The protective effect of rifampicin on behavioral deficits, biochemical, and neuropathological changes in a cuprizone model of demyelination.

Multiple sclerosis (MS) is a disease of the central nervous system (CNS) in which both neuroinflammation and neurodegeneration play critical roles in the pathogenesis of the disease. A growing body of evidence indicates that some antibiotics have anti-inflammatory and neuroprotective properties. Rifampicin, commonly used for the treatment of mycobacteria, has been shown to exert neuroprotective activities in neurodegenerative diseases. In this study, we examined the efficacy of rifampicin on demyelination, gliosis, apoptosis, inflammation, behavioral dysfunction, and biochemical alterations in the cuprizone model of demyelination. For this aim, male C57BL/6J mice were fed a chow containing 0.2% cuprizone (w/w) for 6 weeks to induce reversible demyelination in the corpus callosum. Mice intraperitoneally received serial doses of rifampicin (10, 20, or 40 mg/kg body weight) in the last 7 days of a 6-week period of cuprizone treatment. The results showed that the administration of rifampicin led to the improvement in motor behavioral deficits. In line with this, rifampicin decreased the number of apoptotic cells in the corpus callosum thereby diminishing the expression of cleaved caspase-3 and Bax, as well as increasing Bcl-2. Moreover, rifampicin significantly lowered the levels of interleukin-6, interleukin-1ß, caspase-12 activity, heme oxygenase-1(HO-1), nitric oxide (NO), and malondialdehyde (MDA) in mice treated with cuprizone. Conversely, the activity of glutathione peroxidase (GPx) and the level of ferric reducing ability of plasma (FRAP) were increased in response to the treatment with rifampicin. Histopathological findings demonstrated that rifampicin statistically promoted remyelination and mitigated microgliosis and astrogliosis. It seems that rifampicin is able to be added to the armamentarium of therapies for multiple sclerosis.

The effect of minocycline on indolamine 2, 3 dioxygenase expression and the levels of kynurenic acid and quinolinic acid in LPS-activated primary rat microglia.

Microglia are one of the most important neural cells in the central nervous system (CNS) which account for 10-15% of all cells found in the brain. A vast majority of studies indicate that microglia play a pivotal role in protection and damage of the CNS. It has been shown that microglia are mainly scavenger cells but also produce a barrage of factors that are involved in tissue repair and neural regeneration. Several lines of evidence indicate that unregulated activation of microglia in response to either endogenous or exogenous insults results in the production of toxic factors that propagate neuronal injury. Studies demonstrated that the activated microglia secret the excessive amounts of quinolinic acid (QA) and kynurenic acid (KYNA) which are highly toxic for the neuronal cells. In line with this, indolamine 2, 3 dioxygenase (IDO), an enzyme producing KYNA and QA has been shown to be elevated during the inflammation in microglia. In this study, we established primary microglial cell cultures obtained from cerebral cortices of 1-day neonatal Wistar rats. Minocycline (20-60 µM) or its vehicle was added to the culture media 60 min prior to 48 h incubation with lipopolysaccharide (LPS; 10 ng/mL). Using a specific process of adhesion and shaking of the cultured glial cells, a purified culture of approximately 94% enriched microglia was obtained and then, corroborated by immunocytochemistry (ICC). The cell viability after minocycline treatments was assessed using the MTT colorimetric assay. The expression of IDO was evaluated using qPCR. The levels of KYNA and QA were determined using enzyme-linked immunosorbent assay (ELISA). The results showed that minocycline significantly decreased the levels of both KYNA and QA in glia cells exposed to LPS. Moreover, minocycline decreased the expression of IDO in treated LPS-induced microglia. It seems that minocycline has a potent ability to oppress the inflammatory process via the decrease in production of IDO expression and the concentrations of KYNA and QA.

Fabrication and characterization of gold nanoparticle-doped electrospun PCL/chitosan nanofibrous scaffolds for nerve tissue engineering.

