Dynamics of the activity of the postural asymmetry factor after unilateral damage to the motor area of the cortex

The authors studied the time-course of functional rearrangements of the segmental apparatus after unilateral injury of the rat motor cortex. It was found that one day after injury the postural asymmetry of the hind limbs was fixed by the lumbal region of the spinal cord. This functional state of the segmental apparatus lasted 10 days after injury in the presence of the maximal activity of postural asymmetry factor (PAF) in the CSF and increasing activity of the factor in the brain tissue. Recovery of the segmental apparatus to symmetrical function by the end of the third week following injury was accompanied by PAF inactivation.     

Dynamics of the activities of postural asymmetry factors and of the recovery of motor function in damage to the neocortex of the left and right hemispheres

The role of postural asymmetry factors in the recovery of motor function after unilateral cortical lesions was investigated. The differences in the time-course of motor reactions recovery after left- and right-sided cortical damage was found. A more effective compensation of motor defects in animals with left-sided damage was accompanied by stable activity of postural asymmetry factors. The reported results indicate an important role of postural asymmetry factors in the early compensatory intra-central rearrangements.     

Recovery of baroreflex control of renal sympathetic nerve activity after spinal lesions in the rat

Spinal cord injury (SCI) has serious long-term consequences on sympathetic cardiovascular regulation. Orthostatic intolerance results from insufficient baroreflex regulation (BR) of sympathetic outflow to maintain proper blood pressure upon postural changes. Autonomic dysreflexia occurs due to insufficient inhibition of spinal sources of sympathetic activity. Both of these conditions result from the inability to control sympathetic activity caudal to SCI. It is well established that limited motor ability recovers after incomplete SCI. Therefore, the goal of this study was to determine whether recovery of BR occurs after chronic, left thoracic spinal cord hemisection at either T(3) or T(8). Baroreflex tests were performed in rats by measuring the reflex response of left (ipsilateral) renal sympathetic nerve activity to decreases and increases in arterial pressure produced by ramped infusions of sodium nitroprusside and phenylephrine, respectively. One week after a T(3) left hemisection, BR function was modestly impaired. However, 8 wk after a T(3) left hemisection, BR function was normal. One week after a T(8) left hemisection, BR function was significantly impaired, and 8 wk after a T(8) left hemisection, BR function was significantly improved. These results indicate that BR of renal sympathetic nerve activity in rats may partially recover after spinal cord hemisections, becoming normal by 8 wk after a T(3) lesion, but not after a T(8) lesion. The nature of the spinal cord and/or brain stem reorganization that mediates this recovery remains to be determined.     

Formation of postural asymmetry in rat hindlimbs during colchicine-induced unilateral blockade of axonal transport in cortico-lumbar projections

The possibility of the formation of spinal cord functional asymmetry by the blockade of axonal transport in corticolumbar projections with colchicine was investigated. To identify the blockade of axonal transport, the method of retrograde transport of horseradish peroxidase was used. The blockade of axonal transport led to the formation of the asymmetric functional status of the spinal cord, manifesting in postural asymmetry of the hind limbs and characteristic changes in the pattern of bioelectrical activity of the flexor muscles. An endogenous factor inducing postural asymmetry in intact recipients was detected in the cerebrospinal fluid of colchicine treated animals. Based on the experimental data the conclusion is drawn that interruption of normal axonal transport attests to the destruction of central neurons.     

Characteristics of the development of postural asymmetry in rats as affected by the opioids met-enkephalin and the kappa-agonist bremazocine

It has been found that bremazocine and met-enkephalin induce postural asymmetry in spinal rats under subarachnoidal and intravenous administration. Intravenous administration of bremazocine to intact animals--even if after it (an hour later) their spinal cord is sectioned--produces no asymmetry, i. e. the spinal cord section is necessary for asymmetry development. The magnitude of postural asymmetry and the side of limb flexion are not constant for each animal, but they change in time. Though, on the average, the percent of asymmetric animals and the ratio of left and right flexions in each group of animals are practically constant. When the spinal cord is sectioned at the T1-T4 level, the bremazocine and metenkephalin induce mainly the right-leg flexion: when the section is made at the T5-T9 level, the left-leg is bent, i. e. the flexion side depends on the level of the section. It is suggested that the ability of opioids to induce postural asymmetry is based on lateralization of opioid receptors in the rat spinal cord.     

