Effects Of Systemic Administration Research Articles

The effect of systemic administration of salicylate on the auditory cortex of guinea pigs

To investigate the effect of systemic administration of salicylate as a tinnitus inducing drug in the auditory cortex of guinea pigs. Extracellular recording of spikes of the primary auditory cortex and dorsocaudal areas in healthy male albino Hartley guinea pigs was continuously performed (pre- and post-salicylate). We recorded 160 single units in the primary auditory cortex from five guinea pigs and 156 single units in the dorsocaudal area from another five guinea pigs. The threshold was significantly elevated after the administration of salicylate in both the primary auditory cortex and dorsocaudal areas. The Q10dB value was significantly increased in the primary auditory cortex, whereas it has significantly decreased in the dorsocaudal area. Spontaneous firing activity was significantly decreased in the primary auditory cortex, whereas it has significantly increased in the dorsocaudal area. Salicylate induces significant changes in single units of both stimulated and spontaneous activity in the auditory cortex of guinea pigs. The spontaneous activity changed differently depending on its cortical areas, which may be due to the neural elements that generate tinnitus.

Information capacity and robustness of encoding in the medial prefrontal cortex are modulated by the bioavailability of serotonin and the time elapsed from the cue during a reward-driven task

Serotonin (5-HT) is a key neuromodulator of medial prefrontal cortex (mPFC) functions. Pharmacological manipulation of systemic 5-HT bioavailability alters the electrical activity of mPFC neurons. However, 5-HT modulation at the population level is not well characterized. In the present study, we made single neuron extracellular recordings in the mPFC of rats performing an operant conditioning task, and analyzed the effect of systemic administration of fluoxetine (a selective serotonin reuptake inhibitor) on the information encoded in the firing activity of the neural population. Chronic (longer than 15 days), but not acute (less than 15 days), fluoxetine administration reduced the firing rate of mPFC neurons. Moreover, fluoxetine treatment enhanced pairwise entropy but diminished noise correlation and redundancy in the information encoded, thus showing how mPFC differentially encodes information as a function of 5-HT bioavailability. Information about the occurrence of the reward-predictive stimulus was maximized during reward consumption, around 3 to 4 s after the presentation of the cue, and it was higher under chronic fluoxetine treatment. However, the encoded information was less robust to noise corruption when compared to control conditions.

Localised Gingival Overgrowth in Patient taking Amlodipine

Gingival enlargement is an increase in the size of gingiva. It is one of the side effects of systemic administration of antihypertensives, anticonvulsants, and immunosuppressants. Amlodipine, a new third-generation dihydropyridine, very useful in middle-aged to older aged patients for various cardiovascular conditions can cause gingival enlargement. Treatment modalities for drug induced gingival enlargement include removal of local irritating factors, meticulous plaque removal and drug substitution after consultation with a physician. This article reports an amlodipine induced gingival enlargement and its treatment in a 40 years old hypertensive male patient.

Phase-I trial of survivin inhibition with EZN-3042 in dogs with spontaneous lymphoma

BackgroundLymphoma is a common cancer in dogs. While most dogs receiving chemotherapy experience remission, very few are cured, and median survival times are generally in the 12-month range. Novel approaches to treatment are unquestionably needed. The Inhibitor of Apoptosis Protein (IAP) family member survivin, which is one of the most commonly overexpressed proteins in human cancer, plays a key role in apoptosis resistance, a major cause of drug-resistant treatment failure. Survivin targeting therapies have shown promise preclinically; however, none have been evaluated in dogs to date. The goal of the current study was to determine the safety and pharmacodynamic effects of systemic administration of the anti-survivin locked nucleic acid antisense oligonucleotide EZN-3042 in dogs with lymphoma.ResultsWe performed a prospective phase-I clinical trial in dogs with biopsy-accessible peripheral nodal lymphoma. Eighteen dogs were treated with EZN-3042 as a 2-h IV infusion at 5 dose levels, from 3.25 to 8.25 mg/kg twice weekly for 3 treatments. No dose-limiting toxicities were encountered. Reduction in tumor survivin mRNA and protein were observed in 3 of 5 evaluable dogs at the 8.25 mg/kg dose cohort.ConclusionsIn conclusion, reduced survivin expression was demonstrated in lymphoma tissues in the majority of dogs treated with EZN-3042 at 8.25 mg/kg twice weekly, which was associated with minimal adverse effects. This dose may be used in future studies of EZN-3042/chemotherapy combinations in dogs with spontaneous lymphoma and other cancers.

