Study of mouse induced pluripotent stem cell transplantation intoWistar albino rat cochleae after hair cell damage.

BACKGROUND/AIM: As the regeneration capacity of hair cells is limited, inner ear stem cell therapies hold promise. Effects of mouse induced pluripotent stem cells (IPSCs) on Wistar albino rats (WARs) with hearing impairment were investigated. MATERIALS AND METHODS: Thirty-five adult WARs with normal hearing were divided into 4 groups. Excluding the study group (n = 15), the other three groups served as control groups for ototoxicity and IPSC injection models. IPSC injections were performed via cochleostomy after a retroauricular approach. Auditory functions were evaluated with auditory brainstem responses (ABRs) before and after the injections. After a final hearing assessment the WARs were sacrificed and cochleae were extracted to see the biologic behavior of IPSCs in the inner ear by light microscopy and immunohistochemistry. RESULTS: There were no significant differences in the click-ABR thresholds in the study group after IPSC transplantation. The mean hearing threshold in the study group after ototoxic agent injection was 53.2 dB (10-90 dB). There was no significant difference between groups (P > 0.05) and no differentiated stem cells were observed immunohistochemically. CONCLUSION: Transplanted IPSCs did not show a therapeutic effect in this trial. We discuss potential pitfalls and factors affecting the therapeutic effect.

Comparison of Etanercept, Etomidate and Erythropoietin and Their Combinations in Experimentally-Induced Spinal Cord Injury.

AIM: The aim of this study was to compare the preventive effects of Etanercept, Etomidate, Erythropoietin and their combination in experimentally induced spinal cord trauma by clinical, histopathological, electrophysiological parameters and biochemical examination. MATERIAL AND METHODS: 85 healthy female Wistar-Albino rats were used in this study. Rats were divided 8 trauma groups that consisted of 10 rats for each, and 5 rats for the sham group. Laminectomy was performed under general anesthesia and the spinal cord was exposed with intact dura mater, and injury was created by the clip compression model. After the spinal cord injury, drugs were administered immediately intraperitoneally or subcutaneously. Except the sham group, all groups received drugs and were observed 24 or 72 hours. At the 72nd hour each group was anesthesized and somatosensorial evoked potentials (SEP) were recorded from the interarcuate ligament from the 2 vertebra proximal to the injured spinal cord and spinal cord tissue samples were taken for histopathological and biochemical evaluation. RESULTS: Etomidate groups showed a lower effect on spinal cord injury than etanercept and erythropoietin in terms of clinical, SEP and TNF-α. Etanercept and erythropoietin's neuroprotective effectiveness was shown alone or in combination treatments. More meaningful results were achieved with the use of erythropoietin and etanercept combination after spinal cord injury (SCI) than using erythropoietin alone. After SCI, highest Basso, Beattie, and Bresnahan (BBB) scores were achieved in the group which Etanercept and Erythropoietin applied together. CONCLUSION: The neuroprotective activity of etomidate was suspect. The neuroprotective effect of etanercept and erythropoietin after SCI was shown in individual and combined applications in this study. However, more experimental studies are needed for clinical use.

The use of autologous neurogenically-induced bone marrow-derived mesenchymal stem cells for the treatment of paraplegic dogs without nociception due to spinal trauma.

The aim of this study was to investigate the effects of percutaneous transplanted autologous neurogenically-induced bone marrow-derived mesenchymal stem cells (NIBM-MSCs) in paraplegic dogs without deep pain perception (DPP) secondary to external spinal trauma. Thirteen client owned dogs that had failed in improvement neurologically at least 42 days after conservative management, decompression and decompression-stabilization were included in the study. Each dog received two doses of autologous 5.0 × 106 NIBM-MSCs suspension, which were positive to 2',3'-Cyclic-nucleotide-3'-phosphodiesterase (CNPase) and Microtubule-associated protein 2 (MAP-2), as well as to Glial fibrillary acidic protein (GFAP) and beta III tubulin. The cells were injected into the spinal cord through the hemilaminectomy or laminectomy defects percutaneously with 21 days interval for 2 times. The results were evaluated using Texas Spinal Cord Injury Scale (TSCIS), somatosensory evoked potentials (SEP) and motor evoked potentials (MEP) at the admission time, cell transplantation procedures and during 2, 5, 7 and 12th months after the second cell transplantation. Improvement after cell transplantation in gait, nociception, proprioception, SEP and MEP results was observed in just 2 cases, and only gait score improvement was seen in 6 cases, and no improvement was recorded in 5 cases. All progresses were observed until 2nd month after the second cell transplantation, however, there was no improvement after this period. In conclusion, percutaneous transplantation of autologous NIBM-MSCs is a promising candidate modality for cases with spinal cord injury after spinal trauma and poor prognosis.

Imaging and surgical outcomes of spinal tumors in 18 dogs and one cat.