Met-enkephalin-induced release into the blood of a factor causing postural asymmetry

Met- and Leu-enkephalin applied subarachnoidally into the rostral portion of a transected spinal cord (at the T6-T7 level) induce postural asymmetry of the hind limbs in rats, Met-enkephalin being predominantly responsible for the flexion of the right, and Leu-enkephalin of the left, hind leg. The blood serum of rats injected with Met-enkephalin contains a factor which, when administered subarachnoidally into the caudal portion of the transected spinal cord, is capable of inducing the hind limb postural asymmetry--predominantly, with the right leg flexion. This factor is inactivated by papain and differs from Met- and Leu-enkephalin in chromatographic properties. Apparently, Met-enkephalin induces the release of a peptide factor into the blood, from the brain or organs innervated by the neurons lying above the cut. It is then carried with the blood to the hind limbs and effects the hind limb postural asymmetry.     

Identification of the spinal pathways involved in the recovery of baroreflex control after spinal lesion in the rat using pseudorabies virus

Neurons in the rostroventrolateral medulla (RVLM) mediate baroreflex regulation (BR) of spinal sympathetic preganglionic neurons. Previously, our laboratory has shown that recovery of BR occurs in the rat after spinal hemisection. (Zahner MR, Kulikowicz E, and Schramm LP. Am J Physiol Regul Integr Comp Physiol 301: R1584-R1590, 2011). The goal of these experiments was to determine whether the observed recovery of BR is mediated by the reorganization of ipsilateral pathways or by compensation by spared contralateral pathways. To determine this, we infected the left kidney in rats with the retrograde transynaptic tracer, pseudorabies virus (PRV), either 1 or 8 wk after left spinal hemisection at either T(3) or T(8), or after a sham lesion. In sham-lesioned rats, PRV infection of RVLM neurons was bilateral. In all rats with a left hemisection, regardless of the location of the lesion (T(3) or T(8)) or postlesion recovery time (1 or 8 wk), PRV infection of left RVLM neurons was significantly reduced compared with sham-lesioned rats (P < 0.05). In a separate group of rats, we performed BR tests by measuring responses of left renal sympathetic nerve activity to pharmacologically induced decreases and increases in arterial pressure. In rats with T(8) left hemisection and 8-wk recovery, BR was robust, and acute right upper thoracic hemisection abolished all BR of left renal sympathetic nerve activity. Collectively, these data suggest that the recovery of BR is not mediated by reorganization of ipsilateral bulbospinal connections, but instead by improved efficacy of existing contralateral pathways.     

Characteristic Features of Disorders of the Upright Posture in Patients with Poststroke Hemipareses

Characteristic features of upright posture maintenance and mechanisms of postural disorders in poststroke hemiparetic patients were studied using a bilateral force platform. The following features of postural disorders were revealed in the patients tested: an increase in the velocity and amplitude of the center-of-pressure (CP) sway as compared to in healthy subjects, an absolute decrease in the half-cycles of the CP sway, asymmetry of weight bearing by both feet, and a shift of the center of pressure of an affected foot towards the toe. The disturbance of stability of the vertical posture in such patients is to a greater extent associated with weight-bearing asymmetry. It was shown that the character of the CP sway is mainly determined by a disorder of the sensory motor control, whereas damage to the efferent pathways is responsible for the postural asymmetry. Increase in the muscle tone restricts the sway amplitude. Thus, several forms of postural instability are characteristic of hemiparetic patients. Predominantly sensory, motor, or tonic disorders are responsible for these disturbances of stability.     