Systemic administration with tetrahydrocannabinol causes retinal damage in BALB/c mice.

Recent years have seen substantial shifts in cultural attitudes towards cannabis for medical and recreational use. However, legalizing recreational marijuana may have adverse effects on individual and public health. As the most widely used illicit agent, cannabis is commonly reported to disrupt learning and memory. Unfortunately, the molecular mechanisms underlying behavioral impairment by cannabis abuse remain poorly understood. Tetrahydrocannabinol (THC), a major component in cannabis, causes short-term effects on the visual system, but little is known about persisting visual disturbances. This study was to investigate the effects of systemic administration with THC on retina and explore its underlying mechanisms. BALB/c mice were treated with 1 or 2 mg/kg THC intraperitoneally daily for 2 months, mice treated with vehicle as negative control. The retinal function was tested by electroretinography after THC treatment. Morphology and pathology changes of retina were detected by hematoxylin and eosin staining. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay was used to detect the apoptosis in photoreceptor cells. Enzyme-linked immunosorbent assay was used to show the inflammatory responses and oxidative stress. mRNA and protein changes were measured by real-time polymerase chain reaction and Western blot to explore the underlying mechanisms. Results indicated that 2-month treatment with THC caused retinal damage, evidenced by its functional loss and increased apoptosis in photoreceptor cells through inducing inflammatory responses and oxidative stress. Our study demonstrated that systemic administration with THC caused toxic effects on retinas of BALB/c mice, suggesting the potential mechanisms for the retina damage caused by cannabis abuse.

Moderate to high ethanol and acetaldehyde administration decreases c-fos protein expression in the hippocampus of Aldh2-knockout and C57BL/6N mice

Background: Ethanol (EtOH) and acetaldehyde (AcH) have long been associated with many adverse effects in the central nervous system. c-fos has been used as an indirect index of neural activity.
 Method: Here, we investigated the effects of systemic administration of EtOH and AcH on the expression of c-fos protein in the hippocampus of Aldh2-knockout (Aldh2-KO) mice. The animals received an intraperitoneal injection of saline (control), EtOH (1.0, 2.0 and 4.0 g/kg) or AcH (50, 100 and 200 mg/kg), and the expression of c-fos protein was measured by Western blotting.
 Result: We found that EtOH at doses of 2.0 and 4.0 g/kg decreased c-fos in wild-type (WT) mice, whereas EtOH at all three doses tested (1.0-4.0 g/kg) decreased c-fos in Aldh 2-KO mice. Likewise, AcH at doses of 100 and 200 mg/kg had a significant effect in lowering c-fos protein in both WT and Aldh2-KO mice.
 Conclusion: Our observations suggest that moderate to high EtOH and AcH can decrease the expression of c-fos protein in the mouse hippocampus. This effect may support, at least in part, the link between c-fos and spatial memory deficits following EtOH and AcH exposure as we have observed in our previous study.
 Bangladesh Journal of Medical Science Vol.19(1) 2020 p.83-89

Effect of systemic administration of phytosterol on lacrimal quality of dogs

The tear lipid layer (oily outer layer) reduces evaporation and prevents tear overflow. In dogs, reductions in the lipid components of this layer (cholesterol, triglycerides and phospholipids) can cause eye serious diseases. In this way, the tear crystallization test analyzes the lacrimal quality, however, it is less used in veterinary. As phytosterol reduces blood cholesterol, the objective of this study was to investigate, through the tear crystallization test, whether the systemic administration of this drug influences the lacrimal quality of healthy dogs and, in addition, to verify differences in the interpretation of the ophthalmic test between different evaluators. Eight beagles, healthy, of both sexes, young and adults, without clinical ophthalmic signs apparent were selected. Basal lacrimal samples (D0) were collected from the right and left eye of all animals with glass capillary tube and arranged on a glass slide for scanning the images and subsequent microscopic analysis. Subsequently, all were medicated with the phytosterol (Collestra® 650 mg: 1 capsule, orally, every 12 hours, for 15 days). After seven (D7) and fifteen (D15) days of this systemic administration, the tear crystallization test in both eyes of all dogs was again performed for statistical comparison with the baseline results. The photographs of the slides were classified by four evaluators (AV1 and AV2 with professional experience in ophthalmology and AV3 and AV4 without previous professional experience in ophthalmology), following standards established by Rolando (1984). The results were statistically verified by analysis of simple variance (ANOVA One-Way). There was no statistical difference in the tear crystallization test between the established periods and in relation to the different ophthalmic test evaluators (p≤0.05). Although phytosterols reduce blood cholesterol levels, it was observed in the present study that these drugs when administered systemically did not interfere in the tear lipid layer and, consequently, in the lacrimal quality of healthy dogs, and may be prescribed as lipid-lowering agents for patients with ocular diseases, especially the lacrimal ones.

