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GABAergic intercalated neurons of amygdala (ITCs) have recently been shown to be important in the suppression of fear-like behavior. Effects of ECa233 (a standardized extract of Centella asiatica), previously demonstrated anxiolytic activity, were then investigated on ITCs. Cluster of GABAergic neurons expressing fluorescence of GFP was identified in GAD67-GFP knock-in mice. We found that neurons of medial paracapsular ITC were GABAergic neurons exhibiting certain intrinsic electrophysiological properties similar to those demonstrated by ITC neurons at the same location in C57BL/6J mice. Therefore, we conducted experiments in both C57BL/6J mice and GAD67-GFP knock-in mice. Excitatory postsynaptic currents (EPSCs) were evoked by stimulation of the external capsule during the whole cell patch-clamp recordings from ITC neurons in brain slices. ECa233 was found to increase the EPSC peak amplitude in the ITC neurons by about 120%. The EPSCs in ITC neurons were completely abolished by the application of an AMPA receptor antagonist. Morphological assessment of the ITC neurons with biocytin demonstrated that most axons of the recorded neurons innervated the central nucleus of the amygdala (CeA). Therefore, it is highly likely that anxiolytic activity of ECa233 was mediated by increasing activation, via AMPA receptors, of excitatory synaptic input to the GABAergic ITC leading to depression of CeA neurons.

We investigated ascending somatosensory pathways in neonatally hemidecorticated rats. Injection of an anterograde tracer, biotinylated dextran amine (BDA), into the contralesional dorsal root ganglions revealed ipsilateral projections to the dorsal column nuclei (DCN) in hemidecorticated rats as well as in normal rats. Injection of BDA into the DCN on the same side revealed that while most axons projected to the contralateral thalamus, some axons were detected in the ipsilateral thalamus in hemidecorticated rats while such projections were rarely detected in normal rats. The results suggest that aberrant ipsilateral projections of DCN neurons contralateral to the lesion developed after the hemidecortication.

1. ECa 233, the standardised extract of Centella asiatica, contains not less than 80% triterpenoid glycosides, in a madecassoside:asiaticoside ratio of 1.5 (±0.5):1. 2. The pharmacokinetic comparison of madecassoside and asiaticoside was performed in rats following intravenous and oral administration of ECa 233, or an equivalent dose of the individual compounds. Blood, tissues, urine and faeces were collected after dosing to determine drug and metabolite levels using liquid chromatography-tandem mass spectrometry. 3. Our study demonstrated that plasma levels of madecassoside, and to a lesser extent asiaticoside, were higher after administration of ECa 233 than the corresponding values for the pure compounds. There was a bidirectional interconversion between asiaticoside and madecassoside consistent with the increased exposure of madecassoside and asiaticoside in ECa 233. 4. Both madecassoside and asiaticoside appeared to be widely distributed in several organs and metabolized extensively; following intravenous administration of either compound, approximately 80-90% of the dose was recovered as madecassic acid and asiatic acid in the faeces.

ECa 233, a standardized extract of Centella asiatica, has been found to exhibit various positive neurological effects and to have a good safety profile. The present study aimed to explore the disposition kinetics of ECa 233, containing madecassoside (53.1 %) and asiaticoside (32.3 %), in rats. The extract was intravenously or orally administered at doses from 50 to 200 mg/kg. Plasma, tissues, urine, and feces were collected at time points from 0 to 48 h after dosing. The levels of madecassoside and asiaticoside, as well as their postulated triterpenic metabolites, madecassic acid and asiatic acid, in biological samples, were simultaneously measured by liquid chromatography-tandem mass spectrometry. The results showed that all animals had a good tolerability for ECa 233, whereas madecassic and asiatic acids were found in negligible amounts after pharmacokinetic assessment. Madecassoside and asiaticoside demonstrated rather similar absorption and tissue distribution profiles. They were rapidly absorbed, reaching maximum levels within 5–15 min after oral administration, but they had poor oral bioavailability, less than 1 %. Both triterpenoids were extensively distributed in the brain, stomach, and skin within 1 h and remained there for at least 4 h after dosing. Madecassoside and asiaticoside in ECa 233 were mainly excreted as an unchanged form after being injected, and exclusively as triterpenic acid metabolites in feces after oral administration. The pharmacokinetic results obtained could provide some guidance for an appropriate dosing regimen of ECa 233 in future studies. This study also provided the first evidence demonstrating the presence of madecassoside and asiaticoside in their target tissues.