In the field of nerve tissue engineering, nanofibrous scaffolds could be a promising candidate when they are incorporated with electrical cues. Unique physico-chemical properties of gold nanoparticles (AuNPs) make them an appropriate component for increasing the conductivity of scaffolds to enhance the electrical signal transfer between neural cells. The aim of this study was fabrication of AuNPs-doped nanofibrous scaffolds for peripheral nerve tissue engineering. Polycaprolactone (PCL)/chitosan mixtures with different concentrations of chitosan (0.5, 1 and 1.5) were electrospun to obtain nanofibrous scaffolds. AuNPs were synthesized by the reduction of HAuCl4 using chitosan as a reducing/stabilizing agent. A uniform distribution of AuNPs with spherical shape was achieved throughout the PCL/chitosan matrix. The UV-Vis spectrum revealed that the amount of gold ions absorbed by nanofibrous scaffolds is in direct relationship with their chitosan content. Evaluation of electrical property showed that inclusion of AuNPs significantly enhanced the conductivity of scaffolds. Finally, after 5 days of culture, biological response of Schwann cells on the AuNPs-doped scaffolds was superior to that on as-prepared scaffolds in terms of improved cell attachment and higher proliferation. It can be concluded that the prepared AuNPs-doped scaffolds can be used to promote peripheral nerve regeneration.

A Time Course Study of Different Methods of Extraneural Scar Induction in a Rat Model.

Background Extraneural scar formation is a challenging problem in nerve repair. Rodent models of scar induction, with their high regenerative capacity, suffer from lack of comparable similarities with human cases. In this study, we attempted to find a reliable and reproducible method of extraneural scarring with a significant impact on the peripheral nerve function. Methods A total of 60 rats were divided into three scar induction groups: abrasion (with a small piece of compressed steel wool), mincing (with extracorporeal mincing of adductor muscle and a 5-mm wide strip of the anterior border of the biceps femoris), and electrocoagulation (with a bipolar coagulator). Extraneural scarring was evaluated macroscopically and histologically during 8 weeks. The tibial functional index was used for behavioral analysis. Results Among three different physical methods of scar induction that were applied, electrocoagulation had the most functional impairment (p < 0.001, two-way analysis of variance); whereas mincing produced the most adhesive and intensive scar, morphologically (p < 0.001). Conclusion We conclude that: (1) the impact of the extraneural scar on the nerve is morphologically and functionally different, based on the method of scarring; (2) to achieve a scar model comparable to the human situation, a method in which the involved nerve is functionally impaired, is preferred over the ones that merely produce a bulky scar.

Nanoshell-mediated targeted photothermal therapy of HER2 human breast cancer cells using pulsed and continuous wave lasers: an in vitro study.

In this study, we report the apoptosis induction in HER2 overexpressed breast cancer cells using pulsed, continuous wave lasers and polyvinylpyrrolidone (PVP)-stabilized magneto-plasmonic nanoshells (PVP-MPNS) delivered by immunoliposomes. The immunoliposomes containing PVP-MPNS were fabricated and characterized. Heating efficiency of the synthesized nanostructures was calculated. The effect of functionalization on cellular uptake of nanoparticles was assessed using two cell lines of BT-474 and Calu-6. The best uptake result was achieved by functionalized liposome (MPNS-LAb) and BT-474. Also, the interaction of 514 nm argon (Ar) and Nd/YAG second harmonic 532-nm lasers with nanoparticles was investigated based on the temperature rise of the nanoshell suspension and the release value of 5(6)-carboxyfluorescein (CF) from CF/MPNS-loaded liposomes. The temperature increase of the suspensions after ten consecutive pulses of 532 nm and 5 min of irradiation by Ar laser were measured approximately 2 and 12 °C, respectively. The irradiation of CF/MPNS-loaded liposomes by Ar laser for 3 min resulted in 24.3 % release of CF, and in the case of 532 nm laser, the release was laser energy dependent. Furthermore, the comparison of CF release showed a higher efficiency for the Ar laser than by direct heating of nanoshell suspension using circulating water. The percentage of cell apoptosis after irradiation by Ar and 532 nm lasers were 44.6 and 42.6 %, respectively. The obtained results suggest that controlling the NP-laser interaction using optical properties of nanoshells and the laser parameters can be used to develop a new cancer therapy modality via targeted nanoshell and drug delivery.

