Displacement of center of mass in dogs in response to foot sensory stimulation.

OBJECTIVE: Evaluate center of mass (CoM) displacement values during four-limb and three-limb standing with limb suspension in dogs before and after applying sensory stimulation to a forelimb or hindlimb. STUDY DESIGN: Experimental study. ANIMALS: Six clinically normal beagles. METHODS: A four force-plate apparatus was built to assess static weight distribution. Dogs stood on the device with one limb in contact with each force plate. We created a plastic device to induce sensory stimulation so that lameness could not be detected visually when stimulating the paw. Experimenters confirmed the degree of lameness by walking before and after measurement. Body-weight shifts were induced via suspension of each limb and transient sensory stimulation to the right forelimb or left hindlimb. CoMs of five postures were compared, with and without transient sensory stimulation. RESULTS: The four-limb CoM was located cranial to the center of the X- and Y-axis coordinates (X: -0.82 ± 9.12, Y: 61.00 ± 5.82). During three-limb standing with suspension of either forelimb, CoM shifted backward toward the contralateral side compared to four-limb standing. During hindlimb suspension, CoM shifted to the contralateral side. With right forelimb sensory stimulation, there were large CoM changes for both four-limb and three-limb standing (X: -34.53 ± 9.09, Y: 52.21 ± 6.88). CoM changes were small with left hindlimb sensory stimulation (X: 6.47 ± 13.86, Y: 69.41 ± 5.55). CONCLUSION: CoMs during four-limb and three-limb standing were influenced by sensory stimulation of a forelimb and, to a lesser extent, of a hindlimb. CLINICAL SIGNIFICANCE: Static evaluation of CoM may aid clinicians in the diagnosis and recovery of forelimb lameness.

Recurrence analysis of intraoperative acridine orange-photodynamic therapy for dogs with intranasal tumors.

Intraoperative acridine orange-photodynamic therapy (AO-PDT) and cribriform plate irradiation are used to treat canine intranasal tumors. The purpose of this study was to evaluate the effects of AO-PDT on intranasal tumors and the recurrence rate of tumors after this treatment. Treatments with AO-PDT were performed on 38 dogs through a narrow window of the dorsal nasal cavity. The median progression-free interval was 12 mo and recurrence was detected in 21 dogs. Based on computed tomography, recurrence in 16 dogs was biased to the following areas: lateral (n = 10), medial (n = 2), ventral (n = 0), rostral (n = 0), and caudal (n = 8). Side effects were mild and included subcutaneous emphysema and rhinitis. The median survival time was 24 mo. Although AO-PDT with cribriform irradiation is an effective treatment for intranasal tumors, AO-PDT techniques should be improved to treat the nasal cavity more uniformly and thoroughly.

Analyse de récurrence de la thérapie photodynamique peropératoire à l'acridine orange pour des chiens atteints de tumeurs intranasales. La thérapie photodynamique peropératoire à l'acridine orange (AO-PDT) et l'irradiation de la plaque cribriforme sont utilisées pour traiter les tumeurs intranasales canines. Le but de cette étude était d'évaluer les effets de l'AO-PDT sur les tumeurs intranasales et le taux de récidive des tumeurs après ce traitement. Des traitements avec AO-PDT ont été effectués sur 38 chiens à travers une fenêtre étroite de la cavité nasale dorsale. L'intervalle médian sans progression était de 12 mois et une récidive a été détectée chez 21 chiens. Sur la base de la tomodensitométrie, la récidive chez 16 chiens était biaisée dans les zones suivantes : latérale (n = 10), médiale (n = 2), ventrale (n = 0), rostrale (n = 0) et caudale (n = 8). Les effets secondaires étaient légers et comprenaient l'emphysème sous-cutané et la rhinite. La durée médiane de survie était de 24 mois. Bien que l'AO-PDT avec irradiation de la plaque cribriforme soit un traitement efficace pour les tumeurs intranasales, les techniques d'AO-PDT devraient être améliorées pour traiter la cavité nasale de manière plus uniforme et plus complète.(Traduit par Dr Serge Messier).

Intraoperative acridine orange photodynamic therapy and cribriform electron-beam irradiation for canine intranasal carcinomas: 14 cases.

