Unoperated Control Animals Research Articles

Expression of alpha-smooth muscle actin, TGF-β1 and TGF-β type II receptor during connective tissue contraction

Closure of rat mesenteric perforation is considered to occur by connective tissue contraction, a process that has been shown to be stimulated by transforming growth factor-beta 1. In the present study, we assessed the expression of alpha-smooth muscle actin during closure by quantitative-reverse transcription-polymerase chain reaction and in situ hybridization. The expression of transforming growth factor-beta 1 and transforming growth factor-beta type II receptor was also estimated in mesenteric membranes and free peritoneal cells after wounding. A larger expression of alpha-smooth muscle actin was seen around the wound edges compared to unwounded tissue. Both alpha-smooth muscle actin and transforming growth factor-beta type II receptor were expressed during Days 0, 3, 5, 7, and 10. The expression of alpha-smooth muscle actin on Day 5 was > 100 times higher than on Day 0. Transforming growth factor-beta 1 was expressed in both membranes and free peritoneal cells of unoperated control animals but down-regulated after wounding, a finding that has not been reported previously. It reappeared on Days 7 and 10 in free peritoneal cells but not in perforated membranes. The enhanced expression of alpha-smooth muscle actin and down-regulation of transforming growth factor-beta 1 expression after wounding appears to be important phenomena in tissue contraction and repair.

Evaluation of hindpaw position in rats during chronic constriction injury (CCI) produced with different suture materials.

Bennett and Xie (1988) described an experimental peripheral neuropathy that is produced by loosely ligating a rat's left sciatic nerve with chromic gut suture. Four ligations, which are tied tightly enough to constrict the nerve and retard epineurial blood flow, produce a chronic constriction injury (CCI). Maves et al. (1993) reported that if the ligations are tied more loosely (i.e., no retardation of blood flow) than those that produce the CCI, rats exhibit postural changes only when the ligations are of chromic gut. We decided to evaluate effects of different suture materials on the abnormalities in paw position associated with the CCI (Attal et al., 1990). Five groups of rats were included in this study. In three of the groups, the CCI was produced with chromic gut, plain gut, or polyglactin (Vicryl) suture. Rats in the fourth group served as sham injury control animals, and rats in the fifth group served as unoperated control animals. Our results indicate that the position in which the rats held the affected hindpaw varied significantly among treatment groups. Rats whose CCI was induced with chromic gut suture spent more time with the hindpaw in an abnormal position than rats in the other treatment groups. And as compared to rats in the unoperated control group, rats whose CCI was induced with either plain gut or polyglactin suture also spent more time with the hindpaw in an abnormal position. Though these different suture materials produced similar degrees of nerve constriction, the effects on paw position were greater with chromic gut suture. These results suggest that chromic gut suture, when used to produce the CCI, may have more than just a constrictive effect on the sciatic nerve. However, since all suture materials produced changes in paw position, constriction is likely to play an important role in the development of abnormalities in paw position observed in rats with the CCI.

Cerebrospinal fluid β-endorphin in models of hyperalgesia in the rat

Cerebrospinal fluid (CSF) obtained by acute percutaneous puncture of the cisternal membrane of the halothane anesthetized rat has low but measurable concentrations of β-endorphin-like immunoreactivity (β-EPir: 32.8 ± 3.0 pmol/l). Chromatographic separation of β-EPir showed that authentic β-endorphin 1–31 was the main component of β-EPir in cisternal CSF. Subcutaneous injection of 5% formalin in the hind paws did not increase β-EPir in cisternal CSF. Rats with tactile paw hyperalgesia evoked by unilateral ligation of the L 5/6 nerve roots 2 weeks earlier had β-EPir concentrations that did not differ from sham operated or unoperated control animals. In contrast, capsaicin injected in the hindpaws increased the mean β-EPir concentration compared to saline injections ( P = 0.006) 45 min after emerging from anesthesia following injection. These results show that acute activation of C fibers (by capsaicin) will evoke the release of β-endorphin into the CSF, suggesting activation of the β-endorphin terminal systems in the brain/midbrain. The failure of formalin injections to release β-EPir to CSF may be due to specificity of the afferent stimulus evoking β-EPir release, a lower stimulus intensity, and/or the duration of the stimulus generated by formalin. The normal concentrations of β-EPir found in the hyperalgesic state following nerve injury suggest that the supraspinal β-endorphin system does not display tonic changes under such conditions.

