research (CNRST) -Morocco; FCT-CNRST (Morocco); FCTPortuguese Foundation for Science and TechnologyEuropean Commission [PD/BD/52531/2014], Thanks are due to the University of Aveiro and Fundacao para a Ciencia e a Tecnologia (FCT, Portugal)/Ministerio da Ciencia, Tecnologia e Ensino Superior (MCTES, Portugal) for the financial support for the LAQV-REQUIMTE (UIDB/50006/2020), through national founds and, where applicable, co-financed by the FEDER, within the PT2020 Partnership Agreement, and to the Portuguese NMR Network. The authors also thank the Sultan Moulay Slimane University of Beni-Mellal (Morocco) and the National Center for Scientific and Technical Research (CNRST) -Morocco for the funding the characterization analysis and to the Transnational cooperation programs, FCT-CNRST (Morocco), for financial assistance (2019-2020). C.M.B. Neves is also grateful to FCT for her Ph.D. Grant with the reference PD/BD/52531/2014. Authors also thank the Pharmaceutical Sciences Research Centre (FABAL, Ege University, Faculty of Pharmacy, Turkey) for equipmental support.

Recently, nuclear translocation and stability of nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) have gained increasing attention in the prevention of oxidative stress. The present study was aimed to evaluate the regulatory role of glycogen synthase kinase-3&beta, (GSK-3&beta, ) inhibition by tideglusib through the Nrf2 pathway in a cellular damage model. Gene silencing (siRNA-mediated) was performed to examine the responses of Nrf2-target genes (i.e., heme oxygenase-1, NAD(P)H:quinone oxidoreductase1) to siRNA depletion of Nrf2 in MPP+-induced dopaminergic cell death. Nrf2 and its downstream regulated genes/proteins were analyzed using Real-time PCR and Western Blotting techniques, respectively. Moreover, free radical production, the changes in mitochondrial membrane potential, total glutathione, and glutathione-S-transferase were examined. The possible contribution of peroxisome proliferator-activated receptor gamma (PPAR&gamma, ) to tideglusib-mediated neuroprotection was evaluated. The number of viable cells and mitochondrial membrane potential were increased following GSK-3&beta, enzyme inhibition against MPP+. HO-1, NQO1 mRNA/protein expressions and Nrf2 nuclear translocation significantly triggered by tideglusib. Moreover, the neuroprotection by tideglusib was not observed in the presence of siRNA Nrf2. Our study supports the idea that GSK-3&beta, enzyme inhibition may modulate the Nrf2/ARE pathway in cellular damage and the inhibitory role of tideglusib on GSK-3&beta, along with PPAR&gamma, activation may be responsible for neuroprotection.