Comparison of a new single-donor human fibrin adhesive with suture for posterior tibial nerve repair in rat: biomechanical resistance and functional analysis.

OBJECTIVE: The use of fibrin adhesives has a broad background in nerve repair. Currently the suboptimal physical properties of single- donor fibrin adhesives have restricted their usage. The present experiment studies the performance and physical characteristics of a modified fibrin glue prepared from single-donor human plasma in the repair of posterior tibial nerve of rat. METHODS: Forty Wistar rats were divided into 5 groups; in the control group, tibial nerve was completely transected and no treatment was done, while in the four experimental groups the nerve stumps were reconnected by one suture, three sutures, one suture with fibrin glue and fibrin glue alone respectively. During 8 weeks of follow-up, Tibial Function Index was measured weekly and adhesive strength, inflammation and scar formation were assessed at the end of the study. RESULTS: Nerve stumps dehiscence rate and adhesive strength were similar in all experimental groups and significantly differed from control group (P<0.05). By the end of the eighth follow-up week, functional recovery of one and three sutures groups were significantly higher than groups in which fibrin glue was used for repair (P<0.05). The amount of inflammation and scar tissue formation was similar among all groups. CONCLUSION: The study results show that the prepared single-donor fibrin adhesive has acceptable mechanical properties which could provide required adhesiveness and hold nerve stumps in the long term; yet, we acknowledge that more studies are needed to improve functional outcome of single donor fibrin adhesive repair.

Effect of bilateral median nerve excision on sciatic functional index in rat: an applicable animal model for autologous nerve grafting.

Autologous nerve graft is still the treatment of choice in peripheral nerve injury when end-to-end nerve repair is not possible. The sciatic nerve is the most widely used nerve in rat experimental studies. To assess the possibility of using the rat median nerve as a delayed animal autologous nerve graft model in nerve regeneration studies, the effect of median nerve excision on the sciatic functional index (SFI) was evaluated. Thirty rats were distributed into three equal groups: in the sciatic and median nerve excision (SMNE) group, 10 mm of the right sciatic nerve was excised and 5 mm of both median nerves were excised a week later; in the median nerve excision (MNE) group, 5 mm of both median nerves were excised (both sciatic nerves remained intact); in the control group, no intervention was performed. SFI was calculated before and after each intervention. There was no significant difference between mean SFI values calculated before and after median nerve excision in SMNE (-86.8 versus -88.4, P = 0.61) and MNE groups (-3.9 versus -3.3, P = 0.93). Therefore, it may be suggested that median nerve excision does not affect SFI measurements in intact and/or completely injured sciatic nerve, which may propose the median nerve as an autologous donor nerve graft model in rats.

Fabrication and in vitro evaluation of 3D composite scaffold based on collagen/hyaluronic acid sponge and electrospun polycaprolactone nanofibers for peripheral nerve regeneration.

Replacement of peripheral nerve autografts with tissue engineered nerve grafts will potentially resolve the lack of nerve tissue especially in patients with severe concomitant soft tissue injuries. This study attempted to fabricate a tissue engineered nerve graft composed of electrospun PCL conduit filled with collagen-hyaluronic acid (COL-HA) sponge with different COL-HA weight ratios including 100:0, 98:2, 95:5 and 90:10. The effect of HA addition on the sponge porosity, mechanical properties, water absorption and degradation rate was assessed. A good cohesion between the electrospun PCL nanofibers and COL-HA sponges were seen in all sponges with different HA contents. Mechanical properties of PCL nanofibrous layer were similar to the rat sciatic nerve; the ultimate tensile strength was 2.23 ± 0.35 MPa at the elongation of 35%. Additionally, Schwann cell proliferation and morphology on three dimensional (3D) composite scaffold were evaluated by using MTT and SEM assays, respectively. Rising the HA content resulted in higher water absorption as well as greater pore size and porosity, while a decrease in Schwann cell proliferation compared to pure collagen sponge, although reduction in cell proliferation was not statistically significant. The lower Schwann cell proliferation on the COL-HA was attributed to the greater degradation rate and pore size of the COL-HA sponges. Also, dorsal root ganglion assay showed that the engineered 3D construct significantly increases axon growth. Taken together, these results suggest that the fabricated 3D composite scaffold provide a permissive environment for Schwann cells proliferation and maturation and can encourage axon growth.

