Effect of cerebrolysin on bladder function after spinal cord injury in female Wistar rats.

OBJECTIVES: To study the effect of cerebrolysin on bladder function after spinal cord injury using functional measurements in rats. METHODS: A total of 60 female rats were enrolled in this study. After induction of complete transection at T9-T10 spinal vertebrae, cerebrolysin was injected intraperitoneally, and daily in three dosages until 7 days (1 week) and continued until 28 days (4 weeks) in three groups to show the impact of that on the bladder function. Urodynamic parameters were measured in the different groups. RESULTS: Cerebrolysin injection in a dose of 1 mL/kg for 1 week showed a slight improvement in urodynamic parameters. However, infusion of 2.5 and 5 mL/kg cerebrolysin for 1 week caused an elevation in contractions and a decrease in compliance. In long-term 2.5 mL/kg cerebrolysin injection, an improvement in compliance was observed, despite relative contractions. Furthermore, the bladder pressure pattern in the 2.5 mL/kg infused rats for 4 weeks was similar to the control group, but in the group receiving 5 mL/kg cerebrolysin for 4 weeks, reduced bladder contractions and function were observed. CONCLUSIONS: Our findings suggest that cerebrolysin might be able to inhibit the emergence of neurogenic detrusor overactivity in spinal cord injured female rats.

Cerebrolysin attenuates hyperalgesia, photophobia, and neuroinflammation in a nitroglycerin-induced migraine model in rats.

Chronic migraine dramatically affects the quality of life in the migraineurs. This study examined the effect of chronic cerebrolysin (CBL) treatment on the migraine-associated symptoms in a rat model of migraine. Experiments were carried out on 8 weeks, male Wistar rats. Chronic migraine was modeled by injection (10 mg/kg, i.p) of nitroglycerin (NTG) on days 3, 5, 7, and 9. CBL (2.5 and 5 ml/kg, i.p.) was injected every day for 10 days. Mechanical and thermal withdrawal thresholds of the hind paw were examined by von Frey hairs and hot plate, respectively. Head grooming behavior was evaluated one hour following injection of NTG. Light-aversive behaviors were determined in the modified elevated plus-maze (EPM) on even days and in the light/dark box on odd days. After behavioral experiments, blood concentrations of calcitonin gene-related peptide (CGRP), pituitary adenylate cyclase-activating polypeptide (PACAP), tumor necrosis factor-a (TNF-α), and interleukin-1ß (IL-1ß) were assessed by rat specific enzyme-linked immunosorbent assay (ELISA) kits. Our results indicated that NTG significantly increased migraine-related behavioral and molecular symptoms in the animals, whereas CBL treatment markedly reduced mechanical and thermal hyperalgesia, head grooming, and light-aversive behaviors induced by NTG. Also, blood levels of CGRP, PACAP, and pro-inflammatory cytokines (TNF-α and IL-1ß) significantly decreased by CBL administration. Chronic CBL treatment showed antinociceptive and light-aversive reducing effects in the NTG-induced animal model of chronic migraine and may represent a valuable therapy for those suffering from migraine.

Permissive role of cytosolic pH acidification in neurodegeneration: A closer look at its causes and consequences.

The maintenance of cytosolic pH in its physiological range is required for normal neuronal activity, and even minor alterations can have serious consequences. This Review summarizes the current understanding of the conditions that are associated with cytosolic pH disruption and that lead to abnormal cytosolic acidification. Oxidative stress results in cytosolic acidification, and this plays a crucial role in the emergence of apoptosis in protein misfolding and excitotoxicity, ultimately leading to irreversible neuronal damage. Through the identification of mechanisms by which intraneuronal pH acidification promotes neurodegeneration, we may identify new approaches for preventing and treating neurodegenerative disorders. © 2016 Wiley Periodicals, Inc.

Effect of adenosine A2A receptor antagonists on motor disorders induced by 6-hydroxydopamine in rat.

PURPOSE: To investigate the role of adenosine A2A receptors on 6-OHDA-induced motor disorder in rat. METHODS: In order to induce experimental model of Parkinson's disease, 6-hydoxydopamine (8 µg/rat) was injected unilaterally into the SNc. After three weeks as a recovery period, 6-OHDA-induced bradykinesia and balance disturbances were assessed by using beam traversal test 10, 30 and 60 minutes after intraperitoneal injections of the drugs (caffeine, SCH58261). RESULTS: The results showed that 6-OHDA (8 µg/rat, Intra-SNc) induced motor disorders of Parkinson's disease and increased elapsed time in the beam test (p<0.001). Injection of caffeine (30 mg/kg, i.p.) and SCH58261 (2 mg/kg, i.p.) attenuated elapsed time on beam (p<0.01 and p<0.001). We showed that acute administration of caffeine and SCH 58261 can improve the 6-OHDA-induced bradykinesia and motor disturbance. CONCLUSION: Adenosine A2AR antagonists improve 6-OHDA-motor deficit and this effect seems to be mediated by the inhibition of A2A presynaptic receptors in substantia nigra pars compacta.