Methoxychlor-Induced Alterations in the Histological Expression of Angiogenic Factors in Pituitary and Uterus

Within the reproductive system, oestrogenic stimulation of uterine and pituitary tissue typically causes a proliferative response accompanied by an angiogenic induction of new blood vessels from existing ones, thereby providing nutrients and oxygen to the growing tissue. The pro-oestrogenic pesticide methoxychlor (MXC), however, has shown a differential effect on proliferative activity. An increase in uterine growth is present, while the pituitary undergoes a decrease in size, even though the effect is accompanied by a characteristic oestrogen-induced elevation in pituitary prolactin concentration. The focus of the current study was whether the observed differences in tissue growth between uterus and pituitary in response to MXC administration were paralleled by a corresponding disparity in the expression of those growth factors (members of the vascular endothelial growth factor (VEGF) and angiopoietin families and their receptors) that are involved in the angiogenic cascade. Ovariectomized adult Sprague-Dawley female rats were administered MXC (0-200 mg/kg, oral) for 1 or 3 weeks. Immunohistochemical staining of uteri and pituitaries was performed under strictly controlled conditions for VEGF and its receptor VEGFR2, Angiopoietin-1 (Ang1) and angiopoietin-2 and their tyrosine kinase receptor Tie2, and platelet endothelial adhesion factor (as an index of vascularity). Image acquisition and densitometric assessments of staining intensity were conducted under blind conditions. The results showed uterine MXC-induced increases in the expression of VEGFR2 and Ang1, changes consistent with a normal proliferative response to oestrogenic stimulation. For VEGF, staining tended to be most pronounced in the stromal region, although there did not appear to be a progressive increase with dose. VEGFR2 expression showed significant dose-related trends in luminal and glandular epithelia by 1 week. Similar effects at 1 week were evident for Ang1 in glandular epithelium. In the anterior pituitary, a dose-related increase in VEGF was present for the 1 and 3 week treatments, and the number of pituitary vessels per unit area was also increased after 3 weeks. The effects indicate that even though the insecticide has not been found to cause an augmentation in pituitary growth, a dose-related rise in the expression of at least one principal angiogenic factor is present that may be associated with an increase in vascular density.     

Immunoreactive delta sleep-inducing peptide in the rat hypothalamus, pituitary and adrenal gland: effects of adrenalectomy

Immunoreactive (IR) delta sleep-inducing peptide (DSIP) was examined by immunocytochemistry in the rat pituitary and adrenal gland and found to be colocalized with IR thyroid-stimulating hormone in the pituitary and with noradrenaline in the adrenal medulla. IR-DSIP was also detectable in nerve fibers in the posterior pituitary. By radioimmunoassay, IR-DSIP was quantified in plasma and tissue extracts after uni- or bilateral adrenalectomy. Significantly elevated plasma levels of IR-DSIP were measured 5 days after bilateral adrenalectomy (p less than 0.001). IR-DSIP was increased (p less than 0.05) in pituitary extracts from bilaterally adrenalectomized rats after 5 days, but not after 14 or 28 days. Sham- and unoperated animals did not significantly differ in plasma or tissue concentration of IR-DSIP. High-performance liquid chromatography of C18 SEP-PAK purified hypothalamus extracts revealed a single peak of IR-DSIP material of lower hydrophobicity than synthetic DSIP. The elevated concentration of IR-DSIP in the rat pituitary and plasma after bilateral adrenalectomy is consistent with the previously suggested role of DSIP to influence the activity of the hypothalamic-pituitary-adrenal axis.     

Changes of postural tonus produced by unilateral deafferentation of the musculature of the neck in pigeons

In intact or decerebrate pigeons, unilateral functional deafferentation of the dorsal neck muscles of one side produced a postural asymmetry, characterized by an increase in flexor tonus of the ipsilateral wing and leg and an increase in extensor tonus of the contralateral limbs. This postural asymmetry was just opposite in sign to that described recently in cats, where unilateral section of the cervical dorsal roots C1-C3 produced ipsilateral hypertonia and contralateral hypotonia of the limb extensors. The striking increase in flexor tonus of the wing following deafferentation of the ipsilateral neck extensors contrasts with the decrease in flexor tonus of the wing which occurs after deafferentation of the ipsilateral leg extensors. It appears, therefore, that the proprioceptive input from the neck and that from the leg extensors exert an antagonistic influence on the flexor tonus of the ipsilateral wing.     