Objective: In Psephellus and Centaurea genuses a lot of species have important pharmacological activities like antipyretic, antiinflamatory, diuretic, cytotoxic etc. In Psephellus genus the endemic plant Psephellus pyrrhoblepharus (Boiss.) Wagenitz (Centaurea pyrrhoblephara) was collected from Elazığ, Turkey. Recently interest in use of plant-derived compounds for therapeutic purposes in cancer is increasing day by day. Liver cancer which is one of the cancer types is affecting millions of people all over the world. So any approach to treat liver cancer is extremely valuable. Materials and methods: We have purposed to determine the cytotoxic activity of methanol:water (1:1), n-hexane and chloroform extracts of the aerial parts of P. pyrrhoblepharus using human liver cancer cell (HepG2) by utilizing the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay in different concentrations (50, 100 ,200 µg/ml) and time points (6, 12, 24 h). Results: Regarding the cytotoxicity, cell viability was seen as decreased following extract exposures at three different time points. The highest cytotoxic activity was observed in 100 µg/ml concentrations of chloroform extract at 24 h. At 12 h chloroform extract of plant showed the highest cytotoxic activity in 200 µg/ml concentrations when compared to methanol:water and n-hexane extracts. Conclusion: It can be suggested that extracts of P. pyrrhoblepharus show dose-dependent and time-dependent cytotoxic effects in HepG2 carsinoma cells. In general, the results provide information about the threshold concentrations of P. pyrrhoblepharus extracts that might be used in different applications without the risk of toxicity., Amaç: Birçok Psephellus ve Centaurea türü antipiretik, antiinflamatuar, diüretik ve sitotoksik gibi önemli farmakolojik aktivitelere sahiptir. Endemik bir bitki olan Psephellus pyrrhoblepharus (Boiss.) Wagenitz, Elazığ, Türkiye’den toplanmıştır. Son günlerde kanserde terapötik amaçlar için bitki kaynaklı bileşiklerin kullanımına olan ilgi artmaktadır. Bir kanser türü olan karaciğer kanseri de tüm dünyada milyonlarca insanı etkilemekteyken, karaciğer kanserini tedavi etmek için herhangi bir yaklaşım son derece değerlidir. Bu çalışmada, insan karaciğer kanseri hücresi (HepG2) kullanılarak P. pyrrhoblepharus bitkisinin topraküstü kısımlarından hazırlanmış olan metanol:su (1:1), kloroform ve n-hekzan ekstrelerinin sitotoksik potansiyelini değerlendirilmesi amaçlanmıştır. Gereç ve yöntemler: 3-(4,5-dimetiltiyazol-2-il)-2,5-difenltetrazolyumbromit (MTT) metodu kullanılarak, insan karaciğer kanser hücre hatlarında (HepG2) farklı konsantrasyonlarda (50, 100, 200 ug/ml) MTT, farklı zaman noktalarında (6, 12, 24 s) çalışmalar gerçekleştirildi. Bulgular: Sitotoksisite ile ilgili olarak, farklı zaman noktalarında ekstrelerin maruziyetlerinin ardından hücre canlılığının azaldığı gözlenmiştir. Bununla birlikte, en yüksek sitotoksik aktivite, 24 saatte 100 ug/ml konsantrasyondaki kloroform ekstresinde gözlenmiştir. Bitkinin kloroform ekstresi, metanol:su ve n-hekzan ekstreleri ile karşılaştırıldığında 12 saatte 200 ug/ml konsantrasyonda en yüksek sitotoksik etkinliği göstermiştir. Sonuç: P. pyrrhoblepharus ekstrelerinin HepG2 karsinoma hücrelerinde doza ve zamana bağlı bir şekilde sitotoksik etki gösterdiği ileri sürülebilir. Genel olarak elde edilen sonuçlar, toksisite tehlikesi olmadan farklı uygulamalarda kullanılabilecek P. pyrhoblepharus ekstrelerinin eşik konsantrasyonları hakkında bilgi sağlamıştır.

Spinal cord injury (SCI) leads to vascular damage and disruption of blood-spinal cord barrier which participates in secondary nerve injury. Epidermal growth factor (EGF) is an endogenous protein which regulates cell proliferation, growth and differention. Previous studies reported that EGF exerts neuroprotective effect in spinal cord after SCI. However, the molecular mechanisms underlying EGF-mediated protection in different regions of nervous system have not shown yet. In this study, we aimed to examine possible anti-apoptotic and protective roles of EGF not only in spinal cord but also in brain following SCI. Twenty-eight adult rats were divided into four groups of seven animals each as follows: sham, trauma (SCI), SCI + EGF and SCI + methylprednisolone (MP) groups. The functional neurological deficits due to the SCI were assessed by behavioral analysis using the Basso, Beattie and Bresnahan (BBB) open-field locomotor test. The alterations in pro-/anti-apoptotic protein levels and antioxidant enzyme activities were measured in spinal cord and frontal cortex. In our study, EGF promoted locomotor recovery and motor neuron survival of SCI rats. EGF treatment significantly decreased Bax and increased Bcl-2 protein expressions both in spinal cord and brain when compared to SCI group. Moreover, antioxidant enzyme activities including catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) were increased following EGF treatment similar to MP treatment. Our experiment also suggests that alteration of the ratio of Bcl-2 to Bax may result from decreased apoptosis following EGF treatment. As a conclusion, these results show, for the first time, that administration of EGF exerts its protection via regulating apoptotic and oxidative pathways in response to spinal cord injury in different regions of central nervous system.

Although hyperbaric oxygen (HBO) treatment following spinal cord injury (SCI) have been studied in terms of neurological function and tissue histology, there is a limited number studies on spinal cord tissue enzyme levels.The effect of HBO treatment in SCI was investigated by measuring superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), nitric oxide synthase (NOS) and nitric oxide (NO) activity in the injured tissue. SCI was induced by applying an aneurysm clip extradurally at the level of T9-T11 vertebrae. Preoperative HBO (preopHBO) treatment was applied for 5days and postoperative HBO (postopHBO) for 7days.In the preopHBO group, a significant decrease was observed in NOS and NO compared to the SCI group. There was a decrease in SOD, NOS and NO in the postopHBO group when compared to the SCI group. In the pre-postHBO group SOD, GPx, NOS and NO decreased significantly. There was a decrease in SOD in postopHBO compared to preopHBO. In the prepostopHBO, SOD decreased significantly compared to that in the preopHBO group. The prepostopHBO presented a significant decrease in GPx compared to postopHBO (p0.05 for all parameters). No significant difference was observed for catalase for all groups. Significant improvement was found in BBB scores for both postopHBO and prepostHBO groups when compared to the SCI group (p0.05).HBO treatment was found to be beneficial following SCI in terms of biochemical parameters and functional recovery in the postoperative period.