Loss of viable neuronal units in the proximal stump as possible cause for poor function recovery following nerve reconstructions

Function recovery after nerve reconstructions is often poor. Could this be caused by a loss of viable neuronal units proximal to the nerve reconstruction? The number of neuronal units (i.e., a motor or sensory neuron, including its axon and axonal branches) in the proximal segments of reconstructed peripheral nerves were studied using a novel magnetic recording technique. In five rabbits a common peroneal nerve was transected and microsurgically reconstructed. After 8 weeks regeneration time the nerve compound action signals were recorded magnetically from the reconstructed as well as from the healthy contralateral peroneal nerve and from peroneal nerves of five unoperated control animals. The amplitudes of the recorded signals were compared and the diameter distribution histograms were calculated. These calculations were based on the conduction distance between the stimulator and the sensor and the conduction velocities of 30 different axon diameter classes ranging from 3 to 18 μm. Our results indicate that there is a reduction of approximately 50% in the number of viable neuronal units at 10 mm proximal to a simple nerve reconstruction after 8 weeks regeneration time. The number of neuronal units innervating a hand is strongly correlated with clinical function in a healthy hand. The reduction in viable neuronal units after a reconstruction, demonstrated in our experiments, corresponds with a frequently clinically observed decrease in function after nerve reconstructions. Therefore, we suggest that the number of viable neuronal units may be a good indicator of final functional recovery.

Female rats are more susceptible to the development of neuropathic pain using the partial sciatic nerve ligation (PSNL) model

A comparison study was conducted to determine if a gender difference could be detected using an animal model for causalgia. The sciatic nerve was tightly ligated so that 1 3 to 1 2 of the nerve thickness was trapped by the ligature, just distal to the point at which the posterior biceps semitendinosus nerve branches off the common sciatic nerve. By measuring paw withdrawal from innocuous stimulation with Von Frey filaments, the percent of rats displaying average mechanical sensitivity of the injured paw that was significantly elevated compared to sham or unoperated control animals (days 22–24) was 28.6% for the male group versus 63.6% for the female group. Our animals did not display a consistent response in withdrawal latency to heat applied to the plantar surface of the foot (hyperpathia). The data suggests that female rats are significantly more susceptible to developing neuropathic pain than male rats using this experimental model for causalgia.

Unilateral Trigeminal Nerve Branch Lesion (V1 and V2) at the Skull Base and Nasal Capsule Growth in Rabbits

The effects of long-term afferent denervation on midfacial and nasal capsule growth after craniofacial or skull base surgery are unknown. Experimental studies suggest that afferent nerves may play a role in regulating craniofacial growth through neurotrophic influences. The present study was designed to assess the effects of nasal capsule afferent (V1 and V2) denervation on nasal capsule growth in the rabbit. Eighteen 1 1/2-week-old rabbits were evenly divided into three groups: unoperated controls, sham controls, and animals with unilateral anterior ethmoid and sphenopalatine nerve lesions. The nerves were lesioned at the skull base with electrocautery through an intraorbital approach at 1 1/2 weeks of age. Lateral head radiographs and dental study models were taken at 1 1/2, 3 1/2, 6, and 12 weeks of age. By 3 1/2 weeks of age, sham controls and animals with nerve lesions exhibited significant (p < 0.05) reductions in nasal capsule area and height compared with unoperated control animals; the lesioned animals were more severely affected. However, by 6 weeks no differences were noted between the sham and lesioned groups, which were both smaller than unoperated controls through 12 weeks of age. Results suggest that acute nasal capsule growth deficits are a consequence of surgery as well as afferent denervation, with a greater deficit in the latter group, possibly through neurotrophic interruption. Such deficits may not be a permanent effect in the rabbit model.

