Reduced bone mineral density and radial bone growth in young rabbits treated with dexamethasone eye drops

OBJECTIVE: To investigate the effect of dexamethasone eye drops on bone metabolism in newborn rabbits. METHODS: Thirty-four 3-week-old rabbits had unilateral clear lens extraction and were randomized into three groups. Postoperatively, group 1 received high-dose and group 2 low-dose dexamethasone eye drops (average doses 0.27 and 0.10 mg/kg body weight/day, respectively). These rabbits also received a postoperative subconjunctival injection of betamethasone. Group 3 (control) received vehicle eye drops only. After 8 weeks of treatment, all animals were killed and the left femurs were isolated and subjected to peripheral quantitative computerized tomography (pQCT) and dual X-ray absorptiometry (DXA) analyses. RESULTS: DXA showed that rabbits treated with either a high or low dose of dexamethasone eye drops had significantly reduced areal bone mineral density (BMD), area and total bone mineral content (BMC) of the femur. Measurements with pQCT demonstrated a dose-dependent reduction in cortical BMC, cortical volumetric BMD and cortical area. These effects were associated with an inhibition of radial femur growth, cortical thickness and periosteal and endosteal circumferences. CONCLUSION: Dexamethasone eye drops have systemic effects affecting several bone parameters in young rabbits. Any long-term systemic effects of ocular glucocorticoids need to be further studied.     

St. John's wort (Hypericum perforatum L.) and kindling epilepsy in rabbit.

Effects of different extracts of Hypericum perforatum L. on the kindling epileptic discharges were analyzed. The experiment was carried out on Chinchilla rabbits with chronically implanted electrodes in cortical structures and hippocampus. In our study we used water, n-butanol and ether fractions (mass concentrations 0.1 g/ml) of crude ethanol extract of Hypericum perforatum. The particular extracts were given intramuscularly in single dose of 1 ml/kg BW. The bioelectric activity was registered before and after applications of each extracts. The obtained results show that the effect depends on the constituents present in particular fractions. The repression of epileptic activity was in correlation with the polarity of plant constituents. Most polar constituents that remained in water fraction exerted highest antiepileptic activity in all (100%) animals tested. Substances present in butanol fraction repressed the epileptic manifestations in 40% of animals with kindling epilepsy, whereas lipid-soluble constituents in ether fraction potentated the epileptic activity.     

Long-term treatment with lithium salts and cerebral electric activity. Experimental research

An eeg study was carried out in rabbits to investigate the neurophysiological effects of chronic lithium clorure treatment. The Monnier and Gangloff's stereotaxic method was used for recording cortical and deep structure activity. Lithium clorure was administered i.p. at doses of 20 mg/Kg/die for 15-22 days (mean plasmatic levels: 0.04 mEq/l). The eeg changes consisted in synchronization of the cortical activity, slowing of the deep structure activity and increase of CAD spiking. The most interesting finding was the appearance of peculiar periodic spikes in the CAD and subcortical structures. A similar pattern has been previously described by us in rabbits treated with repeated ECT.     

5-羟色胺对电针抑制青霉素痫样放电的作用

本工作研究电针抑制青霉素所致大脑皮层痫样放电中5-羟色胺的作用。大鼠腹腔注射对氯苯丙氨酸,注射后第4天麻醉开颅,皮层施加青霉素引起痫样放电,并记录逆向刺激锥体央所引起的皮层回返抑制电位(SN)。在注药后动物,电针制痫作用明显减弱,痫波幅度及频率减小缓慢,SN 的恢复也较对照缓慢。电解损毁中缝背核后电针制痫作用亦减弱,痫波发作时程显著延长。电刺激中缝背核可促进痫波振幅及频率的衰减,发作时程缩短。电刺激中脑导水中管周围 灰质有遏制痫波的作用,但在注射对氯苯丙氨酸后此作用亦趋减弱。以上结果表明,在电针制痫中5-HT及5-HT能神经元集中的中缝背核起重要作用。     

