Side Of Rats Research Articles

Macroanatomical investigation of sciatic nerve in rat and quail as a model for experimental medical studies: A comparative study of anatomy

Objective: Sciatic nerve studies are still up-to-date from past to present. In recent years, rats and animals other than rats have been used for drugs to be developed to treat the sciatic nerve. This study aims to reveal the comparative anatomy of human, rat and quail and shed light on the experimental studies planned to be done. Material and Methods: 25 rats (Wistar Albino) and Japanese quail (Coturnix japonica) in 10% formalin fixation were dissected for the sciatic nerve. In addition, to show the course of the sciatic nerve in humans, the sciatic nerve was dissected in a male cadaver. Results: In rat, the nerve length between the right and left sides is more significant than the nerve thickness between the right and left sides (p=0.025). A significant difference was found in the correlation graph between the sciatic nerve thickness on the right side and the sciatic nerve thickness on the left side in rats (p=0.006) and quails (p=0.008). Conclusion: Comparative anatomy studies are very valuable for the literature. In particular, the study of a topic such as the sciatic nerve, which is on the agenda, in various experimental animals brings the importance of examining these animals morphometrically. Anatomy of the experimental animals to be studied should also be well known in order to achieve the optimal correct data in the results of correct operation and drug administration.

Increased amount of blood vessels after blue-light-emitting diode exposure during Orthodontic tooth movement in rats

Orthodontic tooth movement (OTM) results from a biological response that facilitates tooth movement. Light-emitting diode (LED) can produce a variety of beneficial biological effects. Angiogenesis plays an important role in bone remodeling; hence, the amount of blood vessels can be used as a benchmark in OTM. The objective of this study is to analyze the effects of blue LED on the amount of blood vessels visible on the tension and pressure side during OTM. This study included 48 Wistar rats that were divided into 4 groups: control group; the treatment group exposed to blue LED light for 25 seconds (T1); the treatment group exposed to blue LED light for 30 seconds (T2); and the treatment group exposed to blue LED light for 35 seconds (T3) (n = 12). An open coil spring placed on the mandibular incisors generated the orthodontic force. The amount of blood vessels present on the pressure and tension sides of the periodontal tissue was observed on histological specimens with hematoxylin–eosin staining on days 0, 3, 7, and 14 at 400× magnification. The obtained data were analyzed using two-way ANOVA followed by the post-hoc least significant different (LSD) test (P < 0.05). The amount of blood vessels on the tension and pressure sides in the T3 treatment group was higher than the other groups (P < 0.05). We conclude that exposure to blue LED increased the amount of blood vessels during OTM on the tension and pressure sides in rats.

Effect of humic acid as a photosensitizer combined with low-energy laser on orthodontic tooth movement in rats

Background/purposeHumic acid (HA) could promote light conversion reaction, and lasers accelerate orthodontic tooth movement. We investigated the effect of HA, as a photosensitizer, combined with low-energy laser on orthodontic tooth movement in rats. Materials and methodsAn orthodontic tooth movement model was established, and the upper left first molar was moved mesially by a nickel-titanium tension spring with a 50-g force. HA was injected into the rats’ abdominal cavity (80 mg/kg once daily). The periodontal tissue of the upper left upper first molar on the pressure side was irradiated (50 s once every 2 days) using a semiconductor laser (wavelength, 650 nm; power, 50 mV). Distance moved by the upper left first molar was measured at different time points, and the tissue of the first molar was sectioned and scanned by micro-computed tomography to evaluate the alveolar bone density. Tartrate-resistant acidic phosphatase staining was used to observe the osteoclast number, alveolar bone, and periodontal tissue. ResultsHA alone did not significantly affect orthodontic tooth movement, alveolar structure density, or periodontal tissue remodeling (P > 0.05). HA combined with a low-energy laser accelerated orthodontic tooth movement. The number of bone absorption lacunae and osteoclasts on the alveolar bone's pressure side increased significantly (P < 0.05), while the density decreased significantly (P < 0.05); however, no root absorption was observed. ConclusionHA can improve the conversion rate of low-energy lasers, enhance the low-energy laser effect, and promote orthodontic tooth movement and periodontal tissue reconstruction on the pressure side in rats, without causing root resorption.