We investigated functional recovery of the lower urinary system in rats with spinal cord injury after transplanting neuronal restricted precursors/glial restricted precursors or neural cells derived from bone marrow stromal cells into the injured area of the spinal cord.A total of 30 rats underwent experimentation in 4 groups, including group 1--sham operation, group 2--spinal cord injury plus neuronal restricted precursor/glial restricted precursor transplantation, group 3--spinal cord injury plus bone marrow stromal cell transplantation and group 4--spinal cord injury control. All rats in the 4 groups were investigated urodynamically and sacrificed on day 28 after transplantation. The cells transplanted into the injured spinal cord underwent histological investigation.Transplanted cells (neuronal and glial restricted precursors, and bone marrow stromal cells) were found to maintain a presence in the injured spinal cord area. Baseline pressure, maximum capacity, mean uninhibited contraction amplitude, mean voiding pressure, voided volume and post-void residual volume were significantly better in groups 2 and 3 than in group 4, while baseline pressure in group 2 was better than that in group 3. We found no significant difference among the groups according to mean uninhibited contraction frequency.Although neuronal/glial restricted precursor transplanted rats seemed to have more improvement, all rats in groups 2 and 3 showed some significant improvement in lower urinary system function. On the other hand, the level of this improvement was far from complete functional recovery.

We explored the effects of early and late application of botulinum-A toxin (BTX-A) on reservoir function and histological bladder changes in spinal cord injured rats.The study was done in 30 Sprague-Dawley rats randomly allocated into 5 groups. Group 1 of 6 rats underwent sham operation only. Group 2 of 6 rats underwent spinal cord transection. Group 3 of 6 rats underwent spinal cord transection followed by BTX-A application into the detrusor muscle 7 days later. Group 4 of 6 rats underwent spinal cord transection, followed by BTX-A application into the detrusor muscle 28 days later. Group 5 of 6 rats underwent spinal cord transection followed by saline injection into the detrusor muscle after 28 days. Spinal cord injury was created by transecting the cord at the T9 to T10 level. All rats underwent cystometric examination initially and on day 42 before sacrifice. The bladders were removed and examined histologically for fibrosis and hyperplasia.On cystometric examination BTX-A caused an improvement in baseline pressure, and the frequency and amplitude of uninhibited detrusor contractions (p0.001). No significant differences were observed in maximal bladder capacity or urethral opening pressure (p0.05). Histologically BTX-A led to decreased fibrosis and hyperplasia (p0.001). No significant differences were found between histological or cystometric among the groups with respect to receiving BTX-A in the early and late periods (p0.05).BTX-A has a functional and histological healing effect on detrusor hyperreflexia subsequent to spinal cord injury in rats. Although administering BTX-A in the early period had better quantifiable functional and histological outcomes compared to the late period, the difference was not statistically significant.

Meconium aspiration syndrome (MAS) frequently results in inactivation of surfactant, persistent pulmonary hypertension (PPHN) and respiratory failure among newborn infants. Inflammation and inflammatory mediators play an important role in MAS. Since alveolar macrophages are thought to be very important cells in the pathogenesis of various inflammatory diseases, we evaluated whether meconium could stimulate rat alveolar macrophages to generate platelet-activating factor (PAF) and tumor necrosis factor (TNF)-alpha in vitro. We also examined the response to A23187 (calcium ionophore), 1-0-Hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (synthetic PAF) and dexamethasone on meconium-induced release of PAF and TNF-alpha. PAF and TNF-alpha concentrations from supernatant fluid were measured after high-performance liquid chromatography purification by specific radioimmunoassay, and TNF-alpha concentrations were determined by using an enzyme-linked immunosorbent assay. Our results showed that alveolar macrophages exposed to meconium could enhance PAF and TNF-alpha production in a dose (0.1, 1, 5 and 10%, P