The effects of thyrotropin-releasing hormone on cyclic AMP accumulation in rabbit cerebral cortical tissue in the presence and absence of CNS depressants

The $\text{in vitro}$ effects of thyrotropin-releasing hormone on cAMP accumulation in cortical brain slices from rabbits is reported. Incubation of cortical tissue at three concentrations of thyrotropin-releasing hormone (1,2,5nM) had no discernible effects on baseline cAMP levels. When cortical tissue was incubated in the presence of pentobarbital (.5mM) or if cortical tissue was taken from animals pretreated with α-methyl-p-tyrosine (α-MPT), the baseline cAMP accumulation was depressed. This depression could be eliminated by the addition of TRH to the incubation media. Where cortical tissue from atropine-pretreated animals was used or when atropine was added to the incubation media, there was an increase in baseline cAMP accumulation which was unaffected by addition of TRH. These results show that TRH can modify cAMP accumulation in mammalian cortical brain tissue but this ability may only become evident in situations where normal cAMP concentration has been depressed.     

Memory Consolidation in the Cerebellar Cortex

Several forms of learning, including classical conditioning of the eyeblink, depend upon the cerebellum. In examining mechanisms of eyeblink conditioning in rabbits, reversible inactivations of the control circuitry have begun to dissociate aspects of cerebellar cortical and nuclear function in memory consolidation. It was previously shown that post-training cerebellar cortical, but not nuclear, inactivations with the GABA_A agonist muscimol prevented consolidation but these findings left open the question as to how final memory storage was partitioned across cortical and nuclear levels. Memory consolidation might be essentially cortical and directly disturbed by actions of the muscimol, or it might be nuclear, and sensitive to the raised excitability of the nuclear neurons following the loss of cortical inhibition. To resolve this question, we simultaneously inactivated cerebellar cortical lobule HVI and the anterior interpositus nucleus of rabbits during the post-training period, so protecting the nuclei from disinhibitory effects of cortical inactivation. Consolidation was impaired by these simultaneous inactivations. Because direct application of muscimol to the nuclei alone has no impact upon consolidation, we can conclude that post-training, consolidation processes and memory storage for eyeblink conditioning have critical cerebellar cortical components. The findings are consistent with a recent model that suggests the distribution of learning-related plasticity across cortical and nuclear levels is task-dependent. There can be transfer to nuclear or brainstem levels for control of high-frequency responses but learning with lower frequency response components, such as in eyeblink conditioning, remains mainly dependent upon cortical memory storage.     

电针对青霉素所致大脑皮层痫样放电的抑制作用

青霉素置于大鼠大脑皮层感觉运动区所诱发的皮层痫样放电,可被一些“穴位”电针所抑制,表现为放电频率、振幅及时程之减少。青霉素使逆向刺激锥体束所产生的感觉运动皮层表面负波减小,而电针则促进其恢复。因此电针制痫与它促进回返抑制的恢复有关。将微量纳洛酮注入腹腔、脑室及中脑导水管周围灰质、伏隔核均能翻转电针的作用。将纳洛酮直接注入放置青霉素处的皮层感觉运动区,针效亦被阻断。这表明电针制痛中有内啡肽参与。电刺激中脑导水管周围灰质及伏隔核有显著制痫作用。     

Neuropeptides and cerebral electric activity in rabbits

The effects of some neuropeptides infused into the cerebral ventricles on the spontaneous cerebral electric activity were studied in unanasthetized rabbits. The following peptides were investigated: physalaemin, caerulein, bombesin, litorin (supplied by Farmitalia). The rabbits were prepared according to Monnier and Gangloff's [10] method in order to record the spontaneous cortical activity. Each of these substances affects the electroencephalographic (EEG) records in a specific and dose-related way. Bombesin induces a biphasic pattern (synchronization followed by a partial activation), litorin is partially activating and physalaemin brings about a marked desynchronization. In spite of the marked structural analogy between bombesin and litorin, their EEG effects differ.     

