Neuroprotective Effect of β-Lapachone in MPTP-Induced Parkinson's Disease Mouse Model: Involvement of Astroglial p-AMPK/Nrf2/HO-1 Signaling Pathways

Parkinson's disease is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons within the substantia nigra pars compacta. In the present study, we investigated whether β-Lapachone (β-LAP), a natural naphthoquinone compound isolated from the lapacho tree (Tabebuia avellanedae), elicits neuroprotective effects in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mouse model. β-LAP reduced the tyrosine hydroxylase (TH)-immuno-reactive fiber loss induced by MPTP in the dorsolateral striatum, and alleviated motor dysfunction as determined by the rotarod test. In addition, β-LAP protected against MPTP-induced loss of TH positive neurons, and upregulated B-cell lymphoma 2 protein (Bcl-2) expression in the substantia nigra. Based on previous reports on the neuroprotective role of nuclear factor-E2-related factor-2 (Nrf2) in neurodegenerative diseases, we investigated whether β-LAP induces upregulation of the Nrf2-hemeoxygenae-1 (HO-1) signaling pathway molecules in MPTP-injected mouse brains. Western blot and immunohistochemical analyses indicated that β-LAP increased HO-1 expression in glial fibrillary acidic protein-positive astrocytes. Moreover, β-LAP increased the nuclear translocation and DNA binding activity of Nrf2, and the phosphorylation of upstream adenosine monophosphate-activated protein kinase (AMPK). β-LAP also increased the localization of p-AMPK and Nrf2 in astrocytes. Collectively, our data suggest that β-LAP exerts neuroprotective effect in MPTP-injected mice by upregulating the p-AMPK/Nrf2/HO-1 signaling pathways in astrocytes.

Exploratory, cognitive, and depressive-like behaviors in adult and pediatric mice exposed to controlled cortical impact

OBJECTIVE: Sequelae of behavioral impairments associated with human traumatic brain injury (TBI) include neurobehavioral problems. We compared exploratory, cognitive, and depressive-like behaviors in pediatric and adult male mice exposed to controlled cortical impact (CCI).METHODS: Pediatric (21 to 25 days old) and adult (8 to 12 weeks old) male C57Bl/6 mice underwent CCI at a 2-mm depth of deflection. Hematoxylin and eosin staining was performed 3 to 7 days after recovery from CCI, and injury volume was analyzed using ImageJ. Neurobehavioral characterization after CCI was performed using the Barnes maze test (BMT), passive avoidance test, open-field test, light/dark test, tail suspension test, and rotarod test. Acutely and subacutely (3 and 7 days after CCI, respectively), CCI mice showed graded injury compared to sham mice for all analyzed deflection depths.RESULTS: Time-dependent differences in injury volume were noted between 3 and 7 days following 2-mm TBI in adult mice. In the BMT, 2-mm TBI adults showed spatial memory deficits compared to sham adults (P < 0.05). However, no difference in spatial learning and memory was found between sham and 2-mm CCI groups among pediatric mice. The open-field test, light/dark test, and tail suspension test did not reveal differences in anxiety-like behaviors in both age groups.CONCLUSION: Our findings revealed a graded injury response in both age groups. The BMT was an efficient cognitive test for assessing spatial/non-spatial learning following CCI in adult mice; however, spatial learning impairments in pediatric mice could not be assessed.

Spatial Learning and Motor Deficits in Vacuolar Protein Sorting-associated Protein 13b (Vps13b) Mutant Mouse

Vacuolar protein sorting-associated protein 13B (VPS13B), also known as COH1, is one of the VPS13 family members which is involved in transmembrane transport, Golgi integrity, and neuritogenesis. Mutations in the VPS13B gene are associated with Cohen syndrome and other cognitive disorders such as intellectual disabilities and autism spectrum disorder (ASD). However, the patho-physiology of VPS13B-associated cognitive deficits is unclear, in part, due to the lack of animal models. Here, we generated a Vps13b exon 2 deletion mutant mouse and analyzed the behavioral phenotypes. We found that Vps13b mutant mice showed reduced activity in open field test and significantly shorter latency to fall in the rotarod test, suggesting that the mutants have motor deficits. In addition, we found that Vps13b mutant mice showed deficits in spatial learning in the hidden platform version of the Morris water maze. The Vps13b mutant mice were normal in other behaviors such as anxiety-like behaviors, working memory and social behaviors. Our results suggest that Vps13b mutant mice may recapitulate key clinical symptoms in Cohen syndrome such as intellectual disability and hypotonia. Vps13b mutant mice may serve as a useful model to investigate the pathophysiology of VPS13B-associated disorders.