Aim of the study γ-Mangostin is a xanthone found in the fruit hulls of Garcinia mangostana L., which have long been used in Southeast Asia as a traditional medicine for the treatment of abdominal pain, dysentery, wound infections, fever and convulsions. Recent studies have revealed that γ-mangostin exhibits a variety of pharmacological activities, including serotonin 2 (5-HT2) receptor antagonism, anti-inflammatory effects and analgesic effects. To explore the mechanism of γ-mangostin responsible for these pharmacological activities, especially its effects on some related receptors, we investigated the effects of γ-mangostin on 5-HT2, histamine (H1) and bradykinin (BK2) receptor gene expression in neuroblastoma (NG 108-15) cells in vitro. Additionally, to extend the study of the pharmacological properties, we examined the effect of γ-mangostin on the muscarinic (M4) receptor. Materials and methods NG 108-15 cells were cultured in vitro and treated with γ-mangostin or a 5-HT2 receptor antagonist (either imipramine or ketanserin). Then, the levels of mRNA for 5-HT2A/2C receptors were evaluated by semi-quantitative RT-PCR. The preventive effect of serotonin on the enhancement effects was also revealed. Additionally, the effects of γ-mangostin on the muscarinic, histamine and bradykinin receptors were determined. Results Chronic application of γ-mangostin at a concentration of 0.1 μM induced a significant increase in the level of 5-HT2A/2C receptor mRNA. These effects were prevented by serotonin. Moreover, γ-mangostin up-regulated the M4, H1 and BK2 receptors. Conclusion The ability of γ-mangostin to enhance the expression of 5-HT2A/2C, muscarinic, histamine and bradykinin receptor mRNA suggests that this compound has antagonistic effects. These pharmacological properties may partly account for the benefits of using mangosteen in the treatment of inflammation, pain and neuropsychiatric symptoms.

Background: N(2-propylpentanoyl) urea (VPU) is a new valproic acid (VPA) analog with higher anticonvulsant activity than its parent compound in various animal models including seizure acutely induced by pilocarpine. Objective: Investigate its effects on hippocampal amino acid neurotransmitters in spontaneous recurrent seizure (SRS) rats. Methods: Pilocarpine hydrochloride was used to induce status epilepticus (SE). Animals were visually observed for two hours/day for an episode of SRS for six weeks. Microdialysis experiment was performed to detect hippocampal amino acid neurotransmitters on those rats that developed SRS. Results: In comparison to normal rats, hippocampal glutamate, gamma-aminobutyric acid (GABA), and glycine, significantly increased in SRS rats. Occurrence of SRS in the faces of increased level of inhibitory neurotransmitters suggests the key role played by glutamate in the genesis and control of SRS. Based on the observation in pilocarpine-induced SE, the level of glutamate in SRS rats significantly decreased by a clinically effective anticonvulsant, VPA (300 and 600 mg/kg, i.p). Similar profile on hippocampal glutamate was also exhibited by VPU (50 and 100 mg/kg, i.p.). Conclusion: The possible role of VPU in controlling seizure in SRS rats and subsequently human temporal lobe epilepsy as VPA was suggested.

The pattern of motoneuronal projection and termination of single C3-C4 propriospinal neurones in the forelimb segments C6-T1 of the cat was investigated by intra-axonal injection of horseradish peroxidase into stem axons. Twelve well-stained axons were used for analysis. Termination was observed in the estimated location of motor nuclei innervating pure shoulder muscles in 10 cases. Among motoneurones innervating shoulder, elbow, wrist, and digit muscles, projection and termination were observed in motor nuclei controlling muscles of two or three joints in the following combinations: shoulder + elbow, shoulder + wrist, shoulder + elbow + wrist, shoulder + elbow + digit, and elbow + wrist + digit. In one case it was difficult to exclude the possibility of projection and termination in motor nuclei controlling muscles at all four joints. These patterns of motoneuronal projection from C3-C4 propriospinal neurones are compatible with their function in mediating the descending command for visually guided target reaching movements with the forelimb. In addition, it was found that the C3-C4 propriospinal neurones project and terminate in the region of ventral and ventromedial motor nuclei, which innervate axial muscles acting on the trunk. This was confirmed by intracellular recording from presumed ventromedial motoneurones in the C6-C7 segments. It is postulated that the C3-C4 propriospinal neurones, in addition to their control of forelimb movements, provide for conjoint control of axial muscles to stabilize the trunk during target reaching.

