Reticular Lesions Research Articles

Histologic changes associated with the topical use of isotretinoin on oral lichen planus

B 0th systemic and topical synthetic retinoids (vitamin A derivatives) have been used extensively in the treatment of keratotic skin diseases that feature abnormal epithelial cell proliferation and differentiation. Dramatic results have been reported following the treatment of psoriasis and acne with etretinate and isotretinoin (13~cis retinoic acid).‘-4 Because of the antikeratinizing and immunomodulating effects of retinoids,‘.4*s the use of these compounds has been extended to the treatment of patients with cutaneous and oral lichen planus. Systemic retinoids-etretinate, isotretinoin, and tretinoin (all-trans retinoic acid)-have produced clinically significant results in patients with oral lichen planus.‘-l3 In one study, however, only marginal improvement was noted in patients with erosive lichen planus. I4 Because of side effects, the investigators thought that treatment with systemic etretinate did not justify the results. Topical tretinoin has produced generally good results in patients with oral lichen planus, without the complications of cheilitis, dry skin, eievation of serum liver enzymes, and elevation of serum triglycerides and cholesterol that are commonly associated with systemic therapy. ‘. ‘w’ Until recently, studies using topical agents have been limited to the use of tretinoin. A related retinoid-isotretinoin-had been made available to us in a 0.1% gel for clinical testing and showed considerable efficacy in the treatment of oral lichen planus. I8 Atrophic and erosive lesions responded less dramatically than reticular lesions. This double-blind clinical trial spanned 8 weeks of twice-daily application of isotretinoin gel (Figs. 1

Bilateral horizontal gaze paralysis due to pontine hemorrhage: A case report

In a case of bilateral horizontal gaze paralysis, vertical gaze was clinically intact but eye movement recordings demonstrated a transient reduction of vertical saccadic velocities. Horizontal caloric vestibulo-ocular responses were absent. CT scanning and NMR imaging showed a hematoma in the median pontine tegmentum. This case provides additional evidence that vertical and horizontal saccade genesis may be independent of caudal paramedian pontine reticular formation lesions.

The inhibitory role of the visually responsive region of the thalamic reticular nucleus in the rat.

Two-shock inhibition, a feature of 98 of 100 P cells recorded in the dorsal lateral geniculate nucleus of the normal rat, was not observed in 91 of 140 geniculate cells after an electrolytic lesion had been made in the adjacent visually responsive thalamic reticular nucleus. Nine geniculate cells recorded both before and after a reticular lesion had their initial inhibition abolished or substantially reduced after the lesion. The reticular lesion eliminated the bursts of spikes which normally terminate periods of inhibition following electrical or photic stimulation but caused no other changes in receptive field organization of geniculate cells. We conclude that the visually responsive region of the thalamic reticular nucleus in the rat is responsible for the profound two-shock inhibition and for the post-inhibitory bursts which are normal properties of relay cells of the dorsal lateral geniculate nucleus.

A generalized learning deficit in albino rats with early median raphe or pontine reticular formation lesions

Recent studies suggest that lesions of the median raphe or pontine reticular formation in adult rats are associated with a nonspecific (generalized) learning impairment. The present study showed that lesions in the region of the median raphe or pontine reticular formation in 21 day old rats likewise produced a nonspecific learning impairment, as evidence by significant deficits on a visual discrimination, nonvisual incline plane discrimination, 3-cul maze, and three simple spatial problems. The finding that relatively large lateral pontomesencephalic lesions did not lead to deficient learning of any of these tasks indicates that lesion locus rather than lesion size is responsible for the production of the learning deficits observed in this study.

Effects of lateral reticular nucleus lesions on the exercise pressor reflex in cats.

Effects of lateral reticular nucleus lesions on the exercise pressor reflex in cats.

Retention of individual spatial reversal problems in rats with nigral, caudoputamenal, and reticular formation lesions

Rats with bilateral nigral, caudoputamenal, or midbrain reticular formation lesions display impairment in learning position reversal problems in a simple T maze. Test trials given after learning each reversal problem disclose defective retention only in the nigral and caudoputamenal groups. This pattern of deficits associated with nigro-neostriatal damage is similar to that reported earlier in rats with bilateral lesions in the vicinity of the parafascicular nucleus. It is proposed that the nigral—parafascicular—neostriatal complex contributes to consolidation of spatial information in rodents.