Systemic kainic acid (KA) administration to rats triggers wet dog shakes (WDS) followed by epileptic seizures. Although WDS are often associated with the occurrence of seizures, we have recently shown that following nitric oxide (NO) synthesis inhibition, the number of WDS decreased; subsequently the onset of seizure activity was shortened, and the number of convulsions was increased. Somatostatin (SS), whose release appears to be controlled by NO, inhibits seizure activity. There are sex differences in seizure susceptibility as well as in SS and NO activities in brain. The present study was undertaken to assess the effect of octreotide (OC), a stable SS analogue, on KA-induced WDS and seizures in rats, with emphasis on possible sex differences. WDS and seizures were induced by KA in male and female (proestrus) Sprague Dawley rats; OC or saline was injected 30 min before KA and the behavior was monitored for 120 min after KA. Octreotide increased the number of WDS and decreased the number of convulsions; this effect was more pronounced in males. Onset of KA-induced seizure activity was earlier in females than males; however, there was no effect of OC on seizure latency. Seizure activity started after the termination of WDS. These results show OC has opposite effects on WDS and convulsions, in that it stimulates the former and inhibits the latter. These results support our previous findings that WDS and seizure activity involve separate mechanisms and suggest that WDS may have an inhibitory effect on limbic seizures.

Traumatic spinal cord injury (SCI) can lead to post-traumatic inflammation, oxidative stress, motor neuron apoptosis, necrosis and autophagy of tissue. To promote and enhance recovery after SCI, recent development of devices and therapeutic interventions are needed. The aim of the present study was to investigate the possible role of C-terminal domain of tetanus toxin (Hc-TeTx) on cell death mechanisms including apoptosis and autophagy following SCI. Thirty five adult rats were divided into five groups (n=7 each) as follows: control, sham, trauma (SCI), SCI+Hc-TeTx and SCI+methylprednisolone groups. The functional neurological deficits due to the SCI were assessed by behavioral analysis using the BBB open-field locomotor test. The alterations in pro-/anti-apoptotic and autophagy related-protein levels were measured by western blotting technique. In our study, Hc-TeTx promotes locomotor recovery and motor neuron survival of SCI rats. Hc-TeTx decreased expression of bax, bad, bak, cleaved caspase-3, Ask1 and autophagy-related proteins including Atg5 and LC3II in brain. Our study provides an evidence that cell death mechanisms play critical roles in SCI and non-toxic peptides may exert protective effect and decrease cell death following SCI.

Currently, hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide. However, the studies focusing on molecular etiology of HCC are limited. The Nrf2 signaling pathway can protect cells from a variety of toxicants and carcinogens by increasing the expression of a number of cytoprotective genes.The idea of using G. lucidum for cancer treatment is based on numerous laboratory and preclinical studies with cancer and immune cells as well as animal models demonstrating various biological activities in vitro and in vivo. The aim of our study is to evaluate the potential antioxidant role of G. lucidum in HCC. For this purpose, analysis of Nrf2 levels and cell cycle arrest were done. The most effective concentration of G. lucidum were found at 1/5 dilution. The changes in cytoplasmic/nuclear Nrf2 protein levels following G. lucidum extracts (1:5 or 1:10) treatments for 24, 48 or 72 h were observed. 1/10 and 1/5 diluted of G. lucidum induced G0/G1 cell cycle arrest in HCC. Consistently, the cells distributed in S phase were significantly reduced.In conclusion, our findings suggest that G. lucidum has a potential as an anticancer agent and. our data support the importance of the clarification of the molecular mechanisms of phytochemicals-induced Nrf2 activation.

Aims The aim of this study is to determine the role of nitric oxide (NO) in neuropathic pain and the effect of embryonic neural stem cell (ENSC) transplantation on NO content in rat spinal cord neurons following spinal cord injury (SCI). Main methods Ninety adult male Sprague–Dawley rats were divided into 3 groups (n = 30, each): control (laminectomy), SCI (hemisection at T12–T13 segments) and SCI + ENSC. Each group was further divided into sub-groups (n = 5 each) based on the treatment substance (L-NAME, 75 mg/kg/i.p.; l -arginine, 225 mg/kg/i.p.; physiological saline, SF) and duration (2 h for acute and 28 days for chronic groups). Pain was assessed by tail flick and Randall–Selitto tests. Fos immunohistochemistry and NADPH-d histochemistry were performed in segments 2 cm rostral and caudal to SCI. Key findings Tail-flick latency time increased in both acute and chronic L-NAME groups and increased in acute and decreased in chronic l- arginine groups. The number of Fos (+) neurons decreased in acute and chronic L-NAME and decreased in acute l -arginine groups. Following ENSC, Fos (+) neurons did not change in acute L-NAME but decreased in the chronic L-NAME groups, and decreased in both acute and chronic l -arginine groups. NADPH-d (+) neurons decreased in acute L-NAME and increased in l -arginine groups with and without ENSC transplantation. Significance This study confirms the role of NO in neuropathic pain and shows an improvement following ENSC transplantation in the acute phase, observed as a decrease in Fos(+) and NADPH-d (+) neurons in spinal cord segments rostral and caudal to injury.