EVALUATION OF ETHOSOMAL EPIGALLOCATECHIN-3-GALLATE GEL FORMULATIONS AS AN ANTIOXIDANT AND THERMOGENIC AGENT

Objective: The aim of this study was to investigate in vitro and in vivo behavior of the prepared ethosomal formulations of green tea extract, which in turn would result in enhancing their therapeutic efficacy as antioxidants and thermogenic agents in obese mice.&#x0D; Methods: Fat Wistar rats were acclimated for at least 7 d in environmentally controlled cages, then they were divided into five groups: 1st received only distilled water, 2nd received an oral dose of green tea extract, in 3rd group green tea extract loaded gel base was applied on the previously shaven dorsal side of rats and in the other 2 groups selected green tea extract loaded Ethosomal gel base were applied on the previously shaven dorsal side of rats. Total antioxidant capacity by ferric reducing ability of plasma (FRAP) method, catalase enzyme activity, malondialdehyde (MDA) and thiobarbituric acid reactive substance (TBARs) levels, and real-time qPCR of UCP2 and 3 were then determined.&#x0D; Results: Formulation of green tea extract as ethosomal preparations exhibited a controlled release rate due to the reservoir action of ethosomes. The levels of TBARs and MDA were lower in groups supplemented with green tea extracts compared to control group and in groups (3-5) received it transdermal (P&lt;0.0001 in all 3 groups) was lower than group received it orally with P = 0.0081. The messenger RNA levels of UCPs 2 and 3 in BAT were increased in those 3 groups.&#x0D; Conclusion: The results support the efficiency of ethosomal gel in penetrating the lipid rich biological membrane. The in vivo study confirms the antioxidant and thermogenic behavior of transdermal applied green tea extract.

Spontaneous Neuronal Plasticity in the Contralateral Motor Cortex and Corticospinal Tract after Focal Cortical Infarction in Hypertensive Rats

Objectives: In this study, we investigated the spontaneous neural plasticity on the contralateral side in hypertensive rats, including the expression of nerve growth factors (synaptophysin [SYN] and growth-associated protein 43 [GAP-43]), and the association between nerve fiber sprouting and redistribution, and the recovery of motor functions following sensorimotor cortical infarction. Methods: Initially, Sprague-Dawley rats were induced with renal hypertension by the bilateral renal arteries clips method. Further, they were induced with cerebral ischemia by the middle cerebral artery electrocoagulation method; 70 male rats completed the study. We compared the changes in the corticospinal tract (CST) and the expressions of SYN and GAP-43 on the contralateral side in rats with cerebral infarction using immunohistochemical staining, western blot, and biotinylated dextran amine (BDA) tracing analyses. The recovery of motor function in rats after cortical infarction was evaluated by the foot-fault and beam-walk tests. Results: The motor behavior tests revealed that the motor function of rats could recover to various degrees after focal cortical infarction. Compared with the sham-operated group, the SYN and GAP-43 levels increased in the motor cortex of the opposite hemisphere within 28 days after middle cerebral artery occlusion (MCAO). The increase in SYN and GAP-43 expressions presented differently in layers Ⅱ, Ⅲ, and Ⅴ. The amount of BDA-positive fibers also increased significantly in the denervated cervical spinal gray matter on day 56 post-MCAO. Conclusions: The increases in SYN and GAP-43 on the contralateral side of the motor cortex could promote CST sprouting and rewiring in the spinal cord gray matter and also spontaneous motor function recovery after cortical infarction.