Analgesic effects of eucalyptus essential oil in mice / 대한통증학회지

BACKGROUND: The use of aroma oils dates back to at least 3000 B.C., where it was applied to mummify corpses and treat the wounds of soldiers. Since the 1920s, the term “aromatherapy” has been used for fragrance therapy with essential oils. The purpose of this study was to determine whether the essential oil of Eucalyptus (EOE) affects pain pathways in various pain conditions and motor coordination. METHODS: Mice were subjected to inhalation or intraperitoneal injection of EOE, and its analgesic effects were assessed by conducting formalin, thermal plantar, and acetic acid tests; the effects of EOE on motor coordination were evaluated using a rotarod test. To determine the analgesic mechanism, 5′-guanidinonaltrindole (κ-opioid antagonist, 0.3 mg/kg), naltrindole (δ-opioid antagonist, 5 mg/kg), glibenclamide (δ-opioid antagonist, 2 mg/kg), and naloxone (μ-opioid antagonist, 4, 8, 12 mg/kg) were injected intraperitoneally. RESULTS: EOE showed an analgesic effect against visceral pain caused by acetic acid (EOE, 45 mg/kg); however, no analgesic effect was observed against thermal nociceptive pain. Moreover, it was demonstrated that EOE did not have an effect on motor coordination. In addition, an anti-inflammatory effect was observed during the formalin test. CONCLUSIONS: EOE, which is associated with the μ-opioid pain pathway, showed potential effects against somatic, inflammatory, and visceral pain and could be a potential therapeutic agent for pain.

Effects of Electric Cortical Stimulation (ECS) and Transcranial Direct Current Stimulation (tDCS) on Rats With a Traumatic Brain Injury

OBJECTIVE: To evaluate the effects of electric cortical stimulation (ECS) and transcranial direct current stimulation (tDCS) on motor and cognitive function recovery and brain plasticity in focal traumatic brain injury (TBI) of rats model. METHODS: Forty rats were pre-trained to perform a single pellet reaching task (SPRT), rotarod test (RRT), and Y-maze test for 14 days, then a focal TBI was induced by a weight drop model on the motor cortex. All rats were randomly assigned to one of the three groups: anodal ECS (50 Hz and 194 μs) (ECS group), tDCS (0.1 mA, 50 Hz and 200 μs) (tDCS group), and no stimulation as a control group. Four-week stimulation, including rehabilitation, was started 3 days after the operation. SPRT, RRT, and Y-maze were measured from day 1 to day 28 after the TBI was induced. Histopathological and immunohistochemistry staining evaluations were performed at 4 weeks. RESULTS: SPRT was improved from day 7 to day 26 in ECS, and from day 8 to day 26 in tDCS compared to the control group (p < 0.05). SPRT of ECS group was significantly improved on days 3, 8, 9, and 17 compared to the tDCS group. Y-maze was improved from day 8 to day 16 in ECS, and on days 6, 12, and 16 in the tDCS group compared to the control group (p < 0.05). Y-maze of the ECS group was significantly improved on day 9 to day 15 compared to the tDCS group. The c-Fos protein expression was better in the ECS group and the tDCS group compared to the control group. CONCLUSION: Electric stimulation in rats modified with a focal TBI is effective for motor recovery and brain plasticity. ECS induced faster behavioral and cognitive improvements compared to tDCS during the recovery period of rats with a focal TBI.