Inhibition of protein disulfide isomerase has neuroprotective effects in a mouse model of experimental autoimmune encephalomyelitis.

Endoplasmic reticulum (ER) stress is strictly linked to neuroinflammation and involves in the development of neurodegenerative disorders. Protein disulfide isomerase (PDI) is an enzyme that catalyzes formation and isomerization of disulfide bonds and also acts as a chaperone that survives the cells against cell death by removal of misfolded proteins. Our previous work revealed that PDI is explicitly upregulated in response to myelin oligodendrocyte glycoprotein (MOG)-induced ER stress in the brain of experimental autoimmune encephalomyelitis (EAE) mice. The significance of overexpression of PDI in the apoptosis of neural cells prompted us to study the effect of CCF642, efficient inhibitor of PDI, in the recovery of EAE clinical symptoms. Using this in vivo model, we characterized the ability of CCF642 to decrease the expression of ER stress markers and neuroinflammation in the hippocampus of EAE mice. Our observations suggested that CCF642 administration attenuates EAE clinical symptomsand the expression of ER stress-related proteins. Further, it suppressed the inflammatory infiltration of CD4 + T cells and the activation of hippocampus-resident microglia and Th17 cells. We reported here that the inhibition of PDI protected EAE mice against neuronal apoptosis induced by prolonged ER stress and resulted in neuroprotection.

Increased expression of endoplasmic reticulum stress-related caspase-12 and CHOP in the hippocampus of EAE mice.

The role of endoplasmic reticulum (ER) stress has been proposed in several neurodegenerative and autoimmune diseases and may contribute to neural apoptosis. The complex role of ER stress-mediated apoptosis introduces a novel angle on multiple sclerosis (MS) research. Nevertheless, the mechanisms through which ER stress intermediates apoptosis are not entirely understood. To this aim, we examined the expression of C/EBP homologous protein (CHOP), caspase-12, and protein disulfide isomerase (PDI) in mice with experimental autoimmune encephalomyelitis (EAE). We found the upregulated expression of CHOP, caspase-12, and PDI in the brain of EAE mice in comparison to healthy mice. Furthermore, immunofluorescent dual-label staining verified elevated levels of caspase-12/CHOP in astrocytes, oligodendrocytes, and microglia in the hippocampus section of EAE mice. This study highlighted the presence of ER stress and increased activation of caspase-12 in the hippocampus of mice in response to EAE induction. Higher levels of caspase-12/CHOP in hippocampal oligodendrocytes as compared with microglia and astrocytes denote that oligodendrocytes are particularly sensitive to ER-mediated apoptosis. In conclusion, the regulation of ER stress pathway would be beneficial for the survival of oligodendrocyte.

Treatment of chronic thoracic spinal cord injury patients with autologous Schwann cell transplantation: an interim report on safety considerations and possible outcomes.

Several experimental studies have introduced Schwann cell transplantation as a means of recovery in animal models of spinal cord injury (SCI). The reported promising results together with the availability of autologous sources for Schwann cells indicate Schwann cell transplantation as a possible treatment for SCI. To address the safety and feasibility concerns we report 1-year follow-up of four patients aged between 22 and 43 years who had stable chronic (28-80 months) spinal cord injury at mid-thoracic level and treated with autologous Schwann cell transplantation. Purified Schwann cells used for transplantation were acquired from autologous sural nerve and cultured without the use of any specific mitogenic or growth factors. The patients were evaluated by means of American Spinal Injury Association (ASIA) criteria, sphincter, sexual function and Magnetic Resonance Imaging assessments for 1 year after transplantation. None of the patients were found to have any adverse effects indicating transfer of infection, neurological deterioration or other related clinical problems. Of the four patients, only one patient with incomplete SCI showed motor and sensory improvement 1 year after transplantation with extensive and continuous rehabilitation. All the four patients experienced transient paresthesia or increased muscle spasm after transplantation. Magnetic Resonance (MR) images of the patients did not show any visible changes or pathological findings after 1 year. This preliminary report shows that autologous Schwann cell transplantation is generally safe for the selected number of SCI patients but it does not prove beneficial effects. Further safety and outcome studies are recommended.