Background The efficacy of Centella asiatica for incision and burn wounds are not fully understood. Here, we report the wound healing activities of sequential hexane, ethyl acetate, methanol, and water extracts of Centella asiatica in incision and partial-thickness burn wound models in rats. Methods Male Sprague–Dawley rats weighing 250–300 g were randomly divided into incision and burn wound groups. Each group was stratified into seven subgroups: (1) untreated; (2) NSS-; (3) Tween 20®- (vehicle control); (4) hexane extract-; (5) ethyl acetate extract-; (6) methanol extract-; and (7) aqueous extract-treated groups. The test substances were applied topically once daily. The tensile strength of the incision wound was measured on the seventh day after wound infliction. The general appearance and degree of wound healing of the burn wound were assessed on Days 3, 7, 10 and 14 after burn injury and prior to histopathological evaluation. Results On the seventh day after wound infliction, the tensile strength of incision wound in all extract-treated groups was significantly higher than that of the vehicle control (Tween 20®), but comparable to the NSS-treated group. The degrees of healing in the burn wound with the four extracts were significantly higher than that of the control on Days 3, 10 and 14. Histopathological findings on Day 14 after burn injury revealed prominent fibrinoid necrosis and incomplete epithelialization in the control and untreated groups, whereas fully developed epithelialization and keratinization were observed in all extract-treated groups. Analysis by thin layer chromatography demonstrated that the phyto-constituents β-sitosterol, asiatic acid, and asiaticoside and madecassocide were present in the hexane, ethyl acetate and methanol extracts, respectively. Conclusions All extracts of Centella asiatica facilitate the wound healing process in both incision and burn wounds. Asiatic acid in the ethyl acetate extract seemed to be the most active component for healing the wound.

Ethnopharmacological relevance Centella asiatica has long been used for various neurological disturbances in Southeast Asian countries. The present study aims to demonstrate the anxiolytic effect of ECa 233, a standardized extract of C. asiatica containing triterpenoids not less than 80%, in comparison to diazepam. Materials and methods The test compound was given orally to non-stressed mice and mice subjected to chronic immobilization stress. Anxiolytic effect was assessed by an elevated plus maze (EPM), a dark-light box and an open-field tests. Results Anxiolytic effect of ECa 233 was clearly demonstrated in non-stressed mice subjected to acute stress in all behavioral tests employed. In the EPM test, chronically stressed mice showed significant decrease in the number of open arm entries, shortening the time spent in open arms and an increase of the latency to leave the central area, suggesting their release from the stress. In addition, ameliorating effect of ECa 233 was observed on the body weight and serum corticosterone which were adversely affected by immobilization stress. Madecassoside and asiaticoside, equal to their respective contents of the effective doses of ECa 233, exclusively presented anxiolytic effects in EPM, while no distinct effect was observed on the body weight and serum corticosterone. Conclusions The present study demonstrated anxiolytic effect of ECa 233 in both acutely and chronically stressed animals. These effects could be mainly accounted by madecassoside and asiaticoside, suggesting a possible use of ECa 233 for the treatment of both acute and chronic anxiety in the pathological state.

Extra- and intracellular recording was made from neurones in laminae VII and VIII of the C6-Th1 segments, which were disynaptically excited from the contralateral pyramid, nucleus ruber and monosynaptically from the ipsilateral lateral reticular nucleus. The results suggest collateral excitation from the C3–C4 propriospinal neurones which are excited monosynaptically from the former two inputs and antidromically from the latter nucleus. The cells were antidromically activated from the ipsilateral nucleus fastigius, and from the ipsilateral or contralateral reticular formation. Some of the spinocerebellar and spinoreticular neurones were also antidromically activated from Th13. It is suggested that spinocerebellar, spinoreticular and bifurcating spinocerebellar and spinoreticular neurones receive collateral input from the same excitatory C3–C4 propriospinal neurones which project to motoneurones and/or Ia inhibitory interneurones.