Potassium Bromate-induced Changes in the Adult Mouse Cerebellum Are Ameliorated by Vanillin / 生物医学与环境科学（英文）

OBJECTIVE@#The current study aimed to elucidate the effect of vanillin on behavioral changes, oxidative stress, and histopathological changes induced by potassium bromate (KBrO3), an environmental pollutant, in the cerebellum of adult mice.@*METHODS@#The animals were divided into four groups: group 1 served as a control, group 2 received KBrO3, group 3 received KBrO3 and vanillin, and group 4 received only vanillin. We then measured behavioral changes, oxidative stress, and molecular and histological changes in the cerebellum.@*RESULTS@#We observed significant behavioral changes in KBrO3-exposed mice. When investigating redox homeostasis in the cerebellum, we found that mice treated with KBrO3 had increased lipid peroxidation and protein oxidation in the cerebellum. These effects were accompanied by decreased Na+-K+ and Mg2+ ATPase activity and antioxidant enzyme gene expression when compared to the control group. Additionally, there was a significant increase in cytokine gene expression in KBrO3-treated mice. Microscopy revealed that KBrO3 intoxication resulted in numerous degenerative changes in the cerebellum that were substantially ameliorated by vanillin supplementation. Co-administration of vanillin blocked the biochemical and molecular anomalies induced by KBrO3.@*CONCLUSION@#Our results demonstrate that vanillin is a potential therapeutic agent for oxidative stress associated with neurodegenerative diseases.

Chronic dosing with mirtazapine does not produce sedation in rats

Objective: Sedation/somnolence are major side effects of pharmacotherapies for depression, and negatively affect long-term treatment compliance in depressed patients. Use of mirtazapine (MIR), an atypical antidepressant approved for the treatment of moderate to severe depression with comorbid anxiety disorders, is associated with significant sedation/somnolence, especially in short-term therapy. Nonetheless, studies with human subjects suggest that MIR-induced sedation is transient, especially when high and repeated doses are used. The purpose of this study was to explore the effects of acute and chronic administration of different doses of MIR on sedation in the rat. Methods: Assessment of sedation was carried out behaviorally using the rotarod, spontaneous locomotor activity, and fixed-bar tests. Results: A 15-mg/kg dose of MIR induced sedative effects for up to 60 minutes, whereas 30 mg/kg or more produced sedation within minutes and only in the first few days of administration. Conclusion: These results suggest that 30 mg/kg is a safe, well-tolerated dose of MIR which generates only temporary sedative effects.

Histopathological and Neurobehavioral Characterization in Adult Mice Exposed to Traumatic Brain Injury

PURPOSE: Traumatic brain injury (TBI) is a significant cause of morbidity and mortality worldwide. Severity of the initial insult is one of the most significant factors affecting outcome following TBI. In order to investigate the mechanisms of cellular injury and develop novel therapeutic strategies for TBI, we designed a standardized animal TBI model and evaluated histological and functional outcomes according to the degree of impact severity. METHODS: Male adult C57Bl/6 mice underwent controlled cortical impact (CCI) at varying depths of deflection (1.0-2.0 mm). We performed hematoxylin and eosin staining at 7 days after recovery from TBI. Neurobehavioral characterization after TBI was analyzed by the Barnes maze test, passive avoidance test, open field test, rotarod test, tail suspension test, and light/dark test. RESULTS: We observed a graded injury response according to the degree of deflection depths tested (diameter, 3 mm; velocity, 3 m/s; and duration, 500 ms) compared to sham controls. In the Barnes maze test, the severe TBI (2 mm depth) group showed reduced spatial memory as compared with the sham and mild TBI (1 mm depth) groups at 7 days after TBI. There was a significant difference in the results of the open field test and light/dark test among the three groups. CONCLUSION: Our findings demonstrate that the graded injury responses following TBI resulted in differential histopathological and behavioral outcomes in a mouse experimental CCI model. Thus, a model of CCI with histologic/behavioral outcome analysis may offer a reliable and convenient design for preclinical TBI research involving mice.