Alterations in Hypothalamic μ–Opiate Receptor—Mediated Responses But Not Methionine Enkephalin or Proenkephalin Messenger Rna Levels in Rats With Acute Cholestasis

Endogenous opioids, including methionine enkephalin, have been implicated in the control of adrenocorticotrophic hormone release by acting through mu-opiate receptors in the hypothalamus. Recently, alterations in the central opioid system have been postulated to occur in cholestasis. In addition, alterations in hypothalamic corticotropin-releasing hormone content and messenger RNA levels, as well as basal release, have been described in bile duct-resected rats, and hypothalamic methionine enkephalin is colocalized with corticotropin-releasing hormone in hypothalamic neurons. Therefore hypothalamic and pituitary methionine enkephalin content and hypothalamic proenkephalin messenger RNA levels, as well as hypothalamic mu-opiate receptor-mediated responses in vitro and in vivo, were studied in rats with acute cholestasis caused by bile duct resection and in respective controls. Hypothalamic and pituitary methionine enkephalin levels were similar in bile duct-resected, sham-resected and unoperated control rats. In addition, hypothalamic proenkephalin steady state messenger RNA levels were similar in the three groups of animals. mu-Opiate receptor stimulation of hypothalamic explants in vitro with the specific mu-opiate receptor agonist ligand [D-Ala2,N-Me-Phe4,Gly-ol]-Enkephalin resulted in 8.2% and 16.9% inhibition of corticotropin-releasing hormone release in sham-resected and unoperated control rats, respectively. In contrast, treatment of hypothalamic explants from bile duct-resected rats with [D-Ala2,N-Me-Phe4,Gly-ol]-Enkephalin resulted in a significant 22.5% increase in corticotropin-releasing hormone release. Systemic administration of the mu-opiate receptor agonist morphine to rats in vivo resulted in significantly higher incremental rises in plasma adrenocorticotropic hormone levels in sham-resected and unoperated control animals than in bile duct-resected rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Restoration of Spermatogenesis and Subsequent Fertility by Direct Intratesticular Hormonal Therapy

Testosterone-laden microspheres (TLM) were used in an attempt to restore spermatogenesis and sustain fertility in rats with previously suppressed gonadal function. Adult rats received 62.5μg. gonadotropin-releasing hormone antagonist (GnRH-antagonist) per day for 15 days prior to being divided into three groups: 1) animals to be examined immediately, 2) animals to continue receiving 62.5μg. GnRH-antagonist per day alone, and 3) animals to continue receiving GnRH-antagonist + a single intratesticular injection of 20mg. TLM per testis. Unoperated control and sham-operated animals were also studied. Testicular interstitial fluid (TIF) testosterone concentrations, testicular sperm production and fertility were assessed 105 days after initiation of the experiment. Testicular interstitial fluid testosterone concentrations and sperm production were significantly reduced from control values after the initial 15-day GnRH-antagonist treatment (p < .05). After 105 days of GnRH-antagonist treatment, these values were further reduced (p < .05), but the TIF testosterone and sperm production values of GnRH-antagonist treated animals receiving TLM supplementation were not different from those of controls (p < .05). Fertility trials were also performed. Animals which had received GnRH-antagonist alone for 90 days were completely infertile, but animals receiving GnRH-antagonist + TLM for 90 days had fertility values not different from those of control animals (p < .05). Thus, spermatogenesis reduced because of testicular insufficiency was restored to normal, as was fertility, by intratesticular administration of TLM. This technique has possible clinical applications in selected groups of infertile men.

Neonatal nerve injury causes long-term changes in growth and distribution of motoneuron dendrites in the rat

Disruption of neuromuscular contact by nerve-crush during the early postnatal period results in the death of a large proportion of affected motoneurons. Increased activity and abnormal reflex responses are evident in those that survive. We have studied the aberrant dendritic morphology of surviving cells and have attempted to correlate the observed alterations in morphology with the above experimental findings. Motoneurons supplying the extensor hallucis longus muscles of the rat were retrogradely labelled with cholera toxin subunit-B conjugated to horseradish peroxidase. The dendritic tree of labelled cells was analysed in adult animals having undergone unilateral sciatic nerve-crush at birth. Unoperated control animals were also examined. Following nerve-crush at birth, total visible dendritic length was more than 30% smaller than control cells in the transverse plane. This decrease was confined largely to the medially directed segments of the dendritic field and appeared to be due to a reduction in dendritic branching combined with a failure to achieve the correct branch length. There was no overall change in total visible dendritic length in the longitudinal plane, but a reorientation of dendrites in favour of rostrodorsal regions was observed. There was no alteration in dendritic length in cells contralateral to the nerve injury. These results show that nerve injury during early postnatal development produces lasting changes in the distribution of motoneuron dendrites. The localized nature of these changes may explain the altered activity and induced death of motoneurons seen after neonatal nerve-crush.