Canine intranasal carcinomas are almost always malignant. Surgery alone often results in rapid tumor regrowth. Radiotherapy is the treatment of choice for dogs with intranasal tumors. Here, we retrospectively assessed treatment of intranasal carcinoma by marginal tumor resection followed by intraoperative acridine orange (AO) photodynamic therapy (PDT) and cribriform plate electron-beam intraoperative radiotherapy (IORT). Fourteen canine cases were assessed, 12 of which had stage I tumors, one with stage III, and one with stage IV. Recurrence was detected in 8, with a median recurrence from the time of treatment of 6 months (range: 3 to 16 months). The median progression-free survival time and overall survival time after treatment were 13 and 22 months, respectively. Adverse events were mild. Marginal tumor resection followed by intraoperative AO-PDT and cribriform plate electron-beam IORT may increase the tumor control time in dogs with marginally resectable intranasal malignant tumors beyond that incurred by surgery alone.

Thérapie photodynamique peropératoire à l'acridine orange et irradiation par faisceau électrique pour carcinome intranasal canin : 14 cas. Un carcinome intranasal canin est presque toujours malin. Une simple opération chirurgicale résulte souvent dans la rapide réapparition de la tumeur. Dans cet article, nous discutons d'un traitement d'un carcinome intranasal par résection marginale de la tumeur effectué simultanément à une thérapie photodynamique (TPD) peropératoire à l'acridine orange (AO) et une radiothérapie peropératoire (RPO) par faisceau électrique des lames criblées. L'étude a porté sur quatorze cas chez le chien dont 12 tumeurs étaient classées au stade I, une au stade III et une au stade IV. Huit des cas étaient des cas de récidive selon une moyenne de 6 mois depuis la période du traitement (plage de 3 à 16 mois). Le temps de survie moyen à l'état stabilisé et le temps de survie général après traitement étaient respectivement de 13 et 22 mois. Les incidents thérapeutiques sont moindres (cinq cas d'emphysème sous-cutané et quatre cas de rhinite). La résection marginale de la tumeur conduite simultanément avec une TPD-AO peropératoire et une RPO par faisceau électrique des lames criblées semble permettre une plus longue phase de maîtrise des tumeurs chez le chien porteur d'une tumeur intranasale maligne à résection marginales possible par rapport aux résultats obtenus par simple intervention chirurgicale.(Traduit par les auteurs).

Effects of three infusion fluids with different sodium chloride contents on steady-state serum concentrations of bromide in dogs.

Potassium bromide overdose (bromism) in the management of canine epilepsy has been known. However, a protocol to reduce bromide concentrations rapidly has not been previously established. The effects of three infusion fluids with different chloride contents on the steady-state serum concentrations of bromide in beagles were determined. After stabilization of the serum bromide concentrations, seven dogs were infused with saline (Na+ 154 mmol/L; Cl- 154 mmol/L), lactated Ringer's (Na+ 131 mmol/L; Cl- 110 mmol/L), or maintenance solutions (Na+ 35 mmol/L; Cl- 35 mmol/L) at a rate of 2 or 10 ml kg-1  hr-1 for 5 hr. Serum and urine were collected hourly, and the bromide concentrations were measured. When saline and lactated Ringer's solutions were infused at a rate of 10 ml kg-1  hr-1 for 5 hr, serum bromide concentrations were decreased by 14.24% and urine bromide concentrations by 17.63%, respectively. Of all compositions of infusion fluids, only sodium and chloride contents were associated with the decreased serum concentrations and the increased renal clearance of bromide. In summary, saline and lactated Ringer's solutions reduced serum bromide concentrations in a sodium chloride-dependent manner in dogs were found when infused at 10 ml kg-1  hr-1 for 5 hr.

Combination of Cilostazol and L-Carnitine Improves Walking Performance in Peripheral Arterial Disease Model Rats.