Assessment of Blood-Brain Barrier Permeability by Dynamic Contrast-Enhanced MRI in Transient Middle Cerebral Artery Occlusion Model after Localized Brain Cooling in Rats

OBJECTIVE: The purpose of this study was to evaluate the effects of localized brain cooling on blood-brain barrier (BBB) permeability following transient middle cerebral artery occlusion (tMCAO) in rats, by using dynamic contrast-enhanced (DCE)-MRI. MATERIALS AND METHODS: Thirty rats were divided into 3 groups of 10 rats each: control group, localized cold-saline (20℃) infusion group, and localized warm-saline (37℃) infusion group. The left middle cerebral artery (MCA) was occluded for 1 hour in anesthetized rats, followed by 3 hours of reperfusion. In the localized saline infusion group, 6 mL of cold or warm saline was infused through the hollow filament for 10 minutes after MCA occlusion. DCE-MRI investigations were performed after 3 hours and 24 hours of reperfusion. Pharmacokinetic parameters of the extended Tofts-Kety model were calculated for each DCE-MRI. In addition, rotarod testing was performed before tMCAO, and on days 1-9 after tMCAO. Myeloperoxidase (MPO) immunohisto-chemistry was performed to identify infiltrating neutrophils associated with the inflammatory response in the rat brain. RESULTS: Permeability parameters showed no statistical significance between cold and warm saline infusion groups after 3-hour reperfusion 0.09 ± 0.01 min-1 vs. 0.07 ± 0.02 min-1, p = 0.661 for K(trans); 0.30 ± 0.05 min-1 vs. 0.37 ± 0.11 min-1, p = 0.394 for kep, respectively. Behavioral testing revealed no significant difference among the three groups. However, the percentage of MPO-positive cells in the cold-saline group was significantly lower than those in the control and warm-saline groups (p < 0.05). CONCLUSION: Localized brain cooling (20℃) does not confer a benefit to inhibit the increase in BBB permeability that follows transient cerebral ischemia and reperfusion in an animal model, as compared with localized warm-saline (37℃) infusion group.

Neuroprotective effect of caffeic acid phenethyl ester in 3-nitropropionic acid-induced striatal neurotoxicity

Caffeic acid phenethyl ester (CAPE), derived from honeybee hives, is a bioactive compound with strong antioxidant activity. This study was designed to test the neuroprotective effect of CAPE in 3-nitropropionic acid (3NP)-induced striatal neurotoxicity, a chemical model of Huntington's disease (HD). Initially, to test CAPE's antioxidant activity, a 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) antioxidant assay was employed, and CAPE showed a strong direct radical-scavenging eff ect. In addition, CAPE provided protection from 3NP-induced neuronal cell death in cultured striatal neurons. Based on these observations, the in vivo therapeutic potential of CAPE in 3NP-induced HD was tested. For this purpose, male C57BL/6 mice were repeatedly given 3NP to induce HD-like pathogenesis, and 30 mg/kg of CAPE or vehicle (5% dimethyl sulfoxide and 95% peanut oil) was administered daily. CAPE did not cause changes in body weight, but it reduced mortality by 29%. In addition, compared to the vehicle-treated group, robustly reduced striatal damage was observed in the CAPE-treated animals, and the 3NP-induced behavioral defi cits on the rotarod test were signifi cantly rescued after the CAPE treatment. Furthermore, immunohistochemical data showed that immunoreactivity to glial fibrillary acidic protein (GFAP) and CD45, markers for astrocyte and microglia activation, respectively, were strikingly reduced. Combined, these data unequivocally indicate that CAPE has a strong antioxidant eff ect and can be used as a potential therapeutic agent against HD.

The Effect of Donor-Dependent Administration of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells following Focal Cerebral Ischemia in Rats

Stroke is an ischemic disease caused by clotted vessel-induced cell damage. It is characterized by high morbidity and mortality and is typically treated with a tissue plasminogen activator (tPA). However, this therapy is limited by temporal constraints. Recently, several studies have focused on cell therapy as an alternative treatment. Most researches have used fixed donor cell administration, and hence, the effect of donor-dependent cell administration is unknown. In this study, we administered 3 types of donor-derived human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) in the ischemic boundary zone of the ischemic stroke rat model. We then performed functional and pathological characterization using rotarod, the limb placement test, and immunofluorescent staining. We observed a significant decrease in neuron number, and notable stroke-like motor dysfunction, as assessed by the rotarod test (~40% decrease in time) and the limb placement test (4.5 point increase) in control rats with ischemic stroke. The neurobehavioral performance of the rats with ischemic stroke that were treated with hUCB-MSCs was significantly better than that of rats in the vehicle-injected control group. Regardless of which donor cells were used, hUCB-MSC transplantation resulted in an accumulation of neuronal progenitor cells, and angiogenic and tissue repair factors in the ischemic boundary zone. The neurogenic and angiogenic profiles of the 3 types of hUCB-MSCs were very similar. Our results suggest that intraparenchymal administration of hUCB-MSCs results in significant therapeutic effects in the ischemic brain regardless of the type of donor.