Summary The present study aimed to investigate the anticonvulsant activity as well as the effects on the level of hippocampal amino acid neurotransmitters (glutamate, aspartate, glycine and GABA) of N-(2-propylpentanoyl)urea (VPU) in comparison to its parent compound, valproic acid (VPA). VPU was more potent than VPA, exhibiting the median effective dose (ED50) of 49 mg/kg in protecting rats against pilocarpine-induced seizure whereas the corresponding value for VPA was 322 mg/kg. In vivo microdialysis demonstrated that an intraperitoneal administration of pilocarpine induced a pronounced increment of hippocampal glutamate and aspartate whereas no significant change was observed on the level of glycine and GABA. Pretreatment with either VPU (50 and 100 mg/kg) or VPA (300 and 600 mg/kg) completely abolished pilocarpine-evoked increases in extracellular glutamate and aspartate. In addition, a statistically significant reduction was also observed on the level of GABA and glycine but less than a drastic reduction of glutamate and aspartate level. Based on the finding that VPU and VPA could protect the animals against pilocarpine-induced seizure it is suggested that the reduction of inhibitory amino acid neurotransmitters was comparatively minor and offset by a pronounced reduction of glutamate and aspartate. Therefore, like VPA, the finding that VPU could drastically reduce pilocarpine-induced increases in glutamate and aspartate should account, at least partly, for its anticonvulsant activity observed in pilocarpine-induced seizure in experimental animals. Some other mechanism than those being reported herein should be further investigated.

To investigate interaction between orally given Centella asiatica's ethyl acetate fraction (EACA) and intraperitoneally administered antiepileptic drugs (AEDs), namely, phenytoin, valproate and gabapentin.Isobolographic analysis was used to evaluate the interaction between EACA and AEDs in terms of protection of mice in the pentylenetetrazole test. Rotarod test was used to evaluate neurotoxicity.When given alone, the median effective dose of phenytoin, valproate and gabapentin were found to be 13, 104, and 310 mg/kg BW, respectively, whereas the corresponding values in the presence of EACA were 5, 29 and 79 mg/kg BW. Together with isobolographic analysis, the results obtained indicated an additive effect among all combinations tested. In relation to neurotoxicity, combination of gabapentin and EACA demonstrated a broader margin between the effective dose and the neurotoxic dose while the other two combinations did not.The present finding suggested a potential of Centella asiatica to be developed as an adjunctive medication for epileptic patients.

Starting from amino(di)azines and 2-chloro-6-methyliso(thio)cyanate a series of aryl-substituted urea and thiourea derivatives was prepared and screened as potential antiepileptics. Among the new derivatives tested, only 2b and 3c exhibited adequate anticonvulsant effects, whereas 3d and 4d were found to be convulsants per se.

Trajectory formation of unrestrained forelimb target-reaching was investigated in relation to the effect of a change in target location. Sagittal displacement of the target (6 cm in each direction) gave a selective change of velocity in the x direction (protraction) with an increase or decrease at larger and shorter distances, respectively. In the case of a double-peaked x velocity profile, the change was mainly with respect to the first major component. The shape of the y (sideways) and of the z (lifting) velocity profiles were both almost unchanged, but the onset of the movement in the z direction changed with the x distance. Vertical displacement (4 cm up or 5 cm down) gave increased velocity in the z direction (lifting) when the target was above the normal mid-position and decreased velocity when the target was lower. The velocity was changed with constant rate of rise, so that the rise time increased when the target was elevated and shortened when the target was lowered (pulse width control policy). The change in the z velocity was not selective. In cats with a double-peaked x velocity profile, the second component decreased when the target was elevated and increased when it was lowered. With excessive lowering of the target (14 cm down), the first x velocity component was very much reduced in amplitude so that protraction depended mainly on the second x velocity component. In the cat with a unimodal x velocity profile, a second component appeared in the x and net velocity profiles when the target was excessively lowered.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to test the working hypothesis that motor deficits after low pyramidotomy may be due to transection of the cortico-cuneate pathway, a low pyramidotomy was made 2-4 months after a C2 dorsal column (DC) transection and tested on forelimb target-reaching and food-taking. Since food-taking recovered faster than after pyramidotomy alone, it is inferred that the loss of food-taking after pyramidotomy without previous DC transection is due mainly to transection of the cortico-cuneate pathway which controls transmission from forelimb Ia afferents to the motor cortex. The dysmetria and dyscoordination of target-reaching, on the other hand, was similar whether or not the low pyramidotomy was made after a previous C2 DC transection. It is tentatively suggested that dysmetria and dyscoordination of target-reaching after pyramidotomy may be due to transection of the pathway from the motor cortex which controls spinocerebellar transmission by its effect on the lateral reticular nucleus.