Effect of decompression on complete spinal cord injury in rats.

To examine whether spinal cord decompression improves functional recovery and decreases lesion volumes in paraplegic (not paraparetic) rats and, if so, at what postoperative time it is most efficacious. The spinal cords of 63 female rats were compressed at T9 with Yasargil clips. Rats were assigned randomly to five different treatment groups of 3 s, 1 hr, 6 hr, 3 weeks, and 10 weeks. Locomotor behavior scoring was based on the Basso, Beattie, Bresnahan (BBB) Locomotor Rating Scale (Ohio State University, Columbus, OH) motor scores. Comparing five groups, the mean BBB was statistically higher in the 3-s group (P < 0.05). Comparison of progressive changes in BBB in each group revealed statistically meaningful improvement in the 3-s group, too. Spared surface area of spinal cord was 81.5 +/- 4.9% in 3-s group and 10.8 +/- 1.4% in the delayed groups of decompression (P = 0.039). Rats undergoing immediate decompression showed significantly better functional recovery and smaller lesion volumes.

Fabrication and characterization of electrospun laminin-functionalized silk fibroin/poly(ethylene oxide) nanofibrous scaffolds for peripheral nerve regeneration.

The peripheral nerve regeneration is still one of the major clinical problems, which has received a great deal of attention. In this study, the electrospun silk fibroin (SF)/poly(ethylene oxide) (PEO) nanofibrous scaffolds were fabricated and functionalized their surfaces with laminin (LN) without chemical linkers for potential use in the peripheral nerve tissue engineering. The morphology, surface chemistry, thermal behavior and wettability of the scaffolds were examined to evaluate their performance by means of scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and water contact angle (WCA) measurements, respectively. The proliferation and viability of Schwann cells onto the surfaces of SF/PEO nanofibrous scaffolds were investigated using SEM and thiazolyl blue (MTT) assay. The results showed an improvement of SF conformation and surface hydrophilicity of SF/PEO nanofibers after methanol and O2 plasma treatments. The immunostaining observation indicated a continuous coating of LN on the scaffolds. Improving the surface hydrophilicity and LN functionalization significantly increased the cell proliferation and this was more prominent after 5 days of culture time. In conclusion, the obtained results revealed that the electrospun LN-functionalized SF/PEO nanofibrous scaffold could be a promising candidate for peripheral nerve tissue regeneration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1595-1604, 2018.

Minocycline decreases CD36 and increases CD44 in LPS-induced microglia.

Microglia are the resident macrophages patrolling the central nervous system (CNS) to find dangerous signals and infectious agents mediating catastrophic cascades resulting in neuronal degeneration. Their morphological and biochemical properties made them enable to swift activation in response to neural insults and site-directed phagocytosis. Beside of beneficial roles in homeostasis of the brain and spinal cord, microglia can be participating in neuronal destruction and propagation of inflammation when they are unregulated or hyper-activated. A large body of research indicates that various cluster of differentiations (CDs) contribute to flame/quench the inflammatory processes occurred in immune system. In this study, we investigated the expression of CD36 and CD44 in LPS-activated primary rat microglia in response to treatment of minocycline at the levels of protein and gene using flow cytometry and real-time PCR, respectively. The results showed that minocycline decreased the expression of CD36 in cells treated with minocycline with respect to cells treated with LPS. Inversely, the expression of CD44 was increased in cells treated with minocycline in comparison to LPS-induced microglia. It seems that minocycline can modulate the expression of CDs involved in inflammatory reactions and enrich the armamentarium of therapeutic agents used for the treatment of neuroinflammatory and neurodegenerative disorders.