The effects of stress on splenic immune function are mediated by the splenic nerve

Intermittent footshock (FS) suppresses immune function of spleen cells. To determine if the autonomie nervous system mediates this immunosuppression in spleen cells, we tested whether cutting the splenic nerve, which depletes splenic norepinephrine levels by 98–100% and eliminates catecholamine fibers, blocks the effects of stress. Splenic nerve sections, sham operations, or no surgery were performed on male Sprague-Dawley rats. Ten days later, rats were injected with sheep red blood cells (SRBC). Three days later, rats were placed in a chamber equipped with a shock grid. Foot shock (1.6 mA) was administered for 5 s on a VI 3.5 min schedule for 60 min. Each FS was preceded by a 15-s warning tone. Controls were treated identically except for the FS. The next day spleen cells were harvested and the number of IgM plaque-forming cells (PFCs) determined. For the sham and unoperated control animals, the number of PFCs was reduced for the stressed animals relative to the nonstressed controls, and there was no effect of the sham surgeries. In contrast, there was no difference between the stressed and nonstressed groups in which the splenic nerve had been sectioned, and their PFC response was comparable to the controls. Next we examined the effects of FS on the proliferative response to mitogens (PHA and ConA) following splenic nerve sections or sham operations. One week following surgery, animals were given a 60-min session of FS or exposed to the chamber/tone without FS. Rats were then killed, spleens harvested, and the proliferative response to mitogens determined. Foot shock suppressed the response to mitogens in the sham rats, relative to the sham-operated animals not exposed to FS. In contrast, there was no difference between the stressed and nonstressed groups in which the splenic nerve had been cut, and their proliferative responses were comparable to the nonstressed-sham animals. Thus, the effects of stress on the PFC response and the proliferative response of spleen cells is mediated via the splenic nerve. These results indicate that the sympathetic nervous system is a fundamental and significant mediator of brain-immune interactions.

Central sites mediating reproductive responses to melatonin in juvenile male Siberian hamsters

Juvenile male Siberian hamsters received infusions of varying doses of melatonin (MEL), or saline vehicle, via microdialysis probes implanted in brain regions which have previously been shown to contain MEL receptors. Daily infusions were 10 h in length and occurred during exposure to constant light on days 22–34 of age. All animals were sacrificed on day 35 and paired testis weights recorded prior to preparation of the brain tissue for histological evaluation of the infusion site. Some animals were also blood-sampled prior to sacrifice for determination of circulating levels of prolactin (PRL). Saline infusions did not have a significant effect upon gonadal maturation, regardless of the infusion site, when compared with unoperated control animals reared under similar photoperiod conditions. In contrast, animals which received infusions of 75 pg MEL into the suprachiasmatic nucleus (SCN), paraventricular nucleus of the thalamus, or nucleus reuniens regions, showed a marked inhibition of gonadal growth. Infusions of this dose of MEL into various other neural regions (e.g. lateral hypothalamus, ventromedial nucleus of the hypothalamus, paraventricular nucleus of the hypothalamus) did not result in decreased testis weights at the time of sacrifice. Daily administration of 20 pg MEL inhibited gonadal maturation and resulted in decreased circulating PRL levels only when infused into the SCN region. For animals receiving the 7.5 pg dose, infusions into the midline thalamic nuclei were not successful in inhibiting testis growth, and infusions in the SCN region had only a marginal effect. These results indicate that endogenous MEL may influence at least one seasonal response in this species, i.e. reproductive responses to photoperiod, by acting at some or all of these central MEL binding sites.

Immunosuppression in nerve allografting: is it desirable?