Summary. The morphology of single C3-C4 propriospihal neurones (PNs) including the cell body, dendritic tree, axonal trajectory and the pattern of projection and termination of axonal collaterals in the C3-C4 segments was investigated by intra-somatic or intra-axonal injection of horseradish peroxidase. All the C3-C4 PNs could be antidromically activated from the lateral funicle in C6 and the lateral reticular nucleus but not from Thl3. Another criterion was that they received monosynaptic excitation from corticospinal fibres in the contralateral pyramid. Twenty-four C3-C4 PNs were successfully stained. They were located in the lateral part of laminae VI-VIII except for two neurones which were located in lamina V and two in lamina IX. Five to eleven dendrites originated from the cell bodies and extended throughout laminae IV-VIII and even into the white matter in the transverse plane and up to 3 mm rostro-caudally. The axonal trajectory from the cell body was usually curved before reaching the lateral funicle. The bifurcation of the stem axon into a descending and an ascending branch was mostly observed in the white matter close to or at the border between the white and grey matter at the level of the cell body. The ascending and descending axonal branches maintained their location in the same part of the lateral funicle. Sixteen out of 24 stem axons gave off collaterals in the grey matter and/or in the white matter. One to five collaterals were given off from the axons in the grey matter. Boutons were found in a restricted region in the intermediate zone from lamina VI to the border between laminae VII and VIII, in the lateral part of laminae V-IX, in the middle and medial parts of laminae VI-VIII. The termination in the vicinity of large neurones in lamina VIII suggests that long PNs receive collateral projections from the C3-C4 PNs. The finding that some collaterals terminated laterally in lamina IX is

1. The effect of stimulating the contralateral pyramid has been investigated with intracellular recording from 128 long propriospinal neurones (long PNs) in the C3-Th1 segments of the cat. Long PNs were identified by the antidromic activation from the Th13 segment. They were located in laminae VII–VIII of Rexed. Single pyramidal stimulation evoked monosynaptic EPSPs in 15/40 of the long PNs in cats with intact pyramid. In 15 other long PNs, a train of three to four pyramidal stimuli evoked EPSPs with latencies indicating a minimal disynaptic linkage. The remaining 25% of the long PNs lacked mono- or disynaptic pyramidal EPSPs. In a few cases longer latency excitation was observed. 2. The location of the intercalated neurones which mediate the disynaptic pyramidal EPSPs was investigated by making four different lesions of the corticofugal fibres: 1) at the border of the C5 and C6 segments, 2) at the border of the C2 and C3 segments, 3) at the caudal part of the pyramid; three mm rostral to the decussation and 4) at the level of the trapezoid body. Stimulation of the corticofugal fibres was made either rostral to lesion 3 (rPyr) in order to activate neurones in a cortico-bulbospinal pathway or caudal to lesion 3 (cPyr) to activate neurones in a corticospinal pathway. In the former case, in one experiment, stimulation was made in the pyramid between lesions 3 and 4 (double pyramidal lesion). In case of cPyr stimulation, lesions 1 and 2 were added sequentially in order to investigate if the corticospinal excitation was mediated via C3–C4 PNs. All lesions were made mechanically, except lesion 2 which in some of the experiments was performed by reversible cooling. 3. Stimulation in the pyramid rostral to lesion 3 and in between lesions 3 and 4 evoked disynaptic EPSPs in the long PNs, which shows that they were mediated via reticulospinal neurones. Stimulation in cPyr after lesion 3 elicited disynaptic EPSPs, which remained after lesion 1 but were abolished after adding lesion 2. It is concluded that the disynaptic cPyr EPSPs were mediated via intercalated neurones in the C3–C4 segments. 4. When the disynaptic cPyr EPSP was conditioned with a single volley in nucleus ruber and/or in tectum, it was markedly facilitated, especially when the conditioned volley was applied simultaneously with the effective cPyr volley. The results show that the intercalated neurones in the C3–C4 segments receive monosynaptic convergence from cortico-, rubro- and tectospinal] fibres. Stimulation in the lateral reticular nucleus (LRN) evoked monosynaptic EPSPs. These EPSPs had similar latencies and shapes as those previously recorded in forelimb motoneurones and which have been shown to be due to activation of ascending branches of the C3–C4 PNs. This finding in addition to the striking similarity of the descending input pattern of long PNs as compared to the forelimb motoneurones strongly suggest that short C3–C4 PNs project both to long PNs as well as to forelimb motoneurones. 5. Spatial facilitation of disynaptic EPSPs in long PNs was also observed between rPyr volleys and tectal volleys. The results suggest that common reticulospinal neurones which project to the long PNs receive monosynaptic convergence from corticofugal and tectofugal fibres but in some of the reticulospinal neurones the main input is cortical and in others tectal. Monosynaptic EPSPs were evoked from the medial part of the reticular formation, from 2 mm caudal to 6 mm rostral of the obex level. These EPSPs were presumably due to direct activation of reticulospinal neurones. 6. Convergence of disynaptic excitation mediated by cortico-propriospinal and cortico-reticulospinal routes was observed in about 12% of the long PNs. Convergence of monosynaptic corticospinal and disynaptic corticoreticulospinal and/or cortico-propriospinal input was observed in about 15% of the long PNs. 7. The role of the monosynaptic pyramidal input and disynaptic corticoreticulospinal and cortico-propriospinal (mediated by short C3–C4 PNs) inputs to long PNs is discussed in relation to postural control during movements of head and forelimb.