Cilostazol and L-carnitine have been used as a first-line drug and supplement, respectively, in patients with peripheral arterial disease with intermittent claudication. In this study, the effect of the combination of cilostazol and L-carnitine has been investigated in rats with unilateral hindlimb ischemia. For 28 days, cilostazol and L-carnitine were administrated separately or as a combination. The distance walked before gait disturbance developed was measured using a treadmill for 5 days a week. The capillary density of the ischemic hindlimb was evaluated by immunohistochemical staining at days 7, 14, 21, and 28. Angiogenic gene expression was measured by real-time RT-PCR at days 7 and 28. The greatest increase in the distance was observed in the combination therapy group when compared to the other groups. The capillary density in the adductor muscles of rats treated with cilostazol alone and combination therapy increased at day 28. Angiopoietin-2/Angiopoietin-1 expression ratios were higher, suggesting the promotion of angiogenesis, with cilostazol alone and combination therapy at day 7. This is the first study to show functional improvement of the hind limb following combination therapy with cilostazol and L-carnitine in experimental animals. This study also revealed that cilostazol promotes angiogenesis, and L-carnitine additively contributes to functional improvement via a non-angiogenic mechanism.

Canine Orientia tsutsugamushi infection: report of a case and its epidemicity.

A lethargic household dog was referred to a private hospital in Japan. Diagnosis was carried out by the polymerase chain reaction (PCR) method developed for human Orientia tsutsugamushi infection using the dog's anticoagulated peripheral blood. Karp, Kato and Kuroki-type genomes were detected and the dog was diagnosed with O. tsutsugamushi infection. These findings demonstrate that dogs can act as a host for O. tsutsugamushi and the PCR method developed for human beings can be used for the diagnosis of canine O. tsutsugamushi infection. A concurrent epidemiological study examined 10 asymptomatic dogs that were fed in the same area as the sick dog. Kuroki-type genome in all dogs, Gilliam-type genome in 6 dogs and Kawasaki-type genome in 3 dogs were detected. These results provide further evidence that dogs can be naturally infected with O. tsutsugamushi outdoors and that dogs play a role as a host in the lifecycle of O. tsutsugamushi.

A new bipolar precordial electrocardiographic lead configuration for specific evaluation of atrial depolarization in healthy dogs.

OBJECTIVE: The Lewis lead is an EGC configuration used to detect atrial activity and its relationship with ventricular activity. However, no equivalent configuration has been proposed in veterinary medicine. Therefore, this study explored new bipolar lead configurations to evaluate atrial depolarization and investigated their characteristics by comparing them with conventional leads. The authors hypothesized that a lead with a high absolute value of the P wave (|P|) and a high ratio of the P wave to the QRS complex (|P|/|QRS|) might be an appropriate configuration. ANIMALS: 6 laboratory Beagles were used. PROCEDURES: Electrocardiograms were recorded using bipolar limb leads (I, II, III, aVL, aVF, and aVR) and unipolar precordial leads (C2, C3, C4, C5, C6, M1, M2, M5, M6, 1st-R, CV6LL, and V10) in the standing position. The new bipolar leads were attached in the following configuration: the negative electrode was attached to M6, and the positive electrode was sequentially applied to M1 and M2. The leads were named M6M1 and M6M2. RESULTS: The waveforms obtained using the new bipolar leads M6M1 and M6M2 showed significantly higher |P|/|QRS| and |P| values than those obtained using conventional limb leads and precordial leads. CLINICAL RELEVANCE: The new leads achieved a specific enhancement of atrial activity conducted at a reduced ventricular amplitude and increased atrial amplitude, similar to the Lewis lead in human medicine. These findings suggest that M6M1 and M6M2 could be supplemental lead configurations to identify P waves without amplifying the QRS waves compared to conventional methods.

Clinical efficacy and tolerability of zonisamide monotherapy in dogs with newly diagnosed idiopathic epilepsy: Prospective open-label uncontrolled multicenter trial.