Study on effects botulinum toxin type A injection for pathological of gastrocnemius in rats with spinal cord injury

To explore pathological characteristic of gastrocnemius (GM) and BBB motor assessment and MAS of ankle dorsiflexors in SCI model rats which were injected with BoNT-A in different time points. To make sure the proper time for BoNT-A injection. Forty-eight SD male rats (weight 260–280 g) were allocated normal control group and 12w-control group, NS-injection group and BT-injection group in this study. NS/BT-therapy groups were divided into three subgroups separately (2w-NS, 2w-BT, 4w-NS, 4w-BT, 8w-NS, 8w-BT). No injection was applied in normal control group or 12w-control group. Saline/BoNT-A was injected in right GM in NS/BT-therapy group at different time points. MAS was used to assess the ankle dorsiflexors spasticity; BBB was used to assess the movement ability of lower limb. GM at right side of rats would be forwarded for pathological examinations, such as muscle weight, myosin heavy chain electrophoretic analysis. To compare with 12W-contrl group, GM muscle weight decreased significantly in rats from BT-injection group ( P ≤ 0.05). Comparison with 12W-Contrl group, MAS and BBB values were showed no significant difference in the two injection groups ( P > 0.05). The differences in MyHC type ratio of GM between BT-injection group and Nor-Contrl group and 12W-Contrl group were statistically significant ( P ≤ 0.05); and following the injection happened in the different time points, the changes in MyHC type ratio of GM were different in each BT-injection subgroup. BoNT-A injection results in some changes in GM, such as decreased muscle weight, decreased GM/total weight. No obvious changes were happened in the ankle dorsiflexors spasticity level and the movement ability of lower limb in rats of BT/NS-injection groups. Earlier BoNT-A intervention will cause significant changes on MyHC types characterize than later intervention in GM.

Wound Repair and Regenerating Effect of Eugenol Isolated from Ethyl Acetate Soluble Fraction of Ethanolic Extract of Cinnamomum tamala Leaves in STZ Diabetic Rats

Diabetes is a chronic hyperglycaemic disorder; leads to developed several complications including delayed wound healing after any injury. These non-healing wound ends up to organ or limb salvage. The available modern medications are not capable to fully control over these complications. There are several evidences that these complications can easily treated by using herbal of folklore medicines. The leaves of Cinnamomum tamala used by traditional peoples in the treatment of diabetes and associated wound healing. In our previous study we had found that the ethanolic extract of leaves of Cinnamomum tamala is most active in treatment of wound healing in diabetic rats. The aim of our study was to find the active isolated eugenol from ethyl acetate soluble fraction of ethanolic extract of C. tamala leaves responsible for wound healing activity in diabetic rats. The Wistar albino rats were made diabetic by single i.p. injection of Streptozotocin (60 mg/kg). The excision, incision and dead space wound were created on back side of rats. The eugenol isolated from ethyl acetate soluble fraction of ethanolic extract of leaves of Cinnamomum tamala was applied topically in excision wound model while in incision and dead space wound model the eugenol isolated from ethyl acetate soluble fraction (100 mg/kg) was give orally for 16 days. In the excision wound model the wound area and day of epithelisation both were significantly decreased eugenol isolated from ethyl acetate soluble fraction treated rats. In incision wound model the significantly higher tensile strength was observed in rats treaded orally with eugenol from ethyl acetate soluble fraction.There were significant increase in weight of wet & dry granulation tissue with increased amount of hydroxyproline, collagen and elastin was observed in eugenol treated rats by ethyl acetate soluble fraction. The results suggested that the eugenol isolated from ethyl acetate soluble fraction of ethanolic extract of leaves of Cinnamomum tamala can be beneficial in treatment of wound healing in diabetic rats.