Intracellular recording and injection of horseradish peroxidase (HRP) were made in neurones located medially in lamina VII and in lamina VIII of the forelimb segments (C6-Th1). The cells received disynaptic excitation from the contralateral pyramid after corticospinal transection in C5/C6 and monosynaptic excitation from the ipsilateral lateral reticular nucleus. The pyramidal disynaptic excitation was facilitated by a conditioning volley evoked from the contralateral nucleus ruber, which suggests convergence of cortico- and rubrospinal fibres on the intercalated neurones. It is proposed that laminae VII and VIII neurones receive a collateral input from the same excitatory C3–C4 propriospinal neurones which project to motoneurones and/or Ia inhibitory interneurones. Reconstruction of HRP-stained lamina VII and VIII neurones revealed ipsi- and contralateral ascending and/or descending axonal projections and termination in laminae VII and VIII in the forelimb segments.

Collateralization and termination of single C3-C4 propriospinal neurones (PNs) have been studied in the C6-Th1 segments of the cat using two methods: threshold mapping for antidromic activation of C3-C4 PNs and intra-axonal injection of horseradish peroxidase. Low threshold points for antidromic activation of C3-C4 PNs were found in the region of different motor nuclei in lamina IX both at one level and at different segmental levels, in all parts of lamina VII, in the lateral part of lamina VI and in the dorsal and ventral parts of lamina VIII. Collaterals were found from C6 to Th1. A marked decrease of conduction velocity of the stem axon occurred in the caudal region of termination, while it was almost constant in the rostral region of termination. HRP was injected iontophoretically in C6-Th1 into stem axons of neurones, which were activated antidromically from the ventral part of the lateral funiculus in C5/C6, from the lateral reticular nucleus (LRN) and monosynaptically from the corticospinal fibres (stimulated in the contralateral pyramid) which were transected in C5/C6. Reconstruction of successfully stained stem axons, revealed collaterals with terminals on presumed motoneurones in different parts of lamina IX and on interneurones in laminae IV-VIII. These findings confirm previous results which showed monosynaptic projections from C3-C4 PNs to forelimb motoneurones and Ia inhibitory interneurones. With respect to termination in the region of the motoneurones in lamina IX and in the region of Ia inhibitory interneurones in lamina VII, three patterns were found: 1) termination mainly in lamina IX (n = 1) 2) termination in laminae IX and VII (n = 15) and 3) termination mainly in lamina VII (n = 2). However, in some cases the same stem axon gave off collaterals which terminated either on motoneurones in lamina IX or on presumed Ia inhibitory interneurones in lamina VII. Furthermore, when the stem axons had collaterals which terminated in different motor nuclei only some of these collaterals had additional terminations on presumed Ia inhibitory interneurones. This result suggest that C3-C4 PNs do not follow a strict Ia pattern of reciprocal innervation. It is tentatively proposed that the difference of innervation may be related to the type of multi-joint movement, such as target-reaching with the forelimb, which has been shown to be controlled by the C3-C4 PNs. Termination in laminae VI, VIII and different parts of lamina VII indicates that C3-C4 PNs also project to other types of neurones than motoneurones and Ia inhibitory interneurones.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of octapeptide angiotensin II (AII) were tested on cortical neurons of rat's cerebellum by means of microiontophoresis. It was observed that AII consistently depressed spontaneous firing of Purkinje cell, whereas other unidentified neurons were unaffected. When tested against responses of Purkinje cell to depressant putative neurotransmitters, namely, GABA, glycine, taurine, 5-hydroxytryptamine and noradrenaline, it was observed that AII specifically enhanced depressant action of GABA, while the responses to other substances were unaffected. Both AII-induced depression of cell firing and the AII-induced enhancement of GABA depression were antagonized by a specific GABA antagonist, bicuculline methochloride. We therefore suggest that AII exerts an inhibitory action on Purkinje cells through its modulatory action on bicuculline-sensitive GABA receptors.