Immunologically incompatible sciatic nerve grafts were inserted into the severed sciatic nerves of Wistar rats. In an attempt to induce graft tolerance, low-dose cyclosporin A (CsA) was administered to some animals for 20 weeks, then gradually withdrawn. Behavioural, electrophysiological and histological studies indicated that some degree of regeneration took place in all animals regardless of treatment. Neither a daily dose of 5 mg/kg nor 10 mg/kg was sufficient to prevent the rejection and subsequent disruption of allograft structure, and as a consequence reinnervation of the distal stump was limited. This was manifest both in the poor functional recovery of the denervated foot, and in the large number of regenerated axons found outside of the perineurial membranes of the transplanted fascicles. Therefore tolerance was not induced at these doses. Furthermore, the significant decrease in the amplitude of electromyographs recorded from experimental and unoperated (control) animals suggests CsA may have a deleterious effect on unlesioned nerve even at these low doses. it would be prudent, therefore, to exercise caution in the combined used of nerve allografts and CsA immunosuppression, until the neurotoxicity of CsA has been investigated further. This is particularly important since CsA is sometimes used in the treatment of certain neuropathic autoimmune diseases.

Effect of partial denervation on motor units in the ageing rat medial gastronemius

The ageing neuromuscular system is thought to undergo a continual process of reorganization as motoneurones are lost and surviving motor nerves reinnervate neighbouring denervated muscle fibres. However, the extent to which collateral reinnervation is able to compensate for neural deficits in the ageing individual is unknown. The ability of the senscent motoneurone to increase the size of its peripheral field was therefore investigated following transection of the right L 5 ventral root in male Sprague Dawley rats aged 775 ± 50 days. This procedure resulted in an extenssive partial denervation of the right medial gastroscemius muscle. After a recovery period of between 28 and 31 days the isometric contractile properties of surviving motor units were compared to control units from both the contralateral muscle and a group of unoperated control animals aged 791 ± 39 days. Motor unit force was found to be unchanged after partial denervation and the absence of any alteration in motor unit size was confirmed by histological analysis. However, the time course of the isometric twitch was significantly longer for both fast and slow motor unit types and the conduction velocity of motoneurones innervating fast unitswas decreased following partial denervation. These results demonstrate that senescent motor nerves are unable to substantially increase the size of their peripheral fields by extensive collateral reinnervation.

Electrophysiological responses in the rat tail artery during reinnervation following lesions of the sympathetic supply.

1. Responses to perivascular stimuli have been recorded with intracellular microelectrodes from the smooth muscle of isolated segments of the main caudal artery of rats at various times between 7 and 128 days after all four collector nerve trunks had been lesioned near the base of the tail at 21 days of age. 2. In proximal segments (< 40 mm distal to the lesions), excitatory junction potentials (EJPs) and neurogenic alpha-depolarizations (NADs) evoked by stimuli presented via a proximally located suction electrode were similar to those in the same segments of unoperated control animals of the same age. Supramaximal EJPs in these segments decreased in amplitude with age. 3. Stimuli just supramaximal for EJPs in innervated preparations failed to evoke responses in segments farther than 30-40 mm distal to the lesions at any time after the nerves had been cut and 1 cm excised. Higher voltages evoked slow depolarizing potentials (SDPs) which were of longer time course than EJPs. Similar responses occurred in segments over 60 mm distal to the lesions at 20-50 days after the nerves had been frozen, and in all segments sampled over 100 mm distal to nerve lesions. 4. Spontaneous transient depolarizations (STDs) were recorded at all depths of the media in denervated segments. These occurred at frequencies similar to those of spontaneous events (including attenuated spontaneous EJPs) in innervated segments. 5. The earliest signs of reinnervation (24-42 days after freeze lesions) consisted of very small amplitude EJPs of normal time course which facilitated markedly during a short train of stimuli (5-10 Hz); these were followed by NADs which were large relative to the amplitudes of the EJPs. Less commonly, small focal EJPs of brief time course (resembling spontaneous EJPs in superficial cells of innervated arteries) were evoked in very restricted regions of the vessel wall. 6. At later times (57-128 days postoperative), six of eight segments located 40-70 mm distal to freeze lesions showed EJPs of nearly control amplitude, but NADs that were larger than in equivalent segments from control animals. In the remaining two cases, reinnervation at this level was similar to that seen at the earliest postoperative times. High stimulus voltages prolonged the decay of EJPs in both control and reinnervated arteries. 7. Sensitivity to exogenous noradrenaline, assessed in terms of membrane depolarization, was increased in both denervated and reinnervated segments. 8. Catecholamine fluorescence disappeared from the arteries at a distance greater than 30-40 mm distal to the site of the nerve lesions.(ABSTRACT TRUNCATED AT 400 WORDS)

Nucleus basalis lesions attenuate acquisition, but not retention, of Pavlovian heart rate conditioning and have no effect on eyeblink conditioning.