Transplantation of Schwann cells to subarachnoid space induces repair in contused rat spinal cord.

Schwann cell transplantation is well known to induce repair in the injured spinal cord which disables millions of injured patients throughout the world. An ideal route of delivering the grafted Schwann cells to the spinal cord should neither cause more injury nor reinitiate inflammatory events and also provide a favorable milieu to the grafted cells. In this study, we have utilized subarachnoid route to transplant Schwann cells and evaluated their effects in a contusive model of spinal cord injury. Adult rats weighing 100-140 g were experimentally injured by crushing the spinal cord with a titanium clip and then divided into four groups (Tracing, Control, Medium-treated and Schwann cell-treated). Cultured Schwann cells (5x10(4) cells in 5 microl) or medium were injected to the animals of corresponding groups via subarachnoid space at the injured site 7 days after injury. In tracing group, Schwann cells (labeled with Hoechst) demonstrated their presence within spinal cord 7 days after transplantation. Evaluation of locomotor performance of animals for 60 days after injury showed that animals treated with Schwann cells had significant improvement (P<0.01). Similarly, the axon density at the site of injury was significantly higher. The results indicate the efficacy of subarachnoid route for the transplantation of Schwann cells in inducing repair of the contused spinal cord. We conclude that this route can be useful for the transplantation of Schwann cells and offers a hope for the patients suffering from spinal cord injury.

Subarachnoid Space Transplantation of Schwann and/or Olfactory Ensheathing Cells Following Severe Spinal Cord Injury Fails to Improve Locomotor Recovery in Rats.

Treatment of spinal cord injury by exogenous cells has brought both successful and unsuccessful results. Olfactory ensheathing cells and Schwann cells have been widely used for transplantation purposes. In this study, we investigated the effects of these cells on contused spinal cord by introducing cells into subarachnoid space. Fifty thousand Schwann cells or olfactory ensheathing cells or a mixture of both cell types were transplanted one week after a 3-second clip compression injury at T-9 spinal cord level in rats. Starting from the day one of spinal cord injury, animals were assessed for six months by BBB test and then were sacrificed for immunohistochemistry labeling of the spinal cord injury site. There was no locomotor recovery in any of the treatment groups including controls. Immunohistochemistry assessment indicated positive labeling of P75 and S100 markers in the cell-transplanted groups compared with control. Our data suggest that transplantation of Schwann cells and/or olfactory ensheathing cells into the subarachnoid space does not improve motor recovery in severely injured spinal cord, at least with the number of cells transplanted here. This, however, should not be regarded as an essentially negative outcome, and further studies which consider higher densities of cells are required.

Two-Stage Nerve Graft in Severe Scar: A Time-Course Study in a Rat Model.

BACKGROUND: Peripheral nerve repair outcomes are suboptimal in the presence of severe soft tissue injury and excessive scarring paralleling the process in tendon reconstruction of the hand. Inspired by the advantages of the two-stage technique in tendon grafting and with encouraging preliminary results, we aimed to investigate the two-stage nerve grafting technique as an alternative method of secondary nerve repair. METHODS: Thirty female rats (~200 g) were randomly distributed into two groups (n=15). A 15 mm gap was created in the sciatic nerve of the animals and an excessive extraneural scar was induced using the "mincing" method. In this method, a thin strip of muscle was removed, minced in a petri dish and returned to the peripheral nerve. In the two-stage nerve graft group, a silicone tube was interposed in the first stage. After 4 weeks, in the second stage, the silicone tube was removed and a median nerve autograft was interposed through the newly formed vascularized sheath. In the conventional graft group, two nerve ends were protected with silicone caps in the first stage. After 4 weeks the caps were removed and the median graft was interposed. Behavioral assessments were performed at week 15 after surgery with the withdrawal reflex latency (WRL) and extensor postural thrust (EPT) and at the 3, 6 and 15-week time points with the TOA (toe out angle). Masson Trichrome staining method was used for histological assessments at week 15. RESULTS: According to the EPT and WRL, the two-stage nerve graft showed significant improvement (P=0.020 and P=0.017 respectively). The TOA showed no significant difference between the two groups. The total vascular index was significantly higher in the two-stage nerve graft group (P<0.001). CONCLUSIONS: Two-stage nerve graft using a silicone tube enhances vascularity of the graft and improves functional recovery.