Clinical and magnetic resonance imaging (MRI) findings, histological appearances and surgical outcomes of 18 dogs and one cat with spinal tumors are presented. Medical records of the cases admitted for spinal disorders were reviewed, and cases of spinal tumors that were diagnosed by MRI and confirmed by histological examination were included in this study. T1 weighted, T2 weighted and contrast enhanced T1 weighted images were taken and interpreted to evaluate the spinal tumors. The tumors were diagnosed as: meningioma (n = 6), ependymoma (n = 1), nerve sheath tumor (n = 4), metastatic spinal tumor (n = 3), osteosarcoma (n = 2), osteoma (n = 1), rhabdomyosarcoma (n = 1), and nephroblastoma (n = 1). Thirteen cases underwent surgical operation and the remaining six cases were euthanized at the request of the owners. The neurological status of the surgical cases did not deteriorate, except for one dog that showed ependymoma in the early period after the operation. These results indicate the potential for surgical gross total tumor removal of vertebral tumors to provide better quality of life and surgical collection of histological specimens for definitive diagnosis. For effective case management, dedicated MRI examination is important to accurate evaluation of the spinal tumors, and surgical treatment is useful for extradural and intradural-extramedullary spinal tumors.

Intraspinal Transplantation of Autologous Neurogenically-Induced Bone Marrow-Derived Mesenchymal Stem Cells in the Treatment of Paraplegic Dogs without Deep Pain Perception Secondary to Intervertebral Disk Disease.

AIM: To investigate the effects of neurogenically-induced autologous bone marrow-derived mesenchymal stem cells (NIBM-MSCs) in paraplegic dogs without deep pain perception (DPP) secondary to intervertebral disk disease (IVDD). MATERIAL AND METHODS: Seven dogs which could not be improved neurologically with conventional treatment modalities were included in the study. All dogs were diagnosed by magnetic resonance imaging and surgically treated. Each dog received two times a suspension of autologous 5.0x106 NIBM-MSCs, which were positive to CNPase and MAP-2, as well as to GFAP and beta III tubulin into the spinal cord through the hemilaminectomy defect percutaneously, with a 21-day interval. RESULTS: Two months after cell transplantation, there were no changes except for 1 gait score improvement for 1 of the cases. At the 4th month, gait score had improved 1 score in 5 cases, and one score progress was recorded in proprioception and nociception in 1 case. In eight months-followed up 4 cases were evaluated by the same parameter; gait score had improved in 3 cases, and propriception improved in 2 cases, and nociception improved in 3 cases. CONCLUSION: Our findings suggest that utility of autologous NIBM-MSCs for cases with poor prognosis after IVDD can be a promising approach.

Protective effects of resveratrol on cisplatin-dependent inner-ear damage in rats.

Cisplatin is a common chemotherapeutic agent used in many solid and hematologic malignancies. The main unwanted effect of cisplatin is ototoxicity, for which no standard treatment has been reported. The present study examined the protective efficacy of resveratrol on cisplatin-dependent ototoxicity through an experimental model. Fifteen rats were randomized into three groups. Group 1 (control group) (n = 5) received intraperitoneal (i.p.) 15 mg/kg cisplatin; group 2 (resveratrol group) (n = 5) received i.p. 100 mg/kg resveratrol, followed by i.p. 15 mg/kg cisplatin; group 3 (n = 5) served as a vehicle group and received i.p. 1 ml dimethyl sulfoxide. All rats underwent the auditory brainstem response (ABR) test before and 72 h after the treatment. Pretreatment ABR values of the groups were not significantly different. The pretreatment hearing threshold values of the groups were 30 ± 6.60 and 28.5 ± 5.29 dB in groups 1 and 2, respectively (p > 0.05). The post-ABR-I and post-ABR-IV values were, respectively, 1.41 ± 0.18 and 5.83 ± 0.16 ms in the control subjects and 1.19 ± 0.22 and 4.58 ± 0.27 ms in the study group. The ABR-I and ABR-IV durations in rats treated with resveratrol were significantly shorter (p < 0.01). A comparison of threshold values shows that the resveratrol-treated rats had significantly lower values than the control rats. After cisplatin injection, ABR I-IV intervals were compared among the groups. The ABR I-IV interval duration was 4.42 ± 0.16 ms in the control group, while the resveratrol-treated rats showed a significantly shorter ABR I-IV interval duration of 3.49 ± 0.27 ms (p < 0.001). Resveratrol attenuated cisplatin-dependent inner-ear damage, as shown by the ABR-I, ABR-IV, ABR I-IV interval, and hearing threshold values. Our results suggest that this natural antioxidant may be effectively used in reducing the unwanted effects of cisplatin on the ear physiology of patients, particularly those undergoing chemotherapy.

Cystocele and rectal prolapse in a female dog.

A case of cystocele and prolapsed rectum is reported. The urinary bladder and rectum were repositioned and fixed by cystopexy, colposuspension, and colopexy concurrently. There was no recurrence after 3 months. This is the first report to describe cystocele in a young female dog never having been pregnant.

