The differential contributions of the parvocellular and the magnocellular subdivisions of the red nucleus to skilled reaching in the rat.

During the execution of the skilled reaching task, naïve rats bring their elbow to the midline of their body to aim at the food target, perform the arpeggio movement to grasp it and supinate the paw to bring the food to their mouth. Red nucleus lesions in the rat interfere with each of these three movement elements of reaching. On the other hand, lesions to the rubrospinal tract, which originate from the magnocellular subdivision of the red nucleus, only interfere with the arpeggio movement. This latter evidence strongly suggests that impairment in aiming and supinating could be under the control of the parvocellular subdivision of the red nucleus. In order to test this hypothesis, rats were trained on the skilled reaching task and then received either complete lesions of the red nucleus or lesions restricted to its parvo- or magnocellular subdivision. In line with previous data, complete excitotoxic lesions of the red nucleus compromised limb aiming, arpeggio and supination. Lesions restricted to the parvocellular division of the red nucleus abolish supination and interfere with aiming, although the latter result did not reach significance. The results are discussed in terms of the distinct connectivity and functional significance of these two architectonic subdivisions of the red nucleus.

The diagnosis and surgical treatment of central brain herniations caused by traumatic bifrontal contusions.

The objective of this study was to investigate the diagnosis and surgical treatment of central brain herniations caused by traumatic bifrontal contusions. A total of 63 patients (45 men and 18 women; mean age of 43 years with a range from 20 to 72 years) who suffered from traumatic bifrontal contusions between January 2007 and December 2012 were inspected. The clinical and imaging results were studied for all patients, and we found that swelling of the mesencephalon and a downward shift of the bilateral red nucleus were significant signs of central brain herniation in the image of magnetic resonance imaging. All patients were given a simultaneous bilateral craniotomy for