Effects of botulinum toxin type A injection for pathological characteristic of calf in rats with spinal cord injure

Objective: To explore the effect of BoTN-A on pathological characteristics of calf (GM) and motor function of ankle dorsiflexors in SCI model rats. Methods: Thirty-six SD male rats (weight 260-280 g) were randomly allocated into normal control group and 12w-control group, NS-injection group and BT-injection group in this study.NS/BT-injection groups were divided into two subgroups separately (2w-NS, 2w-BT, 8w-NS, 8w-BT). No injection was applied in normal control group or 12w-control group.Saline/BoTN-A was injected in right GM in NS/BT-injection group at two different time points(2w, 8w). GM and Sol on right side of rats would be forwarded for pathologicalexaminations, such as muscle weight, myosin heavy chain (MyHC) electrophoretic analysisat the 12th week. Results: Compared with the other three groups, the muscle weights of GM and Sol in the BT-injection group significantly decreased.MyHC type ratioof GM and Sol on the right side in the BT-injection group also significantlychanged.According to subgroup comparisons, MyHC type ratio of GM and Sol on the injectedside in the 2w-BT subgroup was significant different from that of the 8w-BT subgroup.MyHC type ratios of GM on the non-injected side in the BT injection group also changed more than normal control group.The change of MyHC type ratio of non-injected GM was significantly higher in the 2 week-BT subgroup than that in the 8-week subgroup. Conclusions: BoNT-A intervention resulted in pathological changes not only in the injected GM in SCI rats, but also in non-injected GM and non-injected Sol.The effects of earlier (2 weeks) BoTN-A intervention on pathologic characteristicsof GM and Sol were larger than that of later intervention.

Effects of acupuncture plus mild hypothermia on apoptosis-related factors in rats with cerebral ischemia-reperfusion

To investigate the effect of acupuncture plus mild hypothermia on neurological function impairment score, cerebral infarct size and apoptosis-related factors in cerebral ischemia reperfusion injury (CIRI) rats. Sixty healthy male Sprague-Dawley (SD) rats were routinely reared for 1 week. Ten rats were randomly selected as the sham operation group and 10 rats as the blank control group, while the remaining 40 rats were subjected to preparing the middle cerebral artery occlusion (MCAO) model by modified filament occlusion method. The 40 MCAO rats were further randomly divided into a model group, an acupuncture group, a mild hypothermia group and an acupuncture plus mild hypothermia group, with 10 rats in each group. Rats in the sham operation group, the blank control group and the model group did not accept treatment except binding; rats in the acupuncture group received acupuncture treatment; rats in the mild hypothermia group received mild hypothermia treatment; rats in the acupuncture plus mild hypothermia group received acupuncture and mild hypothermia treatment. 72 h after the treatment, neurological function impairment score was performed; the infarct area ratio was determined by 2,3,5-tripheyl tetrazolium chloride (TTC) staining; apoptosis of brain cells was observed by TUNEL method; the expressions of Bcl-2, Bax and Caspase-3 were detected by immunohistochemistry. Compared with the blank control group and the sham operation group, the neurological function impairment score, cerebral infarct area ratio, apoptosis, and the expressions of Bax and Caspase-3 in the model group were significantly increased, while the expression of Bcl-2 was significantly decreased, and there were significant between-group differences (all P<0.05). After the treatment, there were statistically significant differences among the treatment groups in the neurological function impairment score, cerebral infarct area ratio and apoptosis in the ischemic side of rats, as well as the expressions of Bcl-2, Bax and Caspase-3 (all P<0.05), and from the figures, tables and statistical analysis, it was found that a better tendency in the acupuncture plus mild hypothermia group than the acupuncture group or mild hypothermia group. Acupuncture plus mild hypothermia can protect the brain cells by improving neurological function impairment, decreasing cerebral infarct area ratio, reducing the number of apoptotic cells in the ischemic area and regulating the expressions of apoptosis related proteins to inhibit apoptosis.