Cystocèle et prolapsus rectal chez une chienne. Un cas de cystocèle et de prolapsus rectal est signalé. La vessie urinaire et le rectum ont été repositionnés et réparés par cystopexie, par colposuspension et colopexie de manière concomitante. Il n'y a pas eu de récurrence après 3 mois. Il s'agit du premier rapport pour décrire la cystocèle chez une jeune chienne qui n'avait jamais eu de gestation.(Traduit par Isabelle Vallières).

Effect of granulocyte-colony stimulating factor on spinal cord tissue after experimental contusion injury.

The purpose of this study was to investigate the early effects of granulocyte-colony stimulating factor (G-CSF) on myeloperoxidase (MPO) activity, lipid peroxidation (LPO) and ultrastructural findings in rats after spinal cord injury (SCI). We also compared the effects of G-CSF and methylprednisolone sodium succinate (MPSS). Wistar rats were divided into four groups: control, SCI alone (50 g/cm weight drop trauma), SCI+MPSS (30 mg/kg), and SCI+G-CSF (50 µg/kg). Administration of G-CSF and MPSS significantly decreased LPO (p < 0.05) and MPO activity (p < 0.05) in the first 24 hours. MPSS was more effective than G-CSF in reducing LPO (p < 0.05) and in minimizing ultrastructure changes. The results of this study indicate that G-CSF exerts a beneficial effect by decreasing MPO activity and LPO and may reduce tissue damage in the first 24 hours after SCI. Our findings do not exclude the possibility that G-CSF has a protective effect on spinal cord ultrastructure after the first 24 hours following SCI.

Effects of raloxifene on cerebral vasospasm after experimental Subarachnoid Hemorrhage in rabbits.

BACKGROUND: The aim of this study was to investigate the ability of a SERM, RLX, to prevent vasospasm in a rabbit model of SAH. METHODS: Thirty-four New Zealand white rabbits were allocated into 3 groups randomly. Subarachnoid hemorrhage was induced by injecting autologous blood into the cisterna magna. The treatment groups were as follows: (1) sham operated (no SAH [n = 12]), (2) SAH only (n = 12), and (3) SAH plus RLX (n = 10). Basilar artery lumen areas and arterial wall thickness were measured to assess vasospams in all groups. RESULTS: There was a statistically significant difference between the mean basilar artery cross-sectional areas and the mean arterial wall thickness measurements of the control and SAH-only groups (P < .05). The difference between the mean basilar artery cross-sectional areas and the mean arterial wall thickness measurements in the RLX-treated group was statistically significant (P < .05). The difference between the SAH group and the SAH + RLX group was also statistically significant (P < .05). CONCLUSIONS: These findings demonstrate that RLX has marked vasodilatatory effect in an experimental model of SAH in rabbits. This observation may have clinical implications suggesting that this SERM drug could be used as possible anti-vasospastic agent in patients without major adverse effects.

Effects of carbamazepine on spinal cord ischemia.

BACKGROUND: Prophylactic treatment with carbamazepine has been shown to reduce the cerebral damage and neurologic deficit in ischemic conditions. A randomized controlled study based on a rabbit model was designed to study the effect of carbamazepine on a spinal cord ischemic reperfusion injury. METHODS: Thirty New Zealand rabbits were randomly assigned to 1 of the 2 groups (n = 15 per group): group I (control group) and group II (carbamazepine group). Spinal cord ischemia was induced by infrarenal aortic crossclamp for 25 minutes in both groups. Functional evaluation with the Tarlov score during a 2-day observation period and histopathologic assessment of the lumbar spinal cord were performed. Changes in spinal cord morphology were observed with hematoxylin-eosin staining and electron microscopy. Gray matter damage was assessed on the basis of the number of normal neurons in the ventral horn. RESULTS: Diffuse destruction of gray matter with moderate to severe vacuolization and essentially no normal ganglion cells was observed in the spinal cord of rabbits in the control group, whereas specimens of rabbits assigned to the carbamazepine group showed ganglion cells with normal nuclei and cytoplasm (P < .0001). Neurologic impairment was significantly attenuated in the carbamazepine group compared with the Tarlov scores of the control group (P < .0001 at day 2). CONCLUSION: Carbamazepine may protect the spinal cord from ischemic reperfusion injury that is associated with ameliorated neurologic and histopathologic results.

The role of extruded disk material in thoracolumbar intervertebral disk disease: a retrospective study in 40 dogs.

The objective of the study was to determine the effect of the dispersed or nondispersed form of the extruded disk material (EDM) on the neurological status and surgical outcomes in Hansen thoracolumbar intervertebral disk disease Type I (IVDD-I). Medical records of 40 dogs with IVDD-I were reviewed, including neurologic status on admission, findings on magnetic resonance imaging (MRI), intraoperative findings, and surgical outcomes. In MRI evaluations, EDM was on the right in 16, on the left in 18, and centrally in 6 cases; in all cases, findings were confirmed by surgery. Extruded disk material was localized and classified as dispersed disk (DD) or nondispersed disk (NDD) according to its dispersion in the epidural space on MRI. Twenty-five dogs had DD and 15 had NDD on both MRI and surgery. There was no significant difference between DD and NDD in preoperative neurological status and surgical outcomes (P > 0.05).