Effects of the calcium antagonist NB-818 on cerebral blood flow

The effects of intravenous injection of NB-818, isopropyl methyl 2-carbamoyloxymethyl-6-methyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine-3,5- dicarboxylate, on regional cerebral blood flow were studied in rabbits and Rhesus monkeys, using the hydrogen clearance technique. The above effects were compared with those of nicardipine and nimodipine. In rabbits, NB-818 (10 micrograms/kg i.v.) increased both cerebral cortical blood flow (rCBF) and cerebellar cortical blood flow by about 80% of the predrug level with a moderate decrease in mean arterial blood pressure, and no increase in skeletal muscle blood flow. The increase in cerebral blood flow with NB-818 was as great as that with nicardipine or nimodipine. In Rhesus monkeys, NB-818 (10-20 micrograms/kg i.v.) increased rCBF by about 30% of the predrug level, and its effect continued 30-60 min after dosing. The increase in rCBF with NB-818 was greater than that with nicardipine. The results from the present study indicate that NB-818 predominantly increases rCBF with a concomitant moderate hypotension, and its action is greater than that of nicardipine or nimodipine.     

Effect of acupuncture on the activity of experimental epileptogenic foci in the hippocampus of rabbits

Experiments were performed on rabbits with electrochemotrodes implanted into the left and right dorsal hippocamp. The evidence was obtained for the first time as to the marked inhibitory effect of acupuncture on epileptogenic foci created by penicillin microinjections into the hippocamp. The most effective was stimulation of the Min-Men point. The antiepileptic effect was potentiated on combined stimulation of the Min-Men and Yao-Yan-Guan points. The efficacy of the procedure was significantly decreased on stimulation of the points of another acupunctural canal. The epileptiform activity was potentiated by affecting the knowingly inactive points. The antiepileptic effect of acupuncture was significantly reduced with an increase in the number of acupunctures. This might be connected with the development of tolerance to enkephalins by which the effect of acupuncture is most likely mediated.     

Strain differences in rabbit adrenocortical structure and morphological evidence of corticomedullary communication

Interstrain differences in the structure of the mouse and rat adrenal cortex are well known, but related data on rabbits are not available. This study was planned to demonstrate possible strain differences in rabbit adrenal morphology and morphological evidence of a communication between cortex and medulla. For this purpose, the zonation of the adrenal cortex of intact mature male and female rabbits of different strains (New Zealand, Chinchilla and California) were compared using morphometry and the corticomedullary junction was evaluated for close relationship. Marked intersex and interstrain differences were found in the adrenocortical zonation. Female rabbits had larger adrenocortical zones than corresponding males. The rabbits of Chinchilla and California strains had the largest cortical sizes. This difference depended largely upon the higher thickness of the zona fasciculata. Whereas, there were no significant strain differences in the thickness of zona glomerulosa and zona reticularis. Furthermore, examination of corticomedullary junction showed that cortex and medulla were interwoven. Single and small accumulations of cortical cells were spread throughout the medulla. Our morphological data showed the presence of significant interstrain differences in the adrenocortical zonation in the rabbits and provide evidence for a possible paracrine interaction between medullary and cortical cells.     

Phase relationships of cerebral cortex potentials in the rabbit during the execution of motor responses

EEG waves phase relations in the sensorimotor and visual cortical areas were studied in 12 rabbits before and during a motor reaction in response to light stimulation. Phase relations in the background activity were characterized by a considerable dispersion (from 26 to 45 degrees). Light stimulation increased the quantity of synphasic EEG oscillations in adjacent cortical points and stabilized the phase shift between EEG waves in the sensorimotor and visual cortical areas. Motor reactions of rabbits to light occurred when theta-rhythm with the most constant phase shift was observed in the EEG of these areas.     

