IRANIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
Year:2019 | Volume:3 | Issue:2 (10)|Papers Count:8

Background and aims: The retrograde neuronal death in the dorsal root ganglia (DRG) can be the main factor in poor regeneration of injured peripheral nerves occurring by increased activity of oxidant agents. The present study investigated the effect of thiamine treatment, as an antioxidant, on neuronal death after sciatic nerve transection. Methods: Twenty-five male Wistar rats were allocated in 5 experimental groups (n = 5). Group 1 was considered as intact. The sciatic nerve was transected in groups 2 to 5. Then rats were treated daily with physiological saline (control group), thiamine (50 and 100 mg/kg; i. p. ) and thiamine (1. 7 mg/kg locally). After four weeks, animals were sacrificed and L5DRG was removed for histological assessment. Results: Morphological analysis showed some no cell areas in L5DRG sections, which may be related to apoptotic cells in axotomized animals. L5DRG volume measurement showed no significant difference between intact and local thiamine treated group, while its volume was significantly reduced in other experimental groups (p < 0. 001). This parameter was also significantly reduced in control group compared with local thiamine treated group (p < 0. 001). Although the difference of L5DRG cell number in local thiamine treated group was not significant, its reduction was significant in control and intraperitoneal groups compared with intact group (p < 0. 01). The L5DRG cell count in local thiamine treated group was significantly higher than that in control group (p < 0. 01). Conclusion: These findings may indicate that thiamine if is administered in sufficient doses can be classified as neuroprotective agent.

Background and aims: Alzheimer's disease (AD) is a progressive brain disorder that is associated with dementia. The entorhinal cortex (EC) is one of the first brain regions affected in AD. High level of beta-amyloid (Aβ ) is seen in various brain regions, including the EC. Previous studies have shown that Aβ causes calcium dyshomeostasis. In this study, molecular changes in the CA1 region following microinjection of Aβ into the EC and the potential protective role of calcium channel blockers was investigated. Methods: Aβ (1 μ g/2 μ l) was injected into the right EC of male Wistar rats under stereotaxic surgery, and then a guide cannula was planted in the right ventricle. Isradipine and nimodipine were intraventricularly injected at 30 μ g daily for 6 days. On the seventh day, the expression of Calpain 2, Caspase 12 and 3 in hippocampal CA1 was measured by western blot technique. Pro-apoptotic changes were also assessed by Tunnel test. Results: Results indicated that Aβ injection into the EC increased the expression of Calpain 2, Caspase 12 and 3 in the CA1 region. Apoptotic cells were also increased in the CA1 region following amyloidopathy in the EC. Following the treatment of the rats with isradipine and nimodipine, the expression of Calpain 2, Caspase 12 and 3 decreased, and the number of apoptotic cells was returned to the control level. Conclusion: EC amyloidopathy may change the molecular profile associated with apoptosis in neighbor regions such as CA1 and treatment with calcium channel blockers can prevent the changes.

Background and aims: Toxoplasmosis is a globally prevalent parasitic infection caused by Toxoplasma gondii. A flu-like syndrome is seen in the acute phase of infection with no obvious symptoms in the chronic phase. In this study effect of co-trimaxazole on parasite load and inflammation in the brain of infected mice was examined. Methods: Mice were infected by intraperitoneal injection T. gondii cysts. Transcription of REP-529 (as indicator of parasite load) and TNF-α (as indicator of inflammation) were measured in the mice brain by RT-qPCR, at weeks 1-8 after injection of cysts, and after treatment with co-trimoxazole. Co-trimoxazole was administered 10 days before the weeks 4 and 8 of the infection for 10 days. Results: Severe ascites was observed during 4-14 days after injection of cysts. The REP-529 transcription level indicates that the parasite enters the brain 1 week after cyst injection and proliferated rapidly in the second and third weeks. TNF-α level increased and reached the maximum level in the second week and then decreased in the next weeks. Co-trimoxazole significantly reduced transcription of both REP-529 and TNF-α during 4 and 8 weeks of infection. Co-trimoxazole caused significant (p < 0. 01) weight gain in mice at the week 4 of infection compared to the untreated group. Conclusion We found chronic administration of co-trimoxazole to mice infected by T. gondii can inhibit parasite proliferation and inflammation in the brain and cure the disease.

Background and aims: Regeneration of nerve fibers in transected nerve injuries requires formation of growth cone and axonal sprouting, proliferation of Schwan cells, myelin synthesis and etc. Pharmacological interventions are recommended to improve and promote these processes. In the present study the effects of thiamine, dexamethasone and N-acetyl cysteine administrations on axonal sprouting are examined. Methods: After transection of right sciatic nerve of 24 male Wistar rats, the two ends of cut nerve were sutured into a piece of silicone tube. The rats were then divided into four groups (n = 6); receiving N-acetyl cysteine (150 mg/kg), dexamethasone (0. 2 mg/kg), thiamine (50 mg/kg) and normal saline (control) once daily by intraperitoneal injection. At the end of treatment period (16 weeks) animals were sacrificed and the axonal sprouts removed and histologically examined. Results: There was no significant difference in the number of nerve fibers, axonal diameter and myelin sheath thickness among experimental groups. However, axonal diameter was almost increased in thiamine treated group (p=0. 06). Moreover, a significant decrease (p < 0. 05) in nerve cross sectional area was observed in dexamethasone group. The axonal diameter and myelin sheath thickness were also significantly decreased (p < 0. 05) in dexamethasone group, compare to thiamine group. Conclusion: Our data indicate that sciatic nerve regeneration in rats is inhibited by dexamethasone, might be ameliorated by thiamine, and is not changed by N-acetyl cysteine.