BACKGROUND: Zonisamide (ZNS) is a newer generation antiseizure medication (ASM) used to treat epilepsy in dogs and cats. However, scientific and clinical information, particularly regarding monotherapy, is limited. OBJECTIVES: To evaluate the antiseizure efficacy and tolerability of ZNS monotherapy in dogs with newly diagnosed idiopathic epilepsy (IE). ANIMALS: Study included 56 client-owned dogs newly diagnosed with IE. METHODS: This was a prospective multicenter, open-label, uncontrolled study. All dogs were ASM-naïve and had ≥2 seizures within 12 weeks. Dogs were administered 2.7-14.4 mg/kg ZNS PO q12h and followed up for ≥12 weeks. Data from the 12-week maintenance treatment period were compared with those from the 4- to 12-week pretreatment period for efficacy evaluation. Data from the entire ZNS administration period were used to assess tolerability. RESULTS: Fifty-six dogs were included in our study. Of the dogs, 53 were assessed for efficacy; 40 (76%) had a ≥ 50% reduction in seizure frequency, and 29 (55%) achieved seizure freedom. For 90% of the dogs with ≥50% reduction in seizure frequency, the mean ZNS dose was 4.8 (range, 2.7-8.6) mg/kg q12h and the mean trough plasma ZNS concentration was 18.9 (range, 8.0-48.0) µg/mL. In 7 of the 56 dogs (13%), reduced activity, decreased appetite, vomiting, hindlimb weakness, soft stools, or constipation was observed, albeit mild and temporary. Laboratory tests revealed no relevant changes. CONCLUSIONS AND CLINICAL IMPORTANCE: Our study suggests that ZNS monotherapy is effective and well-tolerated in dogs with newly diagnosed IE.

Measurement of Carbonic Anhydrase I and II Isozymes in Feces as a Marker of Occult Blood in Horses with Intestinal Tract Bleeding.

Although endoscopy is the definitive diagnostic method for the detection of colonic ulcers, the equipment required for performing the test is costly and difficult to use. Therefore, a simple cost-effective and reliable screening test for intestinal tract bleeding is needed. To this end, we measured carbonic anhydrase isozymes (CA-I and CA-II) originating from erythrocytes by ELISA in order to determine if they could be used as markers of occult blood in feces. For fecal extract preparation, 2 g of feces were mixed with 4 ml of 0.01 M Tris-HCl (pH 8.0) containing 0.01% thimerosal. The concentrations of CA-I and CA-II in the fecal samples of 13 clinically normal racehorses were found to be 30.0 ± 10.0 and 34.0 ± 13.0 ng/ml, respectively. Increased concentrations of CA-I were detected in the fecal samples of 5 horses after blood administration; however, no increase was observed in CA-II. The concentrations of CA-I and CA-II in the fecal samples of 88 racehorses with clinical signs of equine gastric ulcer syndrome (EGUS) were 115.3 ± 79.0 and 41.0 ± 42.0 ng/ml, respectively. Thus, our results indicate that CA isozymes can be useful as markers of occult blood in the fecal samples of horses with intestinal tract bleeding.

Booster effect of canine distemper, canine parvovirus infection and infectious canine hepatitis combination vaccine in domesticated adult dogs.

Domesticated adult dogs with antibody titer classified as below 'high' to one or more of canine distemper virus (CDV), canine parvovirus type-2 (CPV-2) and canine adenovirus type-1 (CAdV-1) were then given an additional inoculation, and the effectiveness of this booster evaluated 2 months later. Consequently, CDV and CAdV-1 antibody titer experienced a significant increase, but the same effect was not observed in the antibody titer of CPV-2. These findings suggest that with additional inoculation, a booster effect may be expected in increasing antibody titers for CDV and CAdV-1, but it is unlikely to give an increase in CPV-2 antibody titer.

Repeated-Dose Pharmacodynamics of Pimobendan in Healthy Cats.

The aims of this study were to investigate the effects of repeated and multiple-dose pimobendan on cardiac systolic function and the correlations between changes in cardiac systolic function and plasma concentrations of pimobendan and O-desmethylpimobendan (ODMP). Five clinically healthy cats were subjected to four different medication protocols for 14 days, with a washout period of at least 1 month between each protocol. The protocols were pimobendan 0.5 mg/kg q12h (high dosage [HD] group); pimobendan 0.25 mg/kg q12h (standard dosage [SD] group); pimobendan 0.125 mg/kg q12h (low dosage group); and Biofermin R, one tablet q12h (placebo group). Echocardiography and measurement of plasma concentrations of pimobendan and ODMP were performed prior to medication administration (baseline) and 20, 40, 60, 120, 240, 360, and 480 min after administration, and the correlation between the changes in cardiac systolic function and plasma concentration of pimobendan, ODMP, or the sum of both were examined. The cardiac systolic function increased in the HD and SD groups, and there were significant correlations between the lateral peak systolic myocardial velocity (S') changes and plasma pimobendan, plasma ODMP, and the sum of both. Repeated doses of pimobendan in healthy cats increased cardiac systolic function, and there were significant correlations between cardiac function and plasma concentrations of pimobendan and ODMP. The results of this study highlight the effectiveness of a higher dose of pimobendan.