Neurobehavioral Assessment of Rats Exposed to Yttrium Nitrate during Development / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>The aim of this study was to assess the effects of yttrium nitrate on neurobehavioral development in Sprague-Dawley rats.</p><p><b>METHODS</b>Dams were orally exposed to 0, 5, 15, or 45 mg/kg daily of yttrium nitrate from gestation day (GD) 6 to postnatal day (PND) 21. Body weight and food consumption were monitored weekly. Neurobehavior was assessed by developmental landmarks and reflexes, motor activity, hot plate, Rota-rod and cognitive tests. Additionally, brain weights were measured on PND 21 and 70.</p><p><b>RESULTS</b>No significant difference was noted among all groups for maternal body weight and food consumption. All yttrium-exposed offspring showed an increase in body weight on PND 21; however, no significant difference in body weight for exposed pups versus controls was observed 2 weeks or more after the yttrium solution was discontinued. The groups given 5 mg/kg daily decreased significantly in the duration of female forelime grip strength and ambulation on PND 13. There was no significant difference between yttrium-exposed offspring and controls with respect to other behavioral ontogeny parameters and postnatal behavioral test results.</p><p><b>CONCLUSION</b>Exposure of rats to yttrium nitrate in concentrations up to 45 mg/kg daily had no adverse effects on their neurobehavioral development.</p>

Effect of Epidural Electrical Stimulation and Repetitive Transcranial Magnetic Stimulation in Rats With Diffuse Traumatic Brain Injury

OBJECTIVE: To evaluate the effects of epidural electrical stimulation (EES) and repetitive transcranial magnetic stimulation (rTMS) on motor recovery and brain activity in a rat model of diffuse traumatic brain injury (TBI) compared to the control group. METHODS: Thirty rats weighing 270-285 g with diffuse TBI with 45 kg/cm2 using a weight-drop model were assigned to one of three groups: the EES group (ES) (anodal electrical stimulation at 50 Hz), the rTMS group (MS) (magnetic stimulation at 10 Hz, 3-second stimulation with 6-second intervals, 4,000 total stimulations per day), and the sham-treated control group (sham) (no stimulation). They were pre-trained to perform a single-pellet reaching task (SPRT) and a rotarod test (RRT) for 14 days. Diffuse TBI was then induced and an electrode was implanted over the dominant motor cortex. The changes in SPRT success rate, RRT performance time rate and the expression of c-Fos after two weeks of EES or rTMS were tracked. RESULTS: SPRT improved significantly from day 8 to day 12 in the ES group and from day 4 to day 14 in the MS group (p<0.05) compared to the sham group. RRT improved significantly from day 6 to day 11 in ES and from day 4 to day 9 in MS compared to the sham group. The ES and MS groups showed increased expression of c-Fos in the cerebral cortex compared to the sham group. CONCLUSION: ES or MS in a rat model of diffuse TBI can be used to enhance motor recovery and brain activity.

Enhancement of Short-Term Memory by Methyl-6-(Phenylethynyl)-Pyridine in the BTBR T+tf/J Mouse Model of Autism Spectrum Disorder

BACKGROUND: Autism spectrum disorder (ASD) encompasses a range of disorders that are characterized by social and communication deficits and repetitive behaviors. This study evaluated the effect of methyl-6-(phenylethynyl)-pyridine (MPEP), an antagonist of the mGluR5 metabotropic glutamate receptor, on memory enhancement in the BTBR T+tf/J (BTBR) mouse strain, which has been recognized as a model of ASD. METHODS: The pharmacological effects of MPEP on memory and motor coordination were assessed using the Morris water maze and rotarod tests in BTBR and C57BL/6J (B6) mice. Furthermore, we performed morphological analyses of cerebellar foliation in BTBR and B6 mice using hematoxylin and eosin staining. RESULTS: MPEP-treated BTBR mice exhibited improved learning and memory in the Morris water maze test. MPEP administration also improved motor coordination in the rotarod test. However, no significant difference was observed regarding the numbers of Purkinje cells in the cerebella of BTBR versus normal B6 mice. CONCLUSION: This study suggests that the mGluR5 antagonist MPEP has the potential to ameliorate learning and memory dysfunction and impaired motor coordination in BTBR mice. These results further suggest that the BTBR mouse model may be useful in pharmacological studies investigating drugs that could potentially alleviate cognitive dysfunction in ASD.