Effects of mesencephalic reticular formation lesions on habituation of startle and lick suppression responses in the rat.

Extensive damage to the mesencephalic reticular formation (MRF) in rats altered long-term habituation of the acoustic startle response without disrupting short-term habituation. Animals with MRF lesions, although initially neither more nor less responsive than controls, could not attain as low a long-term asymptote of habituation as could control animals with repeated presentations of an auditory stimulus. Changing the quality of the auditory stimulus abolished the asymptotic difference in responsiveness. With repeated presentations of the second auditory stimulus, control animals again reached a significantly lower long-term habituation asymptote than did animals with MRF lesions. The course of long-term habituation for the two groups suggested a disruption of an extrinsic, inhibitory habituation process by the lesions. The effects of MRF lesions were specific to the acoustic startle response. Control animals and those with lesions showed comparable response levels, short-term habituation, and long-term habituation of the lick suppression response. responsiveness and habituation to tactile stimuli were comparable for the two groups in both lick suppression and startle response measures.

Effects of ipsilateral rostral pontine reticular lesions on retention of classically conditioned nictitating membrane and eyelid responses

Neural unit recordings from the pontine reticular formation in well-trained rabbits show a tone-evoked onset response (CS), a suggestion of an airpuff onset response (UCS), and an increase in unit activity that is similar to the topography of the learned response. When this same area is destroyed by unilateral electrolytic lesions (in another group of animals), retention of the learned response is abolished but the reflex response is essentially unchanged. Since a recent study (McCormick, Lavond, Clark, Kettner, Rising, & Thompson, 1981) has shown that unilateral cerebellar lesions also produce a complete and selective abolition of the CR, and the CR cannot be reinstated with retraining, these findings are discussed in terms of a common circuitry that encodes the engram for short-delay classical conditioning of striated muscle responses.

Medullary reticular formation lesions and lordosis reflex in female rats

Medullary reticular formation lesions and lordosis reflex in female rats

Effects of median raphe nucleus lesions on hippocampal EEG in the freely moving rat

The effects of median raphe lesions on the hippocampal EEG were examined in freely moving rats. First, median raphe lesions, including those restricted to the median raphe nucleus, unequivocally produced hippocampal low-frequency theta activity (5.8 Hz, SD= 0.47 Hz) during relaxed immobility which was not observed under normal conditions. This lesion-induced theta activity during immobility continued for at least 20 days, and was markedly suppressed by atropine sulfate (10 mg/kg, i.p.). On the other hand, reticular formation lesions had little effect on either hippocampal EEG patterns during immobility, movement or PS. Second, the mean frequency of theta activity was significantly reduced during movement and PS on the day following the median raphe lesion. These findings suggest a raphe-hippocampal pathway in which the median raphe nucleus plays a major role in hippocampal desynchronization (irregular pattern) by exerting an inhibitory influence on the hippocompal theta generating or facilitating mechanism. Thus the theta activity will be induced by the disinhibition following median raphe lesions.

Nonsensory neglect.

Five monkeys trained to perform with the extremity contralateral to a stimulus had unilateral neglect induced by frontal and reticular formation lesions. Postoperatively the performance of the animals was abnormal only on ipsilateral stimulation, which suggests that the mechanism underlying neglect in these subjects is not deafferentation of sensory inattention but a defect of intention.