Inhibition of vestibulospinal reflexes during the episodes of postural atonia induced by unilateral lesion of the locus coeruleus in the decerebrate cat

1. The spontaneous EMG activity of the forelimb extensor triceps brachii of both sides as well as their responses to roll tilt of the animal at 0.15 Hz, +/- 10 degrees leading to sinusoidal stimulation of labyrinth receptors were tested in precollicular decerebrate cats, before and after unilateral electrolytic lesion of the locus coeruleus (LC). 2. Lesion of the LC of one side decreased the tonic contraction of the ipsilateral limb extensors, but greatly increased the amplitude of modulation and the response gain of the corresponding triceps brachii to animal tilt; however, no change in the phase angle of the responses was observed. A slight increase in the response gain affected also the contralateral triceps brachii. 3. The postural asymmetry described above was followed from time to time by short-lasting episodes of postural atonia, which affected not only the ipsilateral but also the contralateral limb extensors. These episodes were also associated with a suppression of the EMG responses of the triceps brachii of both sides to sinusoidal stimulation of labyrinth receptors. 4. The episodes of postural atonia which appeared after unilateral lesion of the LC were not associated with rapid eye movements; however, the slow horizontal eye movements, which may occur in normal decerebrate animals, increased in amplitude throughout these episodes. Both the postural atonia as well as the related suppression of the vestibulospinal reflexes, which lasted for 5-10 min, disappeared either spontaneously or following acoustic or somatosensory stimulations. 5. Histological controls indicated that unilateral lesions limited to the caudal part of the LC produced only a permanent decrease in postural activity of the ipsilateral limbs, associated with an increase in gain of the vestibulospinal reflex. However, in order to elicit episodes of bilateral postural atonia associated with the suppression of the vestibulospinal reflexes it was necessary to extend the lesion to more rostral aspects of the LC. 6. Since the effects described above were similar to those elicited in decerebrate cats by local injection of cholinergic agonists into the dorsal part of the pontine reticular formation, we postulated that the postural atonia as well as the related suppression of the vestibulospinal reflexes was due to transient release from LC inhibition of these dorsal pontine reticular structures, which might in turn excite the medullary reticulospinal neurons, thus leading to inhibition of the extensor motoneurons.(ABSTRACT TRUNCATED AT 400 WORDS)     

The effects of lesioning both the superior colliculus and the substantia nigra of cats on turning behavior

In twenty two adult cats, distributed in four groups, stainless steel electrodes were implanted in the superior colliculus and the substantia nigra of both sides in order: 1) to find the current intensity threshold values necessary to evoke turning behavior, and record their variations after lesion of the cited structures; 2) to study the effects of lesioning two of these structures, specifically related to the direction of turning behavior, and 3) to assess the time-course of recovery from postural asymmetry after damaging two structures involved in rotation behavior, located either in the same or in the opposite side, as well as the importance of performing these lesions simultaneously or at different periods. Three main results were observed: 1) a large proportion of lesioned cats showed an increase in threshold values necessary to evoke rotation of the implanted structures located either in the same or in the opposite side; 2) the lesions induced in a significant number of cats a transient postural asymmetry. After lesioning the superior colliculus, the direction of turning was towards the damaged hemisphere. Apomorphine injected fourteen days later demonstrated the existence of an occult asymmetry, and the direction of turning was maintained. In the substantia nigra lesioned animals, the direction of turning, was towards the non-lesioned side. Apomorphine reversed the direction of turning; 3) the cats showed a remarkable capacity to recover from the postural asymmetry produced by the lesion. This experimental series further support the hypothesis of a close functional relationship between structures of both cerebral hemispheres related to turning behavior.     

5-Hydroxytryptophan-induced respiratory recovery after cervical spinal cord hemisection in rats.