Effect of adenosine A2A receptor antagonists on motor disorders induced by 6-hydroxydopamine in rat

PURPOSE: To investigate the role of adenosine A2A receptors on 6-OHDA-induced motor disorder in rat. METHODS: In order to induce experimental model of Parkinson's disease, 6-hydoxydopamine (8 μg/rat) was injected unilaterally into the SNc. After three weeks as a recovery period, 6-OHDA-induced bradykinesia and balance disturbances were assessed by using beam traversal test 10, 30 and 60 minutes after intraperitoneal injections of the drugs (caffeine, SCH58261). RESULTS: The results showed that 6-OHDA (8 μg/rat, Intra-SNc) induced motor disorders of Parkinson's disease and increased elapsed time in the beam test (p<0.001). Injection of caffeine (30 mg/kg, i.p.) and SCH58261 (2 mg/kg, i.p.) attenuated elapsed time on beam (p<0.01 and p<0.001). We showed that acute administration of caffeine and SCH 58261 can improve the 6-OHDA-induced bradykinesia and motor disturbance. CONCLUSION: Adenosine A2AR antagonists improve 6-OHDA-motor deficit and this effect seems to be mediated by the inhibition of A2A presynaptic receptors in substantia nigra pars compacta.

Dampening of Serotonergic System through 5HT1A Receptors is a Promising Target for Treatment of Levodopa Induced Motor Problems.

During long-term treatment with Levodopa, majority of patients with Parkinson's disease experience some abnormal motor problems including of Levodopa induced dyskinesia (LID) and wearing off. Incredible evidences suggest that serotonergic neurons compensate some functions of lost dopaminergic neurons in Parkinson's disease especially in advanced disease stages. Therefore, it has been postulated that serotonergic neurons are the major source for development of these unwanted effects. 5HT1A receptors are located on the serotonergic neurons and are involved in regulation of normal motor functions. With respect to the role of serotonergic projection in Parkinson's disease and importance of 5HT1A receptors in motor activity it seems that inactivation of these neurons by stimulation of 5HT1A receptors could provide benefits in treatment of Levodopa induced motor impairments.

Effect of glucosamine HCl on dissolution and solid state behaviours of piroxicam upon milling.

Piroxicam is a non-steroidal anti-inflammatory drug that is characterised by low solubility and high permeability. In order to improve the drug dissolution rate, the co-grinding method was used as an approach to prepare piroxicam co-ground in the carriers such as glucosamine hydrochloride. As, this amino sugar (glucosamine HCl) has been shown to decrease pain and improve mobility in osteoarthritis in joints, therefore, the incorporation of glucosamine in piroxicam formulations would be expected to offer additional benefits to patients. The effect of the order of grinding on the dissolution of piroxicam was also investigated. Co-ground drug and glucosamine were prepared in different ratios using a ball mill. The samples were then subjected to different grinding times. In order to investigate the effect of the grinding process on the dissolution behaviour of piroxicam, the drug was ground separately in the absence of glucosamine. Mixtures of ground piroxicam and unground D-glucosamine HCl were prepared. Physical mixtures of piroxicam and glucosamine were also prepared for comparison. The properties of prepared co-ground systems and physical mixtures were studied using a dissolution tester, FTIR, SEM, XRPD and DSC. These results showed that the presence of glucosamine HCl can increase dissolution rate of piroxicam compared to pure piroxicam. Generally, all dissolution profiles showed the fastest dissolution rate when ground piroxicam was mixed with unground glucosamine. This was closely followed by the co-grinding of piroxicam with glucosamine where lower grinding times showed the fastest dissolution. The solid state studies showed that the grinding of piroxicam for longer times had no effect on polymorphic form of piroxicam, whereas mixtures of piroxicam-glucosamine ground for longer times (60 min) converted piroxicam polymorph II to polymorph I.

Buspirone improves the anti-cataleptic effect of levodopa in 6-hydroxydopamine-lesioned rats.

In Parkinson's disease (PD), prolonged exposure to L-3,4-dihydroxyphenylalanine (L-DOPA) results in motor fluctuations, such as the on-off phenomenon, and L-DOPA-induced dyskinesia. Previously, we found that activation of 5-HT(1A) in the substantia nigra pars compacta (SNc) decreased catalepsy in parkinsonian rats. In the current investigation, we attempted to evaluate the effect of buspirone on the anti-cataleptic effect of L-DOPA in 6-hydroxydopamine (6-OHDA)-lesioned male Wistar rats. Catalepsy was induced by the unilateral infusion of 6-OHDA (8 µg/2 µl/rat) into the central region of the SNc. After a 3-week recovery period, rats received L-DOPA intraperitoneally (ip; 15 mg/kg) twice daily for 20 days, and the anti-cataleptic effect of L-DOPA was assessed by the bar test at days 5, 10, 15 and 20. The results showed that L-DOPA had an anti-cataleptic effect only until day 15, and its effect was abolished on day 20. On day 21, these rats were co-treated with three different doses of buspirone (0.1, 0.5 and 2.5 mg/kg, ip) and L-DOPA (15 mg/kg, ip). At a dose of 0.5 mg/kg, buspirone improved the anti-cataleptic effect of L-DOPA. Furthermore, the effect of buspirone (0.5 mg/kg, ip) on the anti-cataleptic effect of L-DOPA (15 mg/kg, ip) was reversed by 1-(2-methoxyphenyl)-4-(4-phthalimidobutyl)piperazine hydrobromide (NAN-190; 0.5 mg/kg, ip), a 5-HT(1A) receptor antagonist. From these results, it may be concluded that buspirone improves the anti-cataleptic effect of L-DOPA in a 6-OHDA-induced animal model of PD through the activation of 5-HT(1A) receptors. In this regard, further investigations should be undertaken to clarify the exact mechanism of the interaction between 5-HT(1A) and dopaminergic neurons.