The cortical electromicrophysiology of pathological delta waves in the electroencephalogram of cats

Pathological delta waves produced by lesions of the subcortical white matter, the mesencephalic reticular formation or of the thalamus show similar microphysiological features. Computer analysis of the relationship between these delta waves and cortical unit discharges demonstrate that the latter are statistically correlated with surface positivity of the delta waves, while surface negativity is correlated with a significant reduction of probability of discharge of cortical neurons. These findings suggest that surface positive delta waves may represent the sums of deep intracortical EPSPs, while surface negative waves may represent the sums of deep intracortical IPSPs. The unit-slow wave relationships for delta waves induced by thalamic lesions were, however, more variable and often less clearcut than for those induced by lesions of the white matter or of the mesencephalic reticular formation. Also the thalamically induced delta waves occasionally showed increased probability of unit discharge with surface negativity and a decrease with surface positivity. Laminar profiles of the three types of delta waves were plotted by means of a computer averaging program. Delta waves produced by white matter lesions showed phase reversal at a mean cortical depth of 965 ± 160 μm. The corresponding figure for delta waves produced by mesencephalic reticular formation lesions was 1380 ± 375 μm. (The two values are significantly different, P > 0.005). For slow waves induced by thalamic lesions phase reversals occurred at more variable depths and were often difficult to establish. Generally, delta waves decreased greatly in amplitude with increasing depth in the cortex; this was also true for phase inverted waves in the depth. In about 1 out of 4 instances, the amplitude reduction in the depth was such that the delta wave was no longer detectable in the deeper cortical layers and no phase inversion could be established. Tangential surface recordings of delta waves showed that there was no significant current flow over small distances. These findings indicate that delta waves are generated by radially oriented cellular elements. Pyramidal neurons, particularly those of the Vth cortical layer, qualify for this role. In the light of our findings a significant contribution by glial cells to delta wave production can be ruled out.

The role of mesencephalic structures in thirst induced by centrally administered angiotensin II

(1) In 27 animals microinjection of 25–100 ng of angiotensin II through chronic cannulae implanted in the preoptic region initiated drinking and in subsequent acute experiments influenced the spontaneous discharge rate of single neurons in the ipsilateral mesencephalon. Of 148 neurons for which recordings were made, 52 (35%) increased their frequency of spike potentials following administration of angiotensin II, 2 (1%) showed inhibition and 94 (64%) showed no change in firing rate. (2) In another series of 44 animals, unilateral or bilateral lesions of the midbrain ventral tegmentum or reticular formation were found to have little or no effect on water intake elicited by the microinjection of angiotensin II into the preoptic region. (3) In contrast to the effects of tegmental and reticular lesions, unilateral lesions located dorsally and laterally to the mammillary peduncle, in the area of passage of the medial forebrain bundle, significantly attenuated the dipsogenic response to either contralateral or ipsilateral injections of angiotensin II into the preoptic region. With bilateral lesions this effect was permanent. (4) Since the more caudal lesions were relatively ineffective in disrupting the elicited drinking, it is suggested that signals from angiotensin II receptors in the preoptic region are transmitted along pathways which diverge in the midbrain. (5) The possibility of a forebrain-hypothalamus-midbrain circuit mediating thirst initiated by activation of the renin-angiotensin system is discussed.

The lateral reticular nucleus in the cat—II. Effects of lateral reticular lesions on posture and reflex movements

Unilateral lesion of the lateral reticular nucleus produced a postural asymmetry characterized by ipsilateral hypertonia and contralateral hypotonia of the limb extensor muscles. Soon after the operation the cat was unable to stand or walk, and it laid on one side. Within 3 days, it began to walk, but it often deviated to its contralateral side, 'frequently falling in this direction. Some compensation for both postural and motor deficits occurred in chronic preparations maintained up to 154 days after the lesion. The postural asymmetry was reversed by the following operations: (1) section of the ipsilateral VIIIth nerve, (2) electrolytic lesion of the ipsilateral Deiters' nucleus, or (3) ablation of the contralateral vermal cortex of the cerebellar anterior lobe. The lateral reticular nucleus lesion also produced, in the ipsilateral limbs, a transient loss of the proprioceptive placing reaction and a persistent deficit of the tactile placing reflex. These effects on the ipsilateral side were not reversed by the procedures described above. All of these behaviors depended on selective destruction of the lateral reticular nucleus and were not due to damage to the nearby main reticular formation or ascending and descending pathways. Moreover, the postural changes did not involve mesencephalic or higher mechanisms, since they were still observed after decerebration. The forelimbs were affected primarily by lesions involving the dorsomedial, magnocellular part of the lateral reticular nucleus, whereas the hindlimbs also were affected by lesions including the ventrolateral, parvicellular part of the lateral reticular nucleus. The postural asymmetry is attributed to interruption of the crossed spinoreticulocerebellar pathway, acting on the vermal cortex of the anterior lobe and the fastigial nucleus, while the ipsilateral loss of the placing reaction is attributed to interruption of the uncrossed spinoreticulocerebellar pathway acting on the intermediate cortex of the anterior lobe and the interpositus nucleus. The lateral reticular nucleus appears, therefore, to be composed of two, more or less independent, parts, a crossed one being related to major changes in postural tone, equilibrium and locomotion of the entire body, and an uncrossed one restricted to discrete movements of the ipsilateral limbs.