The present study investigates the role of serotonin in respiratory recovery after spinal cord injury. Experiments were conducted on C(2) spinal cord hemisected, anesthetized, vagotomized, paralyzed, and artificially ventilated rats in which end-tidal CO(2) was monitored and maintained. Before drug administration, the phrenic nerve ipsilateral to hemisection showed no respiratory-related activity due to the disruption of the descending bulbospinal respiratory pathways by spinal cord hemisection. 5-Hydroxytryptophan (5-HTP), a serotonin precursor, was administrated intravenously. 5-HTP induced time- and dose-dependent increases in respiratory recovery in the phrenic nerve ipsilateral to hemisection. Although the 5-HTP-induced recovery was initially accompanied by an increase in activity in the contralateral phrenic nerve, suggesting an increase in descending respiratory drive, the recovery persisted well after activity in the contralateral nerve returned to predrug levels. 5-HTP-induced effects were reversed by a serotonin receptor antagonist, methysergide. Because experiments were conducted on animals subjected to C(2) spinal cord hemisection, the recovery was most likely mediated by the activation of a latent respiratory pathway spared by the spinal cord injury. The results suggest that serotonin is an important neuromodulator in the unmasking of the latent respiratory pathway after spinal cord injury. In addition, the results also suggest that the maintenance of 5-HTP-induced respiratory recovery may not require a continuous enhancement of central respiratory drive.     

Serotonin(2) receptors mediate respiratory recovery after cervical spinal cord hemisection in adult rats.

The aim of the present study was to specifically investigate the involvement of serotonin [5-hydroxytryptamine (5-HT(2))] receptors in 5-HT-mediated respiratory recovery after cervical hemisection. Experiments were conducted on C(2) spinal cord-hemisected, anesthetized (chloral hydrate, 400 mg/kg ip), vagotomized, pancuronium- paralyzed, and artificially ventilated female Sprague-Dawley rats in which CO(2) levels were monitored and maintained. Twenty-four hours after spinal hemisection, the ipsilateral phrenic nerve displayed no respiratory-related activity indicative of a functionally complete hemisection. Intravenous administration of the 5-HT(2A/2C)-receptor agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) induced respiratory-related activity in the phrenic nerve ipsilateral to hemisection under conditions in which CO(2) was maintained at constant levels and augmented the activity induced under conditions of hypercapnia. The effects of DOI were found to be dose dependent, and the recovery of activity could be maintained for up to 2 h after a single injection. DOI-induced recovery was attenuated by the 5-HT(2)-receptor antagonist ketanserin but not with the 5-HT(2C)-receptor antagonist RS-102221, suggesting that 5-HT(2A) and not necessarily 5-HT(2C) receptors may be involved in the induction of respiratory recovery after cervical spinal cord injury.     

Effect of ageing and vision on limb load asymmetry during quiet stance

Although the identification and characterization of limb load asymmetries during quiet standing has not received much research attention, they may greatly extend our understanding of the upright stance stability control. It seems that the limb load asymmetry factor may serve as a veridical measure of postural stability and thus it can be used for early diagnostic of the age-related decline in balance control. The effects of ageing and of vision on limb load asymmetry (LLA) during quiet stance were studied in 43 healthy subjects (22 elderly, mean age 72.3+/-4.0 yr, and 21 young, mean age 23.9+/-4.8 yr). Postural sway and body weight distribution were recorded while the subject was standing on two adjacent force platforms during two 120 s trials: one trial was performed with the eyes open (EO), while the other trial was with the eyes closed (EC). The results indicate that LLA was greater in the old adults when compared with the young control subjects. The LLA values were correlated with the postural sway magnitudes especially in the anteroposterior direction. Eyes closure which destabilized posture resulted in a significant increase of body weight distribution asymmetry in the elderly but not in the young persons. The limb load difference between EO and EC conditions showed a significantly greater effect of vision on LLA in the elderly compared to the young subjects. The observed differences in the LLA may be attributed to the decline of postural stability control in the elderly. Ageing results in the progressive decline of postural control and usually the nervous system requires more time to complete a balance recovery action. To compensate for such a deficiency, different compensatory strategies are developed. One of them, as evidenced in our study, is preparatory limb unload strategy (a stance asymmetry strategy) which could significantly shorten reaction time in balance recovery.     