Involvement of neurokinin-1 receptors in the autonomic nervous system in colorectal distension-induced cardiovascular suppression in rats.

Situational syncope, which includes rectally mediated reflexes, is defined as syncope induced by a specific situation. Its pathogenesis generally involves disorders of the autonomic nervous system. However, the mechanisms and preventive strategies are not yet well understood. Therefore, we hypothesized that a tachykinin neurokinin-1 receptor might be involved in the autonomic nervous system, and that a neurokinin-1 receptor antagonist could mitigate reflex syncope. This study used a rat model in which the reflex was induced by afferent vagal stimulation with colorectal distension (CRD). In the study, the rats were divided into three groups: non-CRD, CRD, and CRD with a neurokinin-1 receptor antagonist. First, we examined the effect of fosaprepitant, a neurokinin-1 receptor antagonist, on the circulatory response in this model. We then determined the brain regions that showed increased numbers of c-Fos immunoreactive cells in the respective groups. Our results suggest that the colorectal distension procedure reduced blood pressure and that fosaprepitant lowered this response. In addition, the number of c-Fos immunoreactive cells was increased in the caudal ventrolateral medullary region with colorectal distension, and this number was decreased by the administration of fosaprepitant. In conclusion, fosaprepitant might be involved in the vagal reflex pathway and potentially suppress the circulatory response to colorectal distension.

Somatosensory evoked potentials of the tibial nerve during the surgical decompression of thoracolumbar intervertebral disk herniation in dogs.

This study aimed to identify the impact on spinal cord integrity and determine the electrophysiological safety level during surgery for thoracolumbar intervertebral disk herniation in dogs. A total of 52 dogs diagnosed with thoracolumbar intervertebral disk herniation were enrolled. The tibial nerve somatosensory evoked potential elicited on the scalp by stimulation of the tibial nerve was recorded before and during hemilaminectomy. Both the amplitude and latency of the somatosensory evoked potential were periodically registered, and the percentage changes from the pre-operative control values (amplitude rate and latency rate) were calculated. When the multifidus muscles were retracted after removal from the spinous processes and vertebrae, the somatosensory evoked potential amplitude rate decreased in all dogs, while the latency rate increased in 33 dogs examined. The amplitude rate remained unchanged during the halting procedure, loosening retraction, and hemilaminectomy. After removing the disc material from the spinal canal, the amplitude rate was increased. The somatosensory evoked potential latency increased when the multifidus muscles were retracted and shortened after multifidus muscles closure in four cases. The outcome of all cases showed improvement in clinical signs 7 days after operation. Spinal cord conduction is impaired by retraction of the multifidus muscles and improved by removal of disk materials. Maintaining intraoperative SEP amplitudes above 50% of control may help avoid additional spinal cord injury during surgery. Since we have no case that worsened after the surgery, however, further studies are necessary to confirm this proposal.

Antibody titers for canine parvovirus type-2, canine distemper virus, and canine adenovirus type-1 in adult household dogs.

Serum antibody titers for canine parvovirus type-2 (CPV-2), canine distemper virus (CDV) and canine adenovirus type-1 (CAV-1) were investigated in 1031 healthy adult household dogs (2 to 18 years old) given an annual inoculation in the previous 11 to 13 months. The number of dogs retaining significant titers of antibodies against CPV-2, CDV, and CAV-1 were 888 (86%), 744 (72%), and 732 (71%), respectively. There were no differences between males and females in antibody titers against the 3 viruses. Antibody titer for CPV-2 was significantly higher in younger dogs than in older dogs, CDV antibody was significantly higher in older dogs than in younger dogs, and CAV titer was not associated with age.

Serum concentration and safety of intravenous drip versus subcutaneous administration of carboplatin in dogs.