Background and aims: Chronic administration of morphine leads to structural changes in the brain. Some studies have shown the antioxidant and neuroprotective effects of metformin. The aim of this study was to investigate the effect of metformin on working memory in morphine-treated rats. Methods: In this study, 40 male Wistar rats were used. Animals were divided into 5 experimental groups (8 rats in each group): 1-control (animals received saline, orally for 7 days); 2-Metformin (animals received 50 mg/kg metformin, orally for 7 days); 3-Morphine (animals received subcutaneous morphine 10 mg/kg twice a day for 7 days); 4 and 5-Morphine + metformin, animals received morphine and metformin (5 or 50 mg/kg, orally) daily for 7 days. To evaluate the working memory, Y-maze spontaneous alternation test was used. Lipid peroxidation was assessed by measuring level of Malondialdehyde (MDA) in hippocampal tissue of rats. Results: Morphine administration resulted in working memory deficits and increased MDA levels compared to the control group (p < 0. 001). Metformin alone, at the doses used, had no effect on the working memory but the dose of 50 mg/kg significantly improved working memory (p < 0. 01) and decreased MDA level (p < 0. 05) of the morphine-treated rats. Conclusion: Metformin can improve morphine-induced deficits in the working memory of rats.

Background and aims: The lateral hypothalamus (LH) is a main component of the brain’ s reward circuit. Previous studies have shown that high-frequency deep brain stimulation (DBS) of the LH prevents morphine-induced place preference in rats. In the present study we evaluated the effect of intra-LH DBS on the levels of dopamine receptors in the prefrontal cortex. Methods: Electrodes were implanted into the LH bilaterally. Rats were allocated to four different groups: morphine-DBS, saline-DBS, morphine-sham, and saline-sham. Morphine (5mg/kg. sc) and saline were given in four consecutive days immediately followed by DBS (130 Hz pulse repetition frequency, 150 μ A pulse amplitude, and 100 μ s pulse width) or sham-DBS for 30 min corresponding to the experimental group. One day after the last injection rats were sacrificed and the prefrontal cortex was dissected for assaying dopamine receptors and c-fos mRNA expression. Results: Morphine increased D1 receptor, decreased D2 receptor, and had no effect on D3, D4, and D5 receptors. DBS in morphine-treated rats prevented the elevation of D1 receptor, increased D2 and D3 receptors, decreased D5 receptor, and had no effect on D4 receptors. Morphine decreased c-fos mRNA levels in the prefrontal cortex and DBS increased it. Conclusion: DBS of LH influenced the brain’ s dopaminergic system particularly in the prefrontal cortex.

Background and aims: Epileptic seizures, during menstrual cycle, are mostly due to low level of progesterone. Furthermore, astrocytes influence brain excitability. Therefore, this study investigates the anticonvulsive effect of progesterone on convulsions, glutamate and GABA content and the involvement of the astrocytes through glutamine synthetase (GS) enzyme. Methods: Female Wistar rats (n = 120) were assigned in six experimental groups including; naï ve control, ovariectomized control, pilocarpine, progesterone treatment groups (0. 2, 2, and 20 mg/kg). Lithium-Pilocarpine model was used to induce convulsions and the behavior was evaluated during one hour after pilocarpine injection. Progesterone, with low, medium and high doses was daily administered for five days. Following five or thirty days, the brains were dissected and the hippocampal glutamate, GABA and the activity of glutamine synthetase were measured. Results: Latency to convulsions decreased (184%), only in high-dose (HD) progesterone group, while the duration of seizures decreased in low, medium and high (105, 59, and 265%) doses of progesterone. In the five-day sacrificed animals, the GC activity decreased (164%) in HD progesterone treated group. In the thirty-day groups, GABA increased (176%) due to pilocarpine and decreased following the progesterone treatment in the low, medium and high (106, 70, and 64%) doses. Conclusion: It is concluded that progesterone administration has anticonvulsive (concentration dependent) effects, and changes the glutamate and GABA content and astrocytic GS activity.

Background and aims: The aim of this study was to compare different isolation methods to obtain stem cells from adult human third molars pulp and investigation on their potential of osteogenic and adipogenic differentiation. Methods: Dental pulp was isolated by three ways: 1) direct culture of pulp pieces, 2) enzymatic digestion of pulp using collagenase and dispase, and 3) direct culture of pulp pieces and fixing it with lamella. Stem cell surface markers were analyzed by flow cytometry method. Adypogenic and osteogenic differentiation were verified by Oil Red O staining and Alizarin Red S staining, respectively. Results: The growth of cells cultured after enzymatic digestion was faster than those isolated by other methods and the use of lamella increased the risk of infection and cell damage. Conclusion: Dental pulp stem cells isolated with enzymatic digestion has faster growth and might be as an available resource both for research and tissue engineering.