Rabbits with lesions of the anterior nucleus basalis of Meynert (nBM) were compared with animals with sham lesions or unoperated control animals on a classical conditioning task in which heart rate (HR) and eyeblink (EB) conditioned responses (CRs) were assessed. The nBM lesions impaired the magnitude of the decelerative HR CR, but had no effect on the EB CR. A second experiment, in which animals were lesioned after acquisition was complete, showed that anterior nBM lesions had no effect on retention of either the HR or EB CR. These data suggest that the anterior nBM may participate in the early stages of information processing in which stimuli are evaluated for their significance based on their association with a reinforcer. However, the anterior nBM is apparently not involved in the selection of a somatomotor response to deal effectively with such changing stimulus contingencies.

A comparative study of mandibular growth patterns in seven animal models

The use of nonhuman primate experimental models has helped make significant contributions toward the clinical and surgical management of patients with craniofacial disorders. With concerns such as increasing cost, however, alternative models will have to be identified. The present comparative study describes baseline, age-related changes in mandibular growth patterns for seven commonly used animal models. The data was obtained from 144 serial and cross-sectional lateral head radiographs of unoperated control animals from a number of previous craniofacial growth studies. The sample consisted of 26 rats, 21 rabbits, 21 domestic cats, 23 domestic dogs, 17 baboons, 16 rhesus monkeys, and 20 chimpanzees. Comparative human data were taken from the Bolton Standards. The samples were divided into three age categories: infant, juvenile, and adult. Mandibular growth measurements included overall mandibular length, ramal height, and body height. Comparative analysis consisted of the calculation of percent increase from the infant condition. For all measurements, three major clusters could be discerned: 1) humans, chimps, and rhesus monkeys; 2) dogs and baboons; and 3) cats, rats, and rabbits. Results suggested that for the dimensions studied, long-term mandibular growth was best modeled by short-faced primates, and in particular, the chimpanzee. In addition, dogs and rats showed similar relative percent changes in different regions from juvenile through adulthood stages, which suggests that these animals may be acceptable, inexpensive alternatives to primates in certain experimental situations.

The influence of ageing on wound healing of the cricoid.

In young and adult rabbits the effects of one anterior or two bilateral splits of the cricoid were studied. Interruption of the cricoid ring elicits wound healing of the cut edges and induces changes in form and size of the separated parts of the cricoid (indirect effect). It was demonstrated that with increasing age i) the wound healing capacities of the hyaline cartilage is highly diminished or lost and ii) the induced remodelling, involving the total ring in young animals, is in the adult stage confined to the posterior part. Moreover, the observations suggest that dividing the cricoid ring in an anterior and posterior part at a young age can result in a stimulation of growth of the anterior part, in comparison with unoperated control animals.

Comparison of the electrical properties of arterial smooth muscle in normotensive rats and rats with deoxycorticosterone acetate-salt-induced hypertension: possible involvement of (Na(+)-K(+)-Cl-) co-transport.

1. Hypertension was induced in male Sprague-Dawley rats by left unilateral nephrectomy and deoxycorticosterone acetate--salt administration. After 5 weeks, arterial systolic blood pressure was significantly elevated in these animals (191.5 +/- 6.0 mmHg, mean +/- SD, n = 17) compared with age-matched, unoperated control animals (134.0 +/- 4.2 mmHg, n = 8, P less than 0.001). 2. The membrane potential of femoral artery vascular smooth muscle measured in vitro was -55.1 +/- 6.3 mV (mean +/- SD, n = 154) for normotensive and -50.8 +/- 5.7 mV (n = 82) for hypertensive animals. The difference in membrane potential was significant (P less than 0.001). 3. The relationship between the log of the extracellular K+ concentration and membrane potential was nonlinear over the extracellular K+ concentration range 2.5-20 mmol/l, and showed a small positive shift with hypertension. 4. Tenfold reductions in the extracellular concentrations of Na+ or Cl- resulted in a membrane potential hyperpolarization in vascular smooth muscle from normotensive animals (4.9 +/- 2.0 mV, n = 13 and 12.1 +/- 1.3 mV, mean +/- SD, n = 14, respectively). In vascular smooth muscle from hypertensive animals, the hyperpolarization in low-Na+ media was significantly increased to 12.2 +/- 2.6 mV (mean +/- SD, n = 5), but that in low-Cl- media was unaffected (2.7 +/- 1.6 mV, n = 6). 5. The loop diuretic, bumetanide (10 mumol/l), hyperpolarized the membrane potential in vascular smooth muscle from both normotensive and hypertensive rats, but not in low-Na+ or low-Cl- media.(ABSTRACT TRUNCATED AT 250 WORDS)