Brain stem projections to the striatum: Experimental morphological studies in the rat

Projections from the brain stem to the striatum were investigated in experiments employing anterograde degeneration and retrograde transport techniques. Following lesions of the substantia nigra of one hemisphere and mesencephalic or pontine reticular formation lesions of the other hemisphere, degenerating axons were traced through the diencephalon and terminal degeneration mapped in the striatal complex. Although degeneration resulting from lesions of the substantia nigra is much more dense than that from lesions of the reticular formation, there is a good deal of overlap in the distribution of the terminal fields. Following micro-injections of horseradish peroxidase into the striatum, cell bodies labeled by peroxidase are observed in the substantia nigra, and in caudal mesencephalic and pontine reticular formation. The substantia nigra is labeled much more heavily than is the reticular formation, both in percentage of cells labeled and in intensity of the label in individual cells. The results are discussed in light of other morphological and electrophysiological data on brain stem-striatal projections.

Bilateral sensory neglect following midsagittal reticular formation lesions in cats.

We have observed that midsagittal reticular formation lesions in cats produce bilateral deficits in attention to and localization of various sensory modalities. To correlate these changes with previously reported changes following lesions in other areas of the brain, we propose the existence of two interdependent inhibitory pathways which originate in the frontal lobes.

Variations in Motility Associated with Striatal Acetylcholine Levels

In the course of investigations of interstriatal relationships, studied with electrical stimulation, small unilateral lesions were placed into the dorsomedial reticular formation of rats at the superior collicular level. Following the placement of these lesions, the amplitudes of the summed and averaged interstriatal responses were greatly increased. A clinical correlate was reduction of the speed of locomotion, at times advancing to complete akinesia, catatonia, and frequently generalized clonus. The acetylcholine (Ach) level (as determined in five control animals) rose from the mean striatal level of 6.5 <i>µ</i>g/g (±1.02) by 100% to 13.3 <i>µ</i>g/g (±1.16) 6–8 h after the reticular lesion was placed. The Ach level was determined according to the method of Crossland after the animals were killed in liquid nitrogen. We then placed in a series of other rats large lesions into the amygdaloid complex, including the origin of the stria terminalis. Catalepsy did not occur when this procedure was followed by injury to the midbrain tegmentum. These rats showed spontaneous locomotion, and clonic seizures appeared only infrequently. In these animals, the mean amount of Ach in the striata was only slightly elevated to 7.1 <i>µ</i>g/g (±0.76). The elevation of Ach in the striate, produced in the previous set of experiments by lesions in the reticular formations, was prevented by the prior placement of amygdaloid lesions. In addition, the amygdaloid lesion prevented an increase of amplitude of the interstriatally evoked and recorded responses. Symmetrel (amantadine hydrochloride) is known to enhance dopamine turnover in the striata of untreated rats. It also increases spontaneous running speed during the initial dosages. Thereafter, repeated daily administration of large doses of Symmetrel was followed by decreased locomotion and eventually bradykinesia or akinesia with rigidity. In these rats, the striatal Ach level increased to 10.7 <i>µ</i>g/g (± 0.92). Since the above mentioned experimental catatonia developed as a consequence of striatal excitation associated with Ach increase, we followed this line of experiments in another group of rats with subcutaneous injections of small amounts of bulbocapnine measuring 11.5 <i>µ</i>g/g (±0.91). This finding raised the possibility that the catatonia produced by bulbocapnine is the consequence of an elevation in the striatal levels of Ach and accompanying physiological events in the striatal system. The catatonia produced by the various manipulations described could be reversed by the injection of 80–100 mg <i>L</i>-dopa in solution, i.p. and sometimes locomotor activity was even greater than that observed in the control period.