An interleukin-33/ST2 signaling deficiency reduces overt pain-like behaviors in mice

Interleukin (IL)-33, the most recent member of the IL family of cytokines, signals through the ST2 receptor. IL-33/ST2 signaling mediates antigen challenge-induced mechanical hyperalgesia in the joints and cutaneous tissues of immunized mice. The present study asked whether IL-33/ST2 signaling is relevant to overt pain-like behaviors in mice. Acetic acid and phenyl-p-benzoquinone induced significant writhing responses in wild-type (WT) mice; this overt nociceptive behavior was reduced in ST2-deficient mice. In an antigen-challenge model, ST2-deficient immunized mice had reduced induced flinch and licking overt pain-like behaviors. In the formalin test, ST2-deficient mice also presented reduced flinch and licking responses, compared with WT mice. Naive WT and ST2-deficient mice presented similar responses in the rota-rod, hot plate, and electronic von Frey tests, indicating no impairment of motor function or alteration in basal nociceptive responses. The results demonstrate that IL-33/ST2 signaling is important in the development of overt pain-like behaviors.

Neuroprotective Effect of Rapamycin (Autophagy Enhancer) in Transgenic SOD1-G93A Mice of Amyotrophic Lateral Sclerosis / 대한임상신경생리학회지

BACKGROUND: The autophagy is the major route for lysosomal degradation of misfolded protein aggregates and oxidative cell components. We hypothesized that rapamycin (autophagy enhancer) would prolong the survival of motor neuron and suppress the disease progression in amyotrophic lateral sclerosis (ALS). METHODS: A total of 24 transgenic mice harboring the human G93A mutated SOD1 gene were used. The clinical status involving rotarod test and survival, and biochemical study of ALS mice model were evaluated. RESULTS: The onset of symptoms was significantly delayed in the rapamycin administration group compared with the control group. However, after the clinical symptom developed, the rapamycin exacerbated the disease progression and shortened the survival of ALS mice model, and apoptosis signals were up-regulated compared with control group. CONCLUSIONS: Even though further detailed studies on the relevancy between autophagy and ALS will be needed, our results revealed that the rapamycin administration was not effective for being novel promising therapeutic strategy in ALS transgenic mice and exacerbated the apoptosis.

Anti-Allodynic Effects of Levodopa in Neuropathic Rats

PURPOSE: Levodopa is the most effective anti-Parkinsonian agent. It has also been known to exhibit analgesic properties in laboratory and clinical settings. However, studies evaluating its effects on neuropathic pain are limited. The aim of the present study was to examine the anti-allodynic effects of levodopa in neuropathic rats. MATERIALS AND METHODS: Sprague-Dawley male rats underwent the surgical procedure for L5 and L6 spinal nerves ligation. Sixty neuropathic rats were randomly divided into 6 groups for the oral administration of distilled water and levodopa at 10, 30, 50, 70, and 100 mg/kg, respectively. We co-administered carbidopa with levodopa to prevent peripheral synthesis of dopamine from levodopa, and observed tactile, cold, and heat allodynia pre-administration, and at 15, 30, 60, 90, 120, 150, 180, and 240 min after drug administration. We also measured locomotor function of neuropathic rats using rotarod test to examine whether levodopa caused side effects or not. RESULTS: Distilled water group didn't show any difference in all allodynia. For the levodopa groups (10-100 mg/kg), tactile and heat withdrawal thresholds were increased, and cold withdrawal frequency was decreased dose-dependently (p0.05). CONCLUSION: Levodopa reversed tactile, cold and heat allodynia in neuropathic rat without any side effects.