Interactions between callosal, thalamic and associational projections to the visual cortex of the developing rat

The patterns of callosal interconnections between the visual cortices of rats display considerable plasticity in response to various neonatal manipulations. In the present study, many neurones in the principal visual thalamic relay nuclei, the dorsal lateral geniculate nucleus (DLG) and to a lesser extent those in the lateral posterior nucleus (LP) were destroyed by injections of the neurotoxin - kainic acid - on the first day of postnatal life. Four weeks later, as demonstrated with the anterograde and retrograde transport of the enzyme horseradish peroxidase (HRP) injected into the occipital lobe of one hemisphere, callosally projecting neurones and terminals were distributed more widely in the retinotopically organized areas 17, 18a and 18b of the visual cortex ipsilateral to the lesioned visual thalamus than in unoperated control animals of the same age. By contrast, in the visual cortex contralateral to the lesioned visual thalamus the areal distribution of callosally projecting neurones and terminals was similar to that of the controls, that is, largely but not exclusively restricted to the common border of areas 17 and 18a. Both in unoperated and operated animals, cells in lamina V of several cytoarchitectonically defined areas that are not retinotopically organized (area 8 in the frontal lobe, area 29d in the retrosplenial limbic cortex and perirhinal areas 35/13 in the temporal lobe) also project to contralateral visual cortices. In areas 8 and 29d, the total numbers, laminar distributions and densities of labelled callosal cells both ipsilateral and contralateral to the kainate-injected visual thalamus were similar to those in the controls. However, in the temporal lobe, the areal distribution of the labelled callosal neurones was more extensive than that in the controls and labelled cells in areas 35/13 of the cortex contralateral to the kainate-lesioned visual thalamus merged with those in the neighbouring areas 20 and 36. By contrast, the areal distribution of associational neurones in area 18a and in nonretinotopically organized areas projecting to area 17 were very similar in controls and in operated animals (neonatal kainate lesion of the visual thalamus, neonatal section of the corpus callosum or both procedures combined). However, in operated animals, the labelled associational neurones projecting from the supragranular laminae (II/III) of area 18a to area 17 constituted a higher proportion of all cells than did those in the unoperated control animals. Thus, overall the number of associational neurones projecting from area 18a to area 17 was slightly increased by the experimental manipulations performed.(ABSTRACT TRUNCATED AT 400 WORDS)

Ultrastructural changes in the gracile nucleus of the rat after sciatic nerve transection

Ultrastructural changes in the gracile nucleus of the rat have been examined after peripheral nerve injury. The sciatic nerve of adult rats was transected at mid-thigh level, and after survival times ranging from 1 day to 32 weeks sections from the gracile nucleus were prepared for electron microscopic examination. Unoperated animals served as controls. Atypical profiles were regularly observed in the experimental cases at post-operative survival times from 3 days up to 32 weeks. It was sometimes not possible to classify these as preterminal axons or terminals, because synaptic contacts could not be identified. The two most common changes throughout the entire post-operative period were greatly expanded myelinated axons, or unmyelinated profiles containing numerous mitochondria, osmiophilic dense bodies and vacuoles. Atypical profiles were occasionally observed in unoperated control animals. The results clearly show that various types of degenerative changes occur in the gracile nucleus after peripheral nerve injury. These changes differ markedly from previously described transganglionic changes in other systems. It cannot be excluded that some of the changes reflect growth-related reactions, although the typical features of axon regeneration could not be found.