Carboplatin is used to treat certain cancers in dogs and cats and is routinely administered via intravenous drip (IVD). Subcutaneous (SC) administration has also been described. However, the toxicity, serum concentrations, and area under blood concentration-time curves (AUCs) of SC carboplatin are unknown. This study aimed to compare serum carboplatin concentrations in dogs after SC and IVD and to monitor any adverse events. In this crossover study, five dogs received SC or IV carboplatin (300 mg/m2). After a minimum of 3 weeks, each dog received the other treatment. No gross skin toxicity or abnormal clinical signs were observed in any of the dogs. Blood test abnormalities were detected in most dogs. Decreased neutrophil and platelet counts, and increased C-reactive protein (CRP) levels were found. There was no significant difference in the neutropenia, thrombocytopenia, and CRP scores between the groups. Systemic toxicities of SC carboplatin were comparable to those of IVD carboplatin. The time to maximum carboplatin concentration after SC was longer than that after IVD (P<0.001). SC carboplatin remained in the serum longer than IVD carboplatin (P=0.008). The AUC of SC was less than that of IVD (P=0.002). The AUC and time taken to reach the maximum concentration of SC carboplatin were lower than those of IVD carboplatin. This study suggests that SC carboplatin may be an efficacious option for the treatment of tumors in dogs, particularly where IVD administration is challenging.

Safety of alternate-day treatment with TS-1TM (tegafur/gimeracil/oteracil) in tumor-bearing dogs: a pilot study.

Tegafur is a prodrug of fluoropyrimidine 5-fluorouracil (5-FU), while TS-1TM is an oral fixed-dose combination of three active drugs, tegafur, gimeracil, and oteracil. This pilot study evaluated the safety of tegafur/gimeracil/oteracil in the treatment of cancers in dogs. Tegafur/gimeracil/oteracil was administered orally at a mean dose of 1.1 mg/kg twice daily on alternate days, Monday-Wednesday-Friday, every week to 11 dogs with tumors. Partial response and stable disease were observed in one dog each, whereas six exhibited progressive disease. Three dogs were not assessed. Adverse events, the most serious being grade 2, were noted in seven dogs. Adverse events were acceptable, and the drug was effective in some dogs. Therefore, tegafur/gimeracil/oteracil may be useful for treating malignant solid tumors in canines.

F-wave parameters for the tibial nerve in Miniature Dachshunds with and without naturally acquired thoracolumbar intervertebral disk herniation.

OBJECTIVE: To determine values of F-wave parameters for the tibial nerve in clinically normal Miniature Dachshunds and those with thoracolumbar intervertebral disk herniation (IVDH). ANIMALS: 53 Miniature Dachshunds (10 clinically normal and 43 with various clinical grades of thoracolumbar IVDH). PROCEDURES: F-waves were elicited in the interosseous muscles of 1 hind limb in each dog by stimulation of the tibial nerve. F-wave parameters were measured for 32 stimuli/dog, and mean values were calculated. Linear regression was performed to assess correlations between F-wave parameters and clinical severity of IVDH. RESULTS: For clinically normal dogs, mean ± SD values of shortest F-wave latency, mean F-wave conduction velocity, mean F-wave duration, and ratio of the mean F-wave amplitude to M response amplitude were 8.6 ± 0.6 milliseconds, 83.7 ± 6.1 m/s, 6.6 ± 1.5 milliseconds, and 9.8 ± 8.5%, respectively. F-wave persistence was 100%. Mean F-wave duration was positively correlated with clinical grade of IVDH. Linear regression yielded the following regression equation: F-wave duration (milliseconds) = 6.0 + 2.7 × IVDH grade. One dog with grade 2 IVDH had a mean F-wave duration shorter than that of all 5 dogs with grade 1 IVDH; 1 dog with grade 3 IVDH had a longer duration than that of all 10 dogs with grade 4 IVDH. CONCLUSIONS AND CLINICAL RELEVANCE: Mean F-wave duration was correlated with the severity of inhibitory motor tract dysfunction in the spinal cord of dogs. F-wave examination may be useful for objective functional evaluation of upper motor neurons in the spinal cord.

Characteristic behavioral anomalies in rats prenatally exposed to 5-bromo-2'-deoxyuridine.