Response of NADPH-Diaphorase-Exhibiting Neurons in the Medullar Reticular Formation to High Spinal Cord Injury

1. The effect of hemisection of the cervical spinal cord on NADPH-diaphorase staining in the reticular nuclei of the rabbit medulla was investigated using histochemical technique.2. A quantitative assessment of somal and neuropil NADPH-diaphorase staining was made by an image analyzer in a selected area of each reticular nucleus of the rabbit medulla.3. On the 7th postsurgery day, the highest up-regulation of somatic NADPH-diapho- rase staining was observed in regions regulating cardiorespiratory processes; however, the highest increase of neuropil NADPH-diaphorase staining was found in the reticular nuclei modulating the tonus of postural muscles.4. The degeneration of non-NADPH-diaphorase-stained neurons was detected throughout the reticular formation of the medulla, but the extent of neuronal death did not correlate with the up-regulation of the NADPH-diaphorase staining in the reticular nuclei of the medulla.5. The findings provide evidence that NADPH-diaphorase-exhibiting neurons are refractory to the hemisection of the cervical spinal cord and that the neuronal up-regulation of NADPH-diaphorase at the medullar level is probably not a causative factor leading to the death of the reticulospinal neurons.     

Expression of high activity of ornithine decarboxylase and occurrence of unusual chromophobic cells in anterior pituitary gland of a novel growth-retarded strain of mice, grm/grm

Extremely high activity of ornithine decarboxylase (ODC) was detected in the pituitary gland of growth- retarded mice, grm/grm at 2 months after birth. The elevated enzyme activity gradually decreased to the control level in 14 months after birth. In the pituitary gland of the growth-retarded mice, unusual chromophobic cells were also present from the early stages after birth. The chromophobic cells showed conspicuous proliferations and resulted in a distinct hyperplasia of the tissue after 4 months after birth. These findings suggest that OCD is correlated to the progressive transformation of pituitary cells into the chromophobic cells.     

Postural asymmetry in rats induced by stress and pain stimuli

A significant number of rats (31–68%) subjected to pain stimulation (intraperitoneal injection of 1% or 5% acetic acid, 5 ml/kg), immobilization stress (6 hrs in a supine position) or cold stress (3 hrs at 4–6°C) exhibited postural asymmetry of hind limbs after spinal cord transection at T7 level. The number of rats with right and left limb flexions was approximately equal. Naloxone (2 mg/kg intraperitoneally) prevented the development of postural asymmetry induced by pain and stress stimuli. Postural asymmetry of hind limbs appears to be due to an asymmetric CNS response to stress and pain stimuli. Our data imply that endogenous opioid peptides and opiate receptors may be involved in the regulation of this response.     

Oxytocic activity of plasma and posterior pituitary lobe after ovariectomy and implantation of stilboestrol or progesterone tablets in female rats

The purpose of this work was to compare the oxytocic activity of plasma and posterior pituitary lobe extract in rats after sham operation, ovariectomy and after subcutaneous implantation of stilboestrol or progesterone tablets in ovariectomized rats. On the 5th day after ovariectomy or implantation of hormones, sample of 2 ml of blood were obtained under urethane anaesthesia from the cephalic end of the right external jugular vein, and the animals were killed by decapitation. The posterior pituitary lobe was removed and homogenized in 0.9% NaCl solution acidified with glacial acetic acid. The oxytocic activity of plasma and extracts of the posterior pituitary lobe was determined by the method of Van Dongen and Hays on fragments of lactating rat mammary tissue. On the 5th day after ovariectomy or implantation of stilboestrol the oxytocic activity was found to be significantly increased in the plasma and posterior pituitary lobe, and after progesterone implantation it was decreased in the posterior pituitary lobe.