Effect of gbpapentin on the expression of Nrf2 in dorsal root ganglion neurons of diabetic neuropathic pain rats

Objective To investigate the effect of systemic administration of gabapentin on the expression of Nrf2 in dorsal root ganglion neurons in a rat model of diabetic neuropathic pain (DNP). Methods 60 male SD rats weighing 200-220 g were randomly divided into 4 groups (n=15 each): control group (group C), DNP group, saline group (SC+ DNP group) and gabapentin group (GBP+ DNP group). Diabetes was induced with streptozocin (70 mg/kg) subcutaneously. Paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured at 1d before and 3, 7, 10, 14, 21, and 28 d after streptozocin injection, and 21 and 28 d after administration of gabapentin (50 mg·kg-1·d-1, once) intraperitoneally. Saline and gabapentin (50 mg·kg-1·d-1) were given intraperitoneally once a day for 7 d starting from 15 d after streptozocin injection in saline and gabapentin groups respectively. The expression of Nrf2 was determined at 21 d after streptozocin injection by immune-histochemistry and Western blot. Results Compared with group C, PWMT(3.95±0.57) was significantly decreased, PWTL(6.3±0.81) was significantly shorten, Nrf2 in expression was significantly decreased in DNP, SC+ DNP and group (P 0.05). Conclusion Systemic administration of gabapentin attenuates diabetic neuropathic pain by enhancing the expression of Nrf2 in DRG neurons. (Chin J Endocrinol Metab, 2018, 34: 951-954) Key words: Gabapentin; Diabetic neuropathic pain; Dorsal root ganglion; Nrf2

Effect of systemic administration of glucocorticoid on bone mineral density in the jaw bone of minipigs

Effect of systemic administration of glucocorticoid on bone mineral density in the jaw bone of minipigs

New Xymedon Analogues for Stimulation of Posttraumatic Regeneration of the Spinal Cord in Rats

Effect of systemic administration of synthetic pyrimidine derivatives, xymedon and compounds 29D and 34D, was studied in rats with experimental dosed contusion spinal cord injury. Xymedon promoted recovery of motor function after injury. Compounds 29D and 34D more effectively restored the parameters of open-field and Rotarod tests in comparison with xymedon. Compound 29D more effectively than xymedon maintained the number of Olig2+ oligodendrocytes in the corticospinal tract and NG2 cells in all investigated areas of the white matter. In the group treated with compound 34D, the differences in the number of NG2+ cells were revealed only in the anterior funiculi, where the number of these glial cells was 2-fold higher than in the xymedon-treated group. Obtained results suggest that the studied xymedon analogs, compounds 29D and 34D, can exert their therapeutic action through different molecular and cellular pathways.

Abstract 563: Combined treatment with PD-L1 blockade and a TLR7/8 agonist dramatically enhances antitumor immunity