The effects of picric acid (2,4,6-trinitrophenol) and a bite-deterrent chemical (denatonium benzoate) on autotomy in rats after peripheral nerve lesion.

Denervation of the hind limb is a technique used to study peripheral nerve regeneration. Autotomy or autophagia is an undesirable response to denervation in such studies. Application of a commercially available lotion used to deter nail biting in humans reduced autotomy in rats after denervation but did not completely prevent it. In this study, this authors evaluated the application of picric acid to prevent autotomy in rats in peripheral nerve experiments. They carried out sciatic nerve transection in 41 adult female Wistar rats and then applied either bite-deterrent lotion (n = 26) or saturated picric acid solution (n = 15) topically to the affected hind limb immediately after surgery and every day for 1 month. Autotomy scores were lower for rats treated with picric acid than for rats treated with bite-deterrent lotion 1 week and 2 weeks after surgery but were not different between the two groups 4 weeks after surgery. The authors conclude that application of picric acid could be used as an alternative strategy to prevent autotomy in peripheral nerve studies.

Comparison and evaluation of current animal models for perineural scar formation in rat.

UNLABELLED: Objective (s): Scar formation in injured peripheral nerve bed causes several consequences which impede the process of nerve regeneration. Several animal models are used for scar induction in preclinical studies which target prevention and/or suppression of perineural scar. This study evaluates the translational capacity of four of physical injury models to induce scar formation around the sciatic nerve of rat: laceration, crush, mince and burn. MATERIALS AND METHODS: Functional (Toe out angle), macroscopic, and microscopic evaluations were performed weekly for four weeks and correlation of findings were analyzed. RESULT: While macroscopic and microscopic findings suggested a well-developed and adhesive fibrosis surrounding the sciatic nerve, functional assessment did not reveal any significant difference between control and experimental groups (P>0.05). CONCLUSION: Our study suggests that none of the applied animal models reproduce all essential features of clinical perineural scar formation. Therefore, more studies are needed to develop optimal animal models for translating preclinical investigations.

The effect of timing of decompression on neurologic recovery and histopathologic findings after spinal cord compression in a rat model.

Prior animal models have shown that rats sustaining 3-second immediate spinal cord compression had significantly better functional recovery and smaller lesion volumes than rats subjected to compression times of 1 hour, 6 hours, 3 weeks, and 10 weeks after spinal cord injury. We compare locomotor rating scales and spinal cord histopathology after 3 seconds and 10 minute compression times. . Ten rats were assigned into two early (3-second) and late (10-minute) compressive surgery groups. Compressive injury was produced using an aneurysmal clip method. Rats were followed-up for 11 weeks, and behavioral assessment was done by inclined plane test and tail-flick reflex. At the end of the study, the rats were sacrificed, and spinal cord specimens were studied in light and EM. Basso, Beattie and Bresnahan (BBB) locomotor rating scales were significantly better in the early compression group after the 4th week of evaluation (P<0.05) and persisted throughout the remainder of the study. Histopathology demonstrated decreased normal tissue, more severe gliosis and cystic formation in the late group compared to the early group (P<0.05). In EM study, injuries in the late group including injury to the myelin and axon were more severe than the early compression group, and there was more cytoplasmic edema in the late compression group. Spinal cord injury secondary to 3-second compression improves functional motor recovery, spares more functional tissue, and is associated with less intracellular edema, less myelin and axon damage and more myelin regeneration in rats compared to those with 10 minutes of compression. Inclined plane test and tail-flick reflex had no significant difference.