The food-taking movement by which a cat uses its forepaw to take a piece of food and bring it to its mouth normally depends on the cortico- (CS) and rubrospinal (RS) tracts and disappears when they are transected in C5; a slow reappearance over months is due to bulbospinal (BS) take-over. After complete CS transection but minimal RS transection, food-taking remains. If, one month later, the RS tract is completely transected, food-taking is not abolished as it is when transection is made in one session. It is permanently abolished after a third transection of the ventral quadrant in C2. It is suggested that the food-taking remaining after the first lesion is due to combined RS and BS activity and that the RS tract induces the BS neurones to contribute to the extent that they can take over when the RS tract is completely transected.

Complete transection of the pyramid just rostral to the crossing gave defects in forelimb target-reaching and food-taking tested with retrieval of food from a cylinder. The most marked symptoms were dysmetria, dyscoordination of movement and almost total loss of the food-taking movement. Gradual recovery occurred, but even after 3-4 months the food-taking movement was deficient. The symptoms were less severe than those previously found after a high pyramidotomy but much more pronounced than those observed after complete transection of the corticospinal tract in the spinal cord. The motor defects after a low pyramidotomy closely resemble those found after a high dorsal column transection. It is tentatively proposed that the motor defects after low pyramidotomy are largely due to transection of corticocuneate fibers which regulate the feedback pathway from forelimb afferents to the motor cortex.

Background In order to gain insight into neuroprotective effects of ECa 233, a standardized extract of Centella asiatica, previously demonstrated in animal models of memory impairment induced by transient global ischemia or intracerebroventricular injection of β-amyloid, the effect of ECa 233 on neurite outgrowth of human IMR-32 neuroblastoma cell line was investigated. Methods Cells were seeded and incubated with various concentrations of ECa 233. Morphometric analysis was carried out by a measurement of the longest neurite growth of cells at 24 and 48 h. Contributing signaling pathways possibly involved were subsequently elucidated by western blot analysis. Results While ECa 233 had only limited effects on cell viability, it significantly enhanced neurite outgrowth of IMR-32 cells at the concentrations of 1–100 μg/ml. Western blot analysis revealed that ECa 233 significantly upregulated the level of activated ERK1/2 and Akt of the treated cells suggesting their involvement in the neuritogenic effect observed, which was subsequently verified by the finding that an addition of their respective inhibitors could reverse the effect of ECa 233 on these cells. Conclusions The present study clearly demonstrated neurite outgrowth promoting activity of ECa 233. ERK1/2 and Akt signaling pathways seemed to account for the neurotrophic effect observed. In conjunction with in vivo neuroprotective effect of ECa 233 previously reported, the results obtained support further development of ECa 233 for clinical use in neuronal injury or neurodegenerative diseases.