Abstract [Aim] Toll like receptor (TLRs) are expressed in many types of immune cells and function as a key sensor of microbial products. Ligand binding to TLRs leads to activation of signaling pathways in innate immune cells, particularly dendritic cells and subsequent induction of adaptive immune responses. TLR7/8 agonists have been shown to enhance antiviral and antitumor immune responses via multiple cytokine production such as IFN-α, IL-1β, IL-6 and TNFα. Resiquimod (R-848) is a synthetic imidazoquinoline-like molecule that binds to TLR7 and TLR8. Presently, resiquimod has been used as a topical drug for skin cancer and viral infection, because of severe side effects of systemic administration. Thus far, the clinical results of anti-PD-1 or anti-PD-L1 therapy have showed great benefits by inducing tumor regression and improving survival. However, the patients obtained the benefits of this treatment are around one third. An additional approach is required to enhance the efficacy of PD-1 blockade therapy. In this study, we examined the effects of combined treatment with anti-PD-L1 antibody and a low dose of resiquimod administration in two murine tumor models (a squamous cell carcinoma cell line, SCCVII and a colon carcinoma cell line, Colon26). [Methods] Anti-PD-L1 mAb (MIH5, 200 μg/mouse) and/or resiquimod (1.73 μg/mouse) were intraperitonealy administrated at three times a week and tumor growth was evaluated. [Results and Discussion] In a Colon26 model, either anti-PD-L1 (MIH5) mAb or resiquimod treatment alone slightly decreased tumor growth, but the combined treatment dramatically reduced the tumor growth and completely eradicated the tumor in some of mice. In a SCCVII model, monotherapy with resiquimod markedly reduced the tumor growth and completely eradicated the tumor in some of mice. The combined treatment further enhanced the efficacy. The delayed combined treatment at day 7 also showed the reduction of tumor size. Functional analyses at 3-4 wks after the tumor inoculation revealed that monotherapy with resiquimod in the SCCVII model and the combined treatment in both models significantly enhanced the percentages of IFN-γ+-expressing CD8+ T cells, but did not clearly affect the percentages of Foxp3+ regulatory T cells. Our results suggest that TLR7/8 agonist administration alone markedly enhanced antitumor responses in a selected tumor model and the combined treatment with PD-L1 blockade and a TLR7/8 agonist further amplify their effects. Citation Format: Naoto Nishii, Yuta Kondo, Lixin Li, Walter Lau, Hiroyuki Harada, Miyuki Azuma. Combined treatment with PD-L1 blockade and a TLR7/8 agonist dramatically enhances antitumor immunity. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 563.

The effects of systemic administration and local microinjection into the central nervous system of the selective serotonin 5-HT2C receptor agonist RO-600175 on sleep and wakefulness in the rat.

The effects of RO-600175, a selective 5-HT2C receptor agonist, were studied in adult rats implanted for chronic sleep recordings. Intraperitoneal administration of RO-600175 (4 mg/kg) during the light phase of the light-dark cycle significantly increased wakefulness and reduced slow wave sleep and rapid-eye-movement sleep during the first 2 h of the recording period. Direct infusion of RO-600175 into the dorsal raphe nucleus (4 mmol/l), laterodorsal tegmental nucleus (4 mmol/l), or horizontal limb of the diagonal band of Broca (4 mmol/l) also decreased rapid-eye-movement sleep. It is proposed that the activation of γ-aminobutyric acid-ergic cells located in the dorsal raphe nucleus, laterodorsal tegmental nucleus, and horizontal limb of the diagonal band of Broca is responsible, at least in part, for the effects of RO-600175 on rapid-eye-movement sleep. It is suggested that the increased wakefulness observed after systemic injection of the 5-HT2C receptor ligand could be partly related to the increased release of acetylcholine in the frontal cortex and hippocampus. However, additional studies are required to characterize the neurotransmitter systems responsible for the increase in wakefulness.

Changes in the Functional Population Response of the Cat Primary Visual Cortex after Short-Term Injections of Propofol on the Background of Continuous Propofol Infusion

The effects of systemic administration of the anesthetic propofol on the amplitude of the optical signal recorded from the neuron population of the primary visual cortex of the cat were studied. The study included development of an anesthesia protocol allowing maintenance of the required depth of anesthesia without introducing artefacts into the experimental data. Optical access to the cerebral cortex was gained at the beginning of the experiment. The effects of propofol on the functional responses of the neuron population were evaluated in the experiments by optical mapping using intrinsic signals. The study addressed the stability of the population response of the brain during the whole experiment and after single doses of propofol. The results showed that prolonged administration of propofol at a constant rate had no effect on the amplitude of the optical signal recorded from the cortical surface. On this background, single concentrated doses induced transient suppression of signal amplitude. Practical recommendations are provided for long-lasting acute neurophysiological experiments using propofol anesthesia.