Introduction Erectile dysfunction is common among patients with spinal cord injury (SCI). Aim This study aims to investigate the recovery of penile erectile functions of the rats with spinal cord injury (SCI) following transplantation of endogenous neuronal precursors cell (neuronal restricted precursors [NRP]/glial restricted precursors [GRP]) into the injured area of spinal cord. Methods Twenty‐two rats were experimented in three groups. Group 1 (N = 6): Sham; Group 2 (N = 10): SCI + NRP/GRP transplanted in day 9 after operation; Group 3 (N = 6): SCI + culture medium transplanted in day 9 after operation. Analysis of penile reflexes and cavernosal nerve stimulation studies were performed in day 28 after transplantation for each group. All rats in three groups were then sacrificed and the injured regions of spinal cords underwent histological investigation. Main Outcome Measures These results show improvements to some extent in locomotor and erectile functions although these improvements are far from full functional recovery. Results Cavernosal nerve stimulation resulted in significantly higher intracavernosal pressure in Group 3 (SCI) although there was no difference between Group 1 (sham) and Group 2 (SCI + NRP/GRP). Number of clusters was similar between groups. Number of erections was higher in Group 3 (SCI) than Groups 1 and 2, and number of cups was higher in Group 2 (SCI + NRP/GRP) than the other two groups. Number of flips was similar in Groups 1 and 2 but lower in Group 3. Number of long flips was highest in Group 1 and lowest in Group 3. The differences between groups were significant. Conclusion. This study emphasized the healing potential of NRP/GRP transplantation following experimental SCI. However, further experimental and clinical studies are required to advance this treatment modality. Temeltas G, Dagci T, Evren V, and Lekili M. Effects of neuronal and glial restricted precursor cells transplantation on erectile function after experimentally induced spinal cord injury.

WOS: 000268125600014, PubMed ID: 18637713, The oxidative mechanisms of injury-induced damage of neurons within the spinal cord are not very well understood. We used a model of T8-T9 spinal cord injury (SCI) in the rat to induce neuronal degeneration. In this spinal cord injury model, unilateral avulsion of the spinal cord causes oxidative stress of neurons. We tested the hypothesis that apurinic/apyrimidinic endonuclease (or redox effector factor-1, APE/Ref-1) regulates this neuronal oxidation mechanism in the spinal cord region caudal to the lesion, and that DNA damage is an early upstream signal. The embryonic neural stem cell therapy significantly decreased DNA-damage levels in both study groups-acutely (followed up to 7 days after SCI), and chronically (followed up to 28 days after SCI) injured animals. Meanwhile, mRNA levels of APE/Ref-1 significantly increased after embryonic neural stem cell therapy in acutely and chronically injured animals when compared to acute and chronic sham groups. Our data has demonstrated that an increase of APE/Ref-1 mRNA levels in the caudal region of spinal cord strongly correlated with DNA damage after traumatic spinal cord injury. We suggest that DNA damage can be observed both in lesional and caudal regions of the acutely and chronically injured groups, but DNA damage is reduced with embryonic neural stem cell therapy.

Object. Spinal cord injury (SCI) is a complex pathological entity, the treatment of which requires a multipronged approach. One way to integrate different therapeutic strategies for SCI is to develop implantable scaffolds that can deliver therapies in a synergistic manner. Many investigators have developed implantable “bridges,” but an important property of such scaffolds—that is, mechanical compatibility with host tissues—has been neglected. In this study, the authors evaluated the results of implanting a mechanically matched hydrogel-based scaffold to treat SCI. Methods. A nonbiodegradable hydrogel, poly(2-hydroxyethylmethacrylate) (PHEMA), was engineered using thermally initiated free radical solution polymerization. Two groups of 12 adult Sprague—Dawley rats underwent partial cervical hemisection injury followed by implantation of either PHEMA or PHEMA soaked in 1 µg of brain-derived neurotrophic factor (BDNF). Four rats from each group were killed 1, 2, or 4 weeks after induction of the injury. Immunofluorescence staining was performed to determine the presence of scarring, cellular inflammatory responses, gliosis, angiogenesis, and axonal growth in and around the implanted scaffolds. Conclusions. The implanted PHEMA with 85% water content had a compressive modulus of 3 to 4 kPa, which matched the spinal cord. Implanted PHEMA elicited modest cellular inflammatory responses that disappeared by 4 weeks and minimal scarring was noted around the matrix. Considerable angiogenesis was observed in PHEMA, and PHEMA soaked in BDNF promoted axonal penetration into the gel. The authors conclude that mechanically engineered PHEMA is well accepted by host tissues and might be used as a platform for sustained drug delivery to promote axonal growth and functional recovery after SCI.