Study based on sonoelastography technology for spastic gastrocnemius in rat with spinal cord injure

To investigate the pathological characteristic of gastrocnemius (GM) and quantitatively assess GM tissue stiffness in spinal cord injury (SCI) rat models; to explore the novel method in evaluation of GM stiffness. A total of 54 SD male rats (weight 260-280 g) were allocated into normal control group (0 w) and model groups (2, 4, 8 and 12 w) in this study. Complete SCI (T10 level) was applied in model groups. At the above different time points, Modified Ashworth Scale (MAS) was used to assess the GM spasticity; Basso, Beattie, and Bresnahan Locomotor Rating Scale (BBB) was used to assess the movement ability of lower limb. GM stiffness was assessed with shear wave sonoelastography technology in these groups. All GM at right side of rats was further checked by pathological examinations (muscle weight, ATP staining, myosin heavy chain (MyHC) electrophoretic analysis) after sonoelastography imaging examinations. After removing the overweight and underweight rat models which were alive, six rats were included in each group. There were some pathologic changes in GM in SCI rat models. Compared with normal control group, data from model groups showed ankle dorsiflexors MAS (1.5±0.8-0.8±0.7 score) was increased (P≤0.05), BBB scores of lower limb (3.2±1.0-7.2±1.3score) were decreased (P≤0.05). The GM elastic modulus was increased at dorsiflexion location in model group (25.1±2.4-37.4±5.5 kPa, P≤0.05); GM weights were decreased, ratio of type Ⅰ fibers was decreased and ratio of type Ⅱ fibers was increased in GM. Compared with normal control group, MyHC-Ⅰ was decreased, while MyHC-Ⅱ was increased according electrophoretic analysis. Both pathological characteristic and muscle stiffness of GM change after SCI. Shear-wave sonoelastography technology can be used to assess the GM stiffness in SCI rat models.

Haversian system of compact bone and comparison between endosteal and periosteal sides using three-dimensional reconstruction in rat.

The current model of compact bone is that of a system of Haversian (longitudinal) canals connected by Volkmann's (transverse) canals. Models based on either histology or microcomputed tomography do not accurately represent the morphologic detail and microstructure of this system, especially that of the canal networks and their spatial relationships. The aim of the present study was to demonstrate the morphologic pattern and network of the Haversian system and to compare endosteal and periosteal sides in rats using three-dimensional (3D) reconstruction. Ten Sprague-Dawley rats aged 8-10 weeks were used. The femurs were harvested from each rat and fixed, decalcified with 10% EDTA-2Na, serially sectioned at a thickness of 5 µm, and then stained with hematoxylin and eosin. The serial sections were reconstructed three-dimensionally using Reconstruct software. The Haversian canals in the endosteal region were found to be large, highly interconnected, irregular, and close to neighboring canals. In contrast, the canals in the periosteal region were straight and small. This combined application of 3D reconstruction and histology examinations to the Haversian system has confirmed its microstructure, showing a branched network pattern on the endosteal side but not on the periosteal side.

Activation of mammalian target of rapamycin contributes to pain nociception induced in rats by BmK I, a sodium channel-specific modulator

The mammalian target of rapamycin (mTOR) pathway is essential for maintenance of the sensitivity of certain adult sensory neurons. Here, we investigated whether the mTOR cascade is involved in scorpion envenomation-induced pain hypersensitivity in rats. The results showed that intraplantar injection of a neurotoxin from Buthus martensii Karsch, BmK I (10 μg), induced the activation of mTOR, as well as its downstream molecules p70 ribosomal S6 protein kinase (p70 S6K) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), in lumbar 5-6 dorsal root ganglia neurons on both sides in rats. The activation peaked at 2 h and recovered 1 day after injection. Compared with the control group, the ratios of p-mTOR/p-p70 S6K/p-4EBP1 in three types of neurons changed significantly. The cell typology of p-mTOR/p-p70 S6K/p-4E-BP1 immuno-reactive neurons also changed. Intrathecal administration of deforolimus, a specific inhibitor of mTOR, attenuated BmK I-induced pain responses (spontaneous flinching, paroxysmal pain-like behavior, and mechanical hypersensitivity). Together, these results imply that the mTOR signaling pathway is mobilized by and contributes to experimental scorpion sting-induced pain.

Nanofibrous nerve conduits for repair of 30-mm-long sciatic nerve defects.