Pulsed ultrasound therapy accelerates the recovery of skeletal muscle damage induced by Bothrops jararacussu venom

We studied the effect of pulsed ultrasound therapy (UST) and antibothropic polyvalent antivenom (PAV) on the regeneration of mouse extensor digitorum longus muscle following damage by Bothrops jararacussu venom. Animals (Swiss male and female mice weighing 25.0 ± 5.0 g; 5 animals per group) received a perimuscular injection of venom (1 mg/kg) and treatment with UST was started 1 h later (1 min/day, 3 MHz, 0.3 W/cm², pulsed mode). Three and 28 days after injection, muscles were dissected and processed for light microscopy. The venom caused complete degeneration of muscle fibers. UST alone and combined with PAV (1.0 mL/kg) partially protected these fibers, whereas muscles receiving no treatment showed disorganized fascicules and fibers with reduced diameter. Treatment with UST and PAV decreased the effects of the venom on creatine kinase content and motor activity (approximately 75 and 48%, respectively). Sonication of the venom solution immediately before application decreased the in vivo and ex vivo myotoxic activities (approximately 60 and 50%, respectively). The present data show that UST counteracts some effects of B. jararacussu venom, causing structural and functional improvement of the regenerated muscle after venom injury.

Effects of bilateral electrolytic lesions of the dorsomedial striatum on motor behavior and spatial learning in rats

The dorsal striatum plays an important role in the control of motor activity and learning processes within the basal ganglia circuitry. Furthermore, recent works have suggested functional differentiation between subregions of the dorsal striatum. The present study examined the effects of bilateral electrolytic lesions of the dorsomedial striatum on motor behavior and learning ability in rats using a series of behavioral tests. 20 male wistar rats were used in the experiment and behavioral assessment were conducted using open field test, rotarod test and 8-arm radial maze. In the open field test, rats with bilateral electrolytic lesions of the dorsomedial striatum showed a normal motor function in the horizontal locomotor activity, while in rearing activity they displayed a statistically significant motor impairment when compared to sham operated group. In the rotarod test, a deficit in motor coordination and acquisition of skilled behavior was observed in rats with bilateral electrolytic lesions of the dorsomedial striatum compared to sham. However, radial maze performance revealed similar capacity in the acquisition of learning task between experimental groups. Our results support the premise of the existence of functional dissociation between the dorsomedial and the dorsolateral regions of the dorsal striatum. In addition, our data suggest that the associative dorsomedial striatum may be as critical in striatum-based motor control

Magnetic Resonance Spectroscopy Findings According to the Route of Injecting Stem Cells in Experimental Traumatic Brain Injured Rats

OBJECTIVE: To identify the effective injection route for adult human bone marrow stromal cells into traumatic brain injured rats. METHOD: The TBI rats were created by the lateral percussion model (HD1700, Dragonfly, Silver Spring, USA). Eight rats without stem cell transplantation were assigned to a control group. We performed adult human bone marrow stromal cell transplantation into the contralateral hemisphere (n=7), the ipsilateral brain lesion (n=8) and via a tail vein (n=11), respectively, at 24 hours after brain injury. For all of the groups, MRS (magnetic resonance spectroscopy) study, behavior tests, rotarod tests and Barnes maze tests were conducted on day 1, day 7, day 42 and day 84. Sixteen rats were randomly assigned and were sacrificed for immunohistochemical staining. RESULTS: At day 42 (p=0.048) and day 84 (p=0.031) after TBI, the ratio of N-acetylaspartate to creatine (NAA/Cr) of the ipsilateral hemisphere was decreased in the control group, as assessed by MRS, whereas the ratio was increased in the other groups. On the post hoc analysis, significant differences were obtained among the intravenous group and the control group for the NAA/Cr ratio of the ipsilateral hemisphere at day 84 after TBI (p=0.050). However, there was no significant improvement on the behavior test, the rotarod test and the Barnes maze test. The cells were positively stained with antibodies to MAB-1281 and to GFAP. CONCLUSION: We confirmed that adult human bone marrow stromal cell transplantation induced an increase of the NAA/Cr ratio of the ipsilateral hemisphere at day 84 in the intravenous group. Therefore, we suggest the intravenous route is more effective for mesenchymal stem cell transplantation.