Modulation of V1-receptor-mediated renal vasoconstriction by epoxyeicosatrienoic acids

This study examined the effects of renal arterial infusion of a selective cytochrome P-450 epoxygenase inhibitor, N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide (MS-PPOH; 2 mg/kg plus 1.5 mg.kg(-1).h(-1)), on renal hemodynamic responses to infusions of [Phe(2),Ile(3),Orn(8)]vasopressin and ANG II into the renal artery of anesthetized rabbits. MS-PPOH did not affect basal renal blood flow (RBF) or cortical or medullary blood flow measured by laser-Doppler flowmetry (CLDF/MLDF). In vehicle-treated rabbits, [Phe(2),Ile(3),Orn(8)]vasopressin (30 ng.kg(-1).min(-1)) reduced MLDF by 62 +/- 7% but CLDF and RBF were unaltered. In MS-PPOH-treated rabbits, RBF and CLDF fell by 51 +/- 8 and 59 +/- 13%, respectively, when [Phe(2),Ile(3),Orn(8)]vasopressin was infused. MS-PPOH had no significant effects on the MLDF response to [Phe(2),Ile(3),Orn(8)]vasopressin (43 +/- 9% reduction). ANG II (20 ng.kg(-1).min(-1)) reduced RBF by 45 +/- 10% and CLDF by 41 +/- 14%, but MLDF was not significantly altered. MS-PPOH did not affect blood flow responses to ANG II. Formation of epoxyeicosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DiHETEs) was 49% lower in homogenates prepared from the renal cortex of MS-PPOH-treated rabbits than from vehicle-treated rabbits. MS-PPOH had no effect on the renal formation of 20-hydroxyeicosatetraenoic acid (20-HETE). Incubation of renal cortical homogenates from untreated rabbits with [Phe(2),Ile(3),Orn(8)]vasopressin (0.2-20 ng/ml) did not affect formation of EETs, DiHETEs, or 20-HETE. These results do not support a role for de novo EET synthesis in modulating renal hemodynamic responses to ANG II. However, EETs appear to selectively oppose V(1)-receptor-mediated vasoconstriction in the renal cortex but not in the medullary circulation and contribute to the relative insensitivity of cortical blood flow to V(1)-receptor activation [corrected].     

The effect of low frequency peripheral stimulation on the tail-flick reflex and evoked cortical potentials in the rabbit

The effects of low frequency peripheral electrical stimulation of innocuous intensity (LES) on the tail-flick latency and the amplitude of the late component of the cortical potentials evoked by single electrical stimuli (20-40 ms latency) were studied in 59 awake and restrained rabbits. Increase of the tail-flick latency and profound decrease of the amplitude of the late positive component of evoked cortical potentials was observed in 50 animals. Five animals of this group and five animals from a group of 9, resistant to electrostimulation, were tested to the analgesic effects of morphine using the same criteria. Positive effects were found in the former but not in the latter group. Naloxone (0.1 mg/kg) profoundly decreased the effects of LES which suggests that an opioid mechanism is involved in the action of conditioning electrostimulation. Pretreatment of the animals with serotonin depletor p-CPA resulted in partial blockade of the effects of LES. The blockade was removed by administration of serotonin precursor 5-HTP. This is in agreement with the hypothesis that the opioid effects are partially exerted through serotoninergic descending pathways.     

Modulation of the neuronal activity and evoked potentials of the cerebral cortex by stimulation of the dorsal hippocampus]

In experiments on alert rabbits high frequency stimulation of the CA1 field of the dorsal hippocampus reduced the peak latency of the main negative component of the evoked potential (EP) to a light flash in the sensorimotor and occipital tests areas of the cerebral cortex. A single stimulation of the same part of the hippocampus resulted in a gradually developing facilitation of secondary negativity of the EP 5th component, predominantly in the sensorimotor cortex. Investigation of neuronal responses in the same cortical areas to a stimulation of the CA1 field with different parameters has shown that the effects of EP modulation are due to dynamic reorganizations of cortical neuronal activity.     