Modification of escape from noxious stimuli after bulbar reticular formation lesions

Quantitative behavioral tests showed that unilateral bulbar lesions made in anesthetized cats, damaging nucleus gigantocellularis (NGc), nucleus paragigantocellularis dorsalis (Pgd), and/or the magnocellular tegmental field (FTM), increased latency and threshold voltage for escape from electric shock to the feet. Motor function, visual orientation, and orientation to sound were normal. It is hypothesized that NGc, Pgd, and FTM may constitute a functional complex, operating such that adequate unilateral damage to this field significantly disrupts input into the midline thalamic area.

Endormement vago-aortique après section sagittale médiane du tronc cérébral et après administration de p-chlorophénylalanine, ou destruction des noyaux du raphé

Vago-aortic sleep after midsagittal section of the brain stem and administration of p-chlorophenylalanine, or after destruction of the raphe nuclei Vago-aortic sleep (cortical synchronization and myosis) triggered by vago-aortic stimulation has been tested in the ‘encèphale isolé’ (EI) cat before and after midsagittal section of the brain stem or suppression of the tryptaminergic mechanisms of the raphe nuclei. A midsagittal section, extending from the caudal bulbar area to the caudal mesencephalic level, does not prevent either the myosis or the cortical synchronizations triggered by the vago-aortic stimulation: the synchronizing pathway does not cross the midline until at least the caudal mesencephalic level and does not directly imply the nuclei obscurus, pallidus, magnus and pontis of the raphe. The tryptaminergic system inactivation was performed (in acute as well as in chronic cat) by electrolytic lesions localized at the level of the brain stem serotonophoric somas, or by the use of p-chlorophenylalanine (PCPA), or by the association of these two methods; in all cases vago-aortic synchronizations occurred; however, they were more or less easily obtained depending upon the experimental conditions: the tryptaminergic activities are not necessary for the onset of vago-aortic synchronization. The lower the level of reticular activity (hypocapnia, minute doses of Nembutal, reticular lesions), the easier it was to obtain vago-aortic synchronizations in animals with raphe system destroyed and pretreated with PCPA. The raphe nuclei could inhibit the waking system; this hypothesis is discussed.

Brain stem pathways, cortical modulation, and habituation of the acoustic startle response

Rats with bilateral lesions in the inferior colliculi, superior colliculi, anterior (mesencephalic) reticular formation, or posterior (pontine) reticular formation, in addition to sham-operated animals, were studied to determine the effects of damage to these sites on short-term (within sessions) or long-term (across days) habituation of the acoustic startle response. Lesions placed in posterior reticular formation reduced short-term habituation, while damage to other structures had little effect. Damage to the inferior colliculi, anterior reticular formation, and posterior reticular formation reduced or abolished long-term habituation. In addition, damage to the inferior colliculi abolished the acoustic startle response for 2 to 3 days postoperatively, but full recovery of the response was evident by 4-days postoperative recovery. Startle response amplitude was related to the anterior-posterior placement of reticular formation lesions. More posteriorly placed lesions reduced or abolished the startle response. These results suggest that the reticular formation may underlie short-term habituation of the acoustic startle response and that the normal pathway of this response involves information relayed to reticular formation via the inferior colliculi. However, parallel pathways from lower auditory relay appear to exist since complete recovery of the acoustic startle occurs within 4 days following removal of the inferior colliculi. Rats with lesions in the frontal poles, dorsal hippocampus and overlying parietal cortex, parietal cortex alone, or auditory cortex were studied to determine the effects of damage to these areas on short-term or long-term habituation of the acoustic startle response. With the exception of parietal cortical control lesions, all subjects showed some impairment of long-term habituation following cortical damage. Short-term habituation was unaffected by any of the lesions. The results are compared to previous reports of the effects of damage to cortex and the brain stem.