Effects of Dexamethasone as a Local Anaesthetic Adjuvant for Brachial Plexus Block

Abstract Background Brachial plexus nerve blocks (BPBs) have analgesic and opioid sparing benefits for upper extremity surgery. Single-injection techniques are limited by the pharmacological duration and therapeutic index of local anaesthetics (LAs). Continuous catheter techniques, while effective can present management challenges. Off-label use of perineural dexamethasone as an LA adjuvant has been utilized to prolong single-injection techniques. The objectives of this systematic review and meta-analysis are to assess the contemporary literature and quantify the effects of dexamethasone on BPB. Methods The authors searched for randomized, placebo-controlled trials that compared BPB performed with LA alone with that performed with LA and perineural dexamethasone. Meta-analysis was performed using a random effects model with subgroup analysis stratified by LA (long vs intermediate). The primary outcome was duration of sensory block or analgesia; the secondary outcomes were motor block duration, opioid consumption, and BPB complications. Results Nine trials (801 patients) were included with 393 patients receiving dexamethasone (4–10 mg). Dexamethasone prolonged the analgesic duration for long-acting LA from 730 to 1306 min [mean difference 576 min, 95% confidence interval (CI) 522–631] and for intermediate from 168 to 343 min (mean 175, 95% CI 73–277). Motor block was prolonged from 664 to 1102 min (mean 438, 95% CI 89–787). The most recent trial demonstrated equivalent prolongation with perineural or systemic administration of dexamethasone compared with placebo. Conclusions Perineural administration of dexamethasone with LA prolongs BPB effects with no observed adverse events. The effects of systemic administration of dexamethasone on BPB must be investigated.

The effect of systemic administration of gabapentin on the expression of toll-like receptor 4 in dorsal root ganglion neurons in diabetic neuropathic pain rats

Objective To investigate the effect of systemic administration of gabapentin(GBP) on the expression of toll-like receptor 4(TLR4) in dorsal root ganglion neurons in a rat model of diabetic neuropathic pain (DNP).Methods One hundred and eight male SD rats weighing 200 g-220 g were randomly divided into 4 groups (n=27):control group (group C),DNP group,saline group (SC+DNP group)and gabapentin group(GBP+DNP group).Diabetes was induced with streptozocin(70 mg/kg) subcutaneously.Paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured at 1 d before and 3,7,10,14,21,28 d after streptozocin injection and 21,28 d after administration of GBP (50 mg/kg,once)intraperitoneally.Saline and GBP (50 mg/kg) were given intraperitoneally once a day for 7 days starting from 15 d after streptozocin injection in saline and GBP groups respectively.The expression of TLR4 was determined at 21 d after streptozocin injection by immune.Histochemistry and Western blot.Results Compared with group C,PWMT (3.9 ±0.9) was significantly decreased,PWTL [(6.1 ±0.8) s]was significantly shorten,TLR4 in expression was significantly increased in DNP,SC+DNP group and GBP+DNP group (P＜0.05).Compared with SC+DNP group,PWMT(8.3±0.8)was significantly increased,PWTL[(9.9±1.2) s]was significantly prolonged,TLR4 expression was significantly decreased in GBP+DNP group (P＜0.05).There was no significant difference in the parameters mentioned above between DNP and SC+DNP group (P＞0.05).Conclusions Systemic administration of GBP attenuates diabetic neuropathic pain by inhibiting the expression of TLR4 in DRG neurons. Key words: Gabapentin; Diabetic neuropathic pain; Dorsal root ganglia; Toll-like receptor 4

The effect of systemic administration of desmopressin on cochlear function in guinea pigs

Conclusions: Systemic desmopressin (dDAVP) administration in guinea pigs for up to 2 weeks induced only minor or no significant changes in cochlear sensitivity, suggesting that other factors may be required to induce the cochlear dysfunction that is usually associated with endolymphatic hydrops. Objectives: To investigate the effects of chronic systemic administration of dDAVP, a synthetic analog of vasopressin, on cochlear sensitivity in guinea pigs. Methods: dDAVP was administered subcutaneously via a mini-osmotic pump, at a rate of 0.2 ng/kg/min (low-dose group) or 2.0 ng/kg/min (high-dose group) for up to 2 weeks. Cochlear responses (compound action potentials) and distortion product otoacoustic emissions (DPOAEs) were measured. Example specimens were scanned using X-ray micro-tomography (micro-CT). Results: Compared with the control group, the low-dose dDAVP group showed a significant threshold increase in response to a 2 kHz tone-burst after 2 weeks of treatment, and also a decrease in the amplitude of the DPOAE after 1 week of treatment. However, individual results were variable and the high-dose dDAVP group showed no significant change compared to the control group. In the micro-CT images, two of four ears in the low-dose group showed mild hydrops, but no hydrops was found in the three ears sampled from the high-dose group.