Activity of rabbit's neocortical and hippocampal neurons in orienting-exploratory behavior and freezing

By plotting autocorrelation histograms, the character of impulsation of neurons in bilateral derivations from cortical visual and somatosensory areas and hippocampal field CA1 was studied in rabbits during free behavior under the influences of emotional stimuli. During active orienting-exploratory reaction of rabbits, most cortical and hippocampal neurons manifested bursting discharges and theta-frequency oscillation (predominantly 4-5 Hz in cortex and 4-5, 6-7 in hyppocampus). During freezing, as compared with active locomotor reaction, the number of neurons with equiprobabilistic discharges increased; in impulsation of neurons with periodicity, the intensity of delta-frequency oscillation increased (predominantly 2-4 Hz) but theta-frequency oscillation decreased. The number of neurons with delta-frequency oscillation during freezing was greater then in calmly sitting rabbits.     

The modulation of sensory transmission through the medullary dorsal horn during cortically driven mastication

During mastication, reflexes are modulated and sensory transmission is altered in interneurons and ascending pathways of the rostral trigeminal sensory complex. The current experiment examines the modulation of sensory transmission through the most caudal part of the trigeminal sensory system, the medullary dorsal horn, during fictive mastication produced by cortical stimulation. Extracellular single unit activity was recorded from the medullary dorsal horn, and multiple unit activity was recorded from the trigeminal motor nucleus in anesthetized, paralyzed rabbits. The masticatory area of sensorimotor cortex was stimulated to produce rhythmic activity in the trigeminal motor nucleus (fictive mastication). Activity in the dorsal horn was compared in the presence and absence of cortical stimulation. Fifty-two percent of neurons classified as low threshold and 83% of neurons receiving noxious inputs were influenced by cortical stimulation. The cortical effects were mainly inhibitory, but 21% of wide dynamic range and 6% of low threshold cells were excited by cortical stimulation. The modulation produced by cortical stimulation, whether inhibitory or excitatory, was not phasically related to the masticatory cycle. It is likely that, when masticatory movements are commanded by the sensorimotor cortex, the program includes tonic changes in sensory transmission through the medullary dorsal horn.     

Influence of clonazepam on cortical epileptogenic foci in the rat

The antiepileptic action of clonazepam was studied on epileptogenic foci induced by penicillin in sensorimotor cortex in acute experiments in rats. Clonazepam (1 mg/kg intraperitoneally) only moderately decreased the frequency of interictal discharges of single cortical focus and delayed the propagation of discharges into the ipsilateral occipital region. On the contrary, clonazepam failed to influence the callosal projection of interictal discharges in single unilateral as well as in two symmetrical foci. Spontaneous transition of interictal discharges into ictal phases regularly seen when two symmetrical foci were formed was only delayed but not blocked by clonazepam. It may be concluded that clonazepam exhibits only a weak anticonvulsant action against cortical foci and against secondary generalization of epileptic activity.     

The effect of acetylcholine on shifts in the spatial synchronization of the cortical potentials in the rabbit evoked by the reversible interruption of the mammillary body connections

To study the role of cholinergic transmitter system in the maintenance of sychronizing limbic influences, the dynamics of the spatial distribution of the changes of cross-correlation coefficients of rabbits EEG led by 24 electrodes, was estimated at application of acetylcholine solution to the visual cortical area in combination with anode polarization of mammillary bodies. Acetylcholine, which separate effect was connected with a restricted increase of the spatial synchronization of potentials, completely eliminated the effects of isolated polarization expressed in a significant decrease of a half of calculated correlation coefficients between EEGs of the visual and motor cortical areas. Nonspecific cholinergic synchronizing system is supposed to exist which is active under the conditions of the mammillo-thalamo-cortical connections being intact.     

The vestibular cortical projection during spinal decompensation

The removal of spinal afferents in rabbits submitted to unilateral lesion of the labyrinth and fully compensated greatly modified the field potentials as well as the single unit responses recorded from the cortical vestibular area during stimulation of the intact eighth nerve. In particular, an increase of contralateral and a decrease of ipsilateral potentials were observed. These asymmetrical responses indicate that the influence of the spinal cord in compensating the effects of unilateral lesion of the labyrinth is directed to balance not only the electrical activity of the brain-stem structures, but also that of the cerebral cortex. It appears, therefore, that spinal signals intervene not only in the compensation of vestibulospinal and vestibulo-oculomotor functions but also of cortical functions, such as that related to vestibular sensation.