It has been confirmed that nanofibrous poly(3-hydroxybutyrate-co-3-hydroxyvalerate) nerve conduit can promote peripheral nerve regeneration in rats. However, its efficiency in repair of over 30-mm-long sciatic nerve defects needs to be assessed. In this study, we used a nanofibrous poly(3-hydroxybutyrate-co-3-hydroxyvalerate) nerve conduit to bridge a 30-mm-long gap in the rat sciatic nerve. At 4 months after nerve conduit implantation, regenerated nerves were cally observed and histologically assessed. In the nanofibrous graft, the rat sciatic nerve trunk had been reconstructed by restoration of nerve continuity and formation of myelinated nerve fiber. There were Schwann cells and glial cells in the regenerated nerves. Masson's trichrome staining showed that there were no pathological changes in the size and structure of gastrocnemius muscle cells on the operated side of rats. These findings suggest that nanofibrous poly(3-hydroxybutyrate-co-3-hydroxyvalerate) nerve conduit is suitable for repair of long-segment sciatic nerve defects.

Effects of wind-dispelling drugs and deficiency-nourishing drugs of Houshiheisan compound prescription on astrocyte activation and inflammatory factor expression in the corpus striatum of cerebral ischemia rats.

This study explored protective effects of Houshiheisan and its compound prescription of wind-dispelling drugs and deficiency-nourishing drugs on cerebral ischemia in terms of astrocyte activation and inflammatory factor expression. Results suggested that Houshiheisan lessened neuronal degeneration in the corpus striatum on the ischemic side of rats following cerebral ischemia/reperfusion injury, contributed to astrocyte activation and glial fibrillary acidic protein expression in the corpus striatum and decreased the levels of interleukin-2, interleukin-6, interleukin-1β and tumor necrosis factor-α. Factor analysis results demonstrated that deficiency-nourishing drugs were more beneficial in protecting neurons and upregulating glial fibrillary acidic protein expression than wind-dispelling drugs. However, wind-dispelling drugs were more effective in increasing the number of glial fibrillary acidic protein-positive cells and reducing inflammatory factor expression than deficiency-nourishing drugs. These indicate that different ingredients of Houshiheisan suppress cerebral ischemic injury by promoting astrocyte activation and diminishing inflammatory factor expression.

Long-term effect of intraventricular injection of low-dose lipopolysaccharide on behavior, microglias and dopaminergic neurons in the substantia nigra of rats

Objective To investigate the long-term effect of inflammation on behavior,microglias and dopaminergic （DA） neurons in the substantia nigra of intracephalic inflammation rat models induced by intracerebroventricular injection of low-dose（10μg） lipopolysaccharide （LPS）. To analyze the relationship between activa- tion of microglias and DA neurons degeneration in order to explore the mechanism of inflammation in the progres- sive process of Parkinson＇s disease （PD）. Methods 50 healthy male SD rats were randomly assigned into sa- line-injected control group and 10μg LPS-injected group. All injections were made intracerebroventricularly on right side of rats with saline or LPS. Moving speed was measured at different time points. At 24 weeks and 40 weeks after saline or LPS injection, specific antibodies of OX-42 and OX-6 were used separately to detect the changes of microglia in the substantia nigra of rat. The changes in morphology and numbers of substantia nigra DA neurons were observed by tyrosine hydroxylase（TH） immunohistochemical staining. The expression and distribution of the degenerated neurons in substantia nigra were detected by using Fluoro-Jade B （FJB）. Results （1）Analysis of moving speed showed that the moving speed of 10μg LPS-injected group rats and saline-injected group rats was similar from 4 weeks to 36 weeks after injection. At 40 weeks post injection, moving speed of 10μg LPS-injected group rats decreased by 24.6% compared with that of saline-injected group rats （P〉 0.05 ）. （2）At 24 weeks and 40 weeks after injection,there were many activated 0X-42 positive microglias in the substantia nigra of 10μg LPS-in- jected group rats, but there was almost no significant activated OX-42 positive microglia in saline-injected group. OX-6 positive microglias were not found in the substantia nigra of both of two groups. （1）At 24 weeks and 40 weeks post injection, the number of TH-positive neurons in the substantia nigra of 10μg LPS-iniected rout3 rats decreasedby 24.2% （ t=4.803, P〈0.01 ） and 27.6% （ t= 3. 212, P〈0.01 ） respectively compared with those of salineinjected group. （4） There was no FJB positive neurons in the suhstantia nigra of the two group rats. Conclusion Intraventricular injection of low-dose LPS （10μg） in rats may induce long-term activation of microglias and chronic degeneration of DA neurons in the substantia nigra of rats although the necrosis are not occurs to DA neurons till 40 weeks post LPS injection. Intravenlricular injection of low-dose LPS in rats could he ideal model to study the mechanism of chronic degeneration of DA neurons in PD. Key words: Parkinson＇ s disease ; Inflammation ; Behaviour ; Microglia ; Dopaminergic neurons