Regulation of blood glucose by administration of allogenic bone marrow derived mesenchymal stem cells into diabetic rats through modulating regeneration of both α and β islet cells

Abstract Background: Transplanting bone marrow derived mesenchymal stem cells(MSCs) have positive effects in treating many disease conditions including diabetes. To investigate the effects of systemic administration of

Effects of systemic administration or intrabursal injection of serotonin on puberty, first ovulation and follicular development in rats

To elucidate the role of serotonin in the onset of puberty, the effects of both systemic and in-ovarian bursa administration of serotonin on the neuroendocrine mechanism that modulates the onset of puberty, follicular development and first ovulation were evaluated. Two experiments were carried out. For the first, 25 or 37.5 mg kg⁻¹ of bodyweight of serotonin creatinine sulfate was administered by a subcutaneous route to 30-day-old female rats. In the second experiment, serotonin creatinine sulfate was administered directly into the ovarian bursa of 34-day-old female rats. Systemic administration of 25 or 37.5 mg kg⁻¹ of serotonin creatinine sulfate induced a delay in the ages of vaginal opening and first vaginal oestrus, a decrease in the number of ovulating animals, and serum concentrations of FSH, LH, oestradiol and progesterone. An increase in the number of Class 3 (>500 μm) and atretic follicles was observed in the ovaries of these animals. The administration of serotonin creatinine sulfate in the ovarian bursa did not modify the onset of puberty and ovulation, but a reduced serum concentration of oestradiol was observed. Our results suggest that serotonin acts on the components of the hypothalamus-hypophysis-ovary axis by modulating follicular development, ovarian functions and the onset of puberty.

Effect of mangiferin, a naturally occurring glucoxylxanthone, on fear memory in rats

Mangiferin (1,3,6,7-tetrahydroxy-2-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] -xanthen-9-one, CAS 4773-96-0), a naturally occurring glucosylxanthone, is widely distributed in higher plants and a constituent of folk medicine. In the present study the effect of systemic administration of mangiferin on behavioural outcomes of neurological function in normal rats was investigated. A single intraperitoneal injection of mangiferin (10, 50 and 100 mg/kg body weight) immediately post-training produced an impairment of long-term memory for aversive training and a reduced freezing in a dose independent manner, when given immediately post-training. The administration of mangiferin 6 h post-training did not affect fear memory. The results indicate that mangiferin might induce deficits of emotionally motivated memory.

Protective Effect of Systemic Administration of Erythropoietin on Auditory Brain Stem Response and Compound Action Potential Thresholds in an Animal Model of Cochlear Implantation

An animal model of cochlear implantation has been developed, and the hearing threshold was evaluated after different surgical procedures. The effect of perioperative systemic administration of erythropoietin on the hearing loss induced by cochlear implantation was tested. Twenty-nine guinea pigs with normal hearing underwent implantation of a 254-microm-diameter array through a cochleostomy. The effects on hearing of cochleostomy and transient and long-term array implantation (21 days) were assessed by testing of the auditory brain stem responses and compound action potentials. Eleven implanted animals received intraperitoneal administration of erythropoietin. Selected computed tomographic scans and cochlear histologic studies were performed 1 month after implantation to confirm proper placement of the array. The erythropoietin concentration at the time of surgery was assessed in samples of perilymph, cerebrospinal fluid, and blood. The cochleostomy and transient array insertion had no effect on hearing thresholds. Long-term array implantation induced a stable decrease of hearing threshold (30 dB), a decrease that was reduced by 12 dB in erythropoietin-treated animals. The erythropoietin-treated animals had better hearing preservation at higher frequencies. Fibrosis surrounding the array was seen in both groups. The hearing loss observed was probably due to the presence of the array in the cochlea. The intraperitoneal injection of erythropoietin improved the hearing threshold shift induced by implantation.