The aim of the present study was to characterize behavioral anomalies in rats prenatally exposed to 5-bromo-2'-deoxyuridine, a useful model of hyperactive disorder. Rats were treated with BrdU at 50mg/kg IP or carboxymethylcellulose, its vehicle, on gestational Days 9 through 15, and their offsprings were subjected to behavioral tests. Rats prenatally exposed to 5-bromo-2'-deoxyuridine showed higher locomotor activity levels when the lights were turned off, and these levels kept increasing throughout the dark cycle. In an elevated plus maze, the rats prenatally exposed to 5-bromo-2'-deoxyuridine exhibited decreased anxiety-related behavior, including higher open arm entries and a longer time spent per one open arm entry when compared with rats prenatally exposed to carboxymethylcellulose. Methylphenidate, a psychostimulant that suppresses hyperactivity in humans with attention-deficit hyperactivity disorder, increased locomotor activity in both rats, with a greater sensitivity in rats prenatally exposed to 5-bromo-2'-deoxyuridine. Desipramine, a specific noradrenaline uptake inhibitor, normalized the hyperactivity of rats prenatally exposed to 5-bromo-2'-deoxyuridine. Paroxetine, a selective serotonin reuptake inhibitor, also normalized the hyperactivity and the low anxiety-related behavior in the elevated plus maze. These results suggest that rats prenatally exposed to 5-bromo-2'-deoxyuridine are hyperactive and exhibit a lower anxiety level. Dysfunctional monoaminergic neurons may be, at least in part, the cause of the behavioral anomalies.

Therapeutic time window of cannabidiol treatment on delayed ischemic damage via high-mobility group box1-inhibiting mechanism.

Cannabidiol decreases cerebral infarction and high-mobility group box1 (HMGB1) in plasma in ischemic early phase. However, plasma HMGB1 levels in ischemic delayed phase reach higher concentration with the progressing brain injury. In this study, we investigated the therapeutic time window of cannabidiol on functional deficits, glial HMGB1 and plasma HMGB1 levels in a 4 h mouse middle cerebral artery (MCA) occlusion model. Cannabidiol-treated mice were divided into 3 groups as follows: group (a) treated from day 1, group (b) treated from day 3, group (c) treated from day 5 after MCA occlusion. Moreover, minocycline, microglia inhibitor, and fluorocitrate, an inhibitor of astroglial metabolism, were used to compare with cannabidiol-treated group. Repeated treatment with cannabidiol from 1 and 3 d at the latest after cerebral ischemia improved functional deficits and survival rates. However, cannabidiol from 5 d could not improve the ischemic damage as well as fluorocitrate-treated group. Moreover, both group (a), group (b) and minocycline but not group (c) and fluorocitrate-treated group had a decrease in the number of Iba1 expressing HMGB1 positive cells and HMGB1 levels in plasma. Cannabidiol may provide therapeutic possibilities for the progressing brain injury via HMGB1-inhibiting mechanism.

Electroacupuncture improves neuronal function by stimulation of ascending peripheral nerve conduction in rats with spinal cord injury.

OBJECTIVE: To establish a method of transient sciatic nerve blockade and to examine the involvement of the ascending peripheral nerve pathway in the therapeutic effect of electroacupuncture at Zusanli (ST 36) in rats with spinal cord injury (SCI). METHODS: We examined the transient effect of daily lidocaine administration into the posteromedial part of the greater trochanter on sciatic nerve function using electrophysiological examination and histopathology of the sciatic nerve. Rats were divided into three groups: an SCI group (SCI without treatment), an SCI with electroacupuncture treatment (SCI-EA) group, and an SCI with nerve block and electroacupuncture (SCI-NB-EA) group (nerve block was achieved by lidocaine administration to transiently block the ascending peripheral nerve pathway). Behavioral tests and electrophysiological examinations were performed to evaluate recovery of neurological function. RESULTS: Sciatic nerve conduction was normal immediately before daily lidocaine administration. Histopathological analysis also indicated normal sciatic nerve, confirming that lidocaine nerve blockade was suitable and reversible for transiently eliminating nerve transmission. Neurological function in the SCI-EA group was superior to that in the SCI group, while no differences were found between the SCI and SCI-NB-EA groups. CONCLUSION: Electroacupuncture treatment can promote recovery of neurological function. Facilitation of nerve conduction may play an important role in this recovery.