Mastication overload causes an increase in O 2− production into the subnucleus oralis of the spinal trigeminal nucleus

The aim of the present study was to evaluate the production of superoxide anion (O 2 −) in the trigeminal complex nuclei after a functional mechanical overload of the teeth due to the preference for masticating on one side in rats. The preference for masticating on one side was induced by the discomfort due to a small abrasion of one molar; such lateralisation in mastication was confirmed by electromyography. The production of O 2 − was evaluated in the trigeminal nuclei by fluorescence microscopy after an injection of dihydroethidium. The results showed that there was an increased production of O 2 − in the subnucleus oralis of the spinal trigeminal nucleus in the same side where the mastication was preferred. This result demonstrates that an increased activity of non-painful sensory neurons can enhance the production of reactive oxygen species within the central second order sensory nuclei.

Exogenous corticosterone reduces l-DOPA-induced dyskinesia in the hemi-parkinsonian rat: Role for interleukin-1β

While the etiology of Parkinson's disease (PD) remains unknown, there is overwhelming evidence that neuroinflammation plays a critical role in the progressive loss of dopamine (DA) neurons. Because nearly all persons suffering from PD receive l-DOPA, it is surprising that inflammation has not been examined as a potential contributor to the abnormal involuntary movements (AIMs) that occur as a consequence of chronic l-DOPA treatment. As an initial test of this hypothesis, we examined the effects of exogenously administered corticosterone (CORT), an endogenous anti-inflammatory agent, on the expression and development of l-DOPA-induced dyskinesia (LID) in unilateral DA-depleted rats. To do this, male Sprague–Dawley rats received unilateral medial forebrain bundle 6-hydroxydopamine lesions. Three weeks later, l-DOPA primed rats received acute injections of CORT (0–3.75 mg/kg) prior to l-DOPA to assess the expression of LID. A second group of rats was used to examine the development of LID in l-DOPA naïve rats co-treated with CORT and l-DOPA for 2 weeks. AIMs and rotations were recorded. Exogenous CORT dose-dependently attenuated both the expression and development of AIMs without affecting rotations. Real-time reverse-transcription polymerase chain reaction of striatal tissue implicated a role for interleukin-1 (IL-1) β in these effects as its expression was increased on the lesioned side in rats treated with l-DOPA (within the DA-depleted striatum) and attenuated with CORT. In the final experiment, interleukin-1 receptor antagonist (IL-1ra) was microinjected into the striatum of l-DOPA-primed rats to assess the impact of IL-1 signaling on LID. Intrastriatal IL-1ra reduced the expression of LID without affecting rotations. These findings indicate a novel role for neuroinflammation in the expression of LID, and may implicate the use of anti-inflammatory agents as a potential adjunctive therapy for the treatment of LID.

Effects of streptozotocin-induced diabetes and insulin on calcium responsiveness of the rat vas deferens

In the present study, effects of streptozotocin-induced diabetes and insulin treatment on the reactivity of rat vas deferens to KCl and calmidazolium, a calmodulin antagonist, were evaluated and calmodulin levels in vas deferens tissue from diabetic and insulin-treated rats were determined. Diabetes was induced in rats by a single injection of streptozotocin. Five weeks after the induction of diabetes, one group of diabetic rats was injected with insulin for 3 weeks. After 8 weeks, vas deferens tissues on one side of diabetic and insulin-treated diabetic rats and their controls were mounted in organ bath to measure isometric tension, while the tissues on the other side of rats were homogenized to determine calmodulin levels by radioimmunoassay. Concentration–response curves to KCl were obtained in vas deferens tissues in the absence and presence of calmidazolium. The effects of KCl and calmidazolium on vas deferens isolated from 8-weeks diabetic rats were decreased. Calmodulin levels were also found to be decreased in vas deferens from diabetic rats. Decreased calmodulin levels in diabetic rat vas deferens were not corrected by insulin treatment. Only a partial correction following insulin treatment was observed in contractile effect of KCl on diabetic rat vas deferens, whereas insulin treatment increases the affinity of calmodulin in this muscle. Experimental diabetes causes an impairment in calcium/calmodulin-dependent contractile process of vas deferens, which is correctable partially following insulin therapy. The changes in the function of rat vas deferens due to streptozotocin diabetes seem to be related to impaired sexual functions in human diabetes.

Laterality of the pontocerebellar projections in the rat

This study aimed to investigate the trajectory of fibres from the pontine nuclei that reach the two sides of the cerebellum. Injections of biotinylated dextran amine (BDA) were made within the basilar pontine nuclei (BPN) and the nucleus reticularis tegmenti pontis (NRTP) in one side of rats with electrolytic injury of the middle cerebellar peduncle (MCP), ipsilateral or contralateral to the side of injection. Fibres were traced from the pontine nuclei (BPN and NRTP) to both sides of the cerebellum passing through the respective MCPs. The study carried out in rats with injury to one peduncle showed projections segregated to the half-side of the cerebellum innervated by the intact peduncle. The laterality observed was confirmed by a retrograde tracer study. In fact, injections of different fluorescent tracers in rats with injury of single MCP showed that in the pontine nuclei only cell bodies stained by the tracer injected in the half-cerebellum ipsilateral to the intact peduncle. Finally, similar injections (i.e. different fluorescent tracers in symmetric areas of the cerebellar cortex) in the cerebellum of intact brain rats showed that BPN and NRTP differ for the laterality of their projections. In fact, 82% of BPN cells project contralaterally and 18% ipsilaterally, whereas 60% of NRTP cells project contralaterally and 40% ipsilaterally. In conclusion, this study showed that the MCPs receive fibres from the pontine nuclei of both sides and project to the ipsilateral half of the cerebellum and that different contingents of projections to the two sides of the cerebellum arise from BPN and NRTP.

Effects of sibutramine on the central dopaminergic system in rodents.

The effects of sibutramine on central dopaminergic system in rats and mice were examined by neurochemical and behavioral pharmacological methods. Dopamine reuptake inhibition by sibutramine in brain synaptosomes was only 4-5 times stronger than those of amitriptyline and dosulepin, which do not exhibit dopamine uptake inhibition in vivo. Single treatment with sibutramine did not alter the brain content of dopamine and DOPAC. However, similar to methamphetamine and pargyline, sibutramine antagonized methyl-4-pheny-1,2,3,6-tetrahydro-pyridine (MPTP) induced dopamine depletion in mouse brain. In forced swimming tests of reserpinized mice, sibutramine shortened the immobilized time, similar to dopaminergic drugs including nomifensine, bupropion (dopamine-reuptake inhibitor), methamphetamine, SKF 38393 (dopamine D1 agonist), quinpirole (dopamine D2 agonist) and apomorphine (dopamine D1/D2 agonist). In addition, sibutramine caused rotational behavior toward the lesioned side in rats with unilateral lesions of the substantia nigra induced by 6-hydroxydopamine. These results suggest that sibutramine exhibits neurochemical and behavioral dopaminomimetic activity in vivo, which is mediated by dopamine reuptake inhibition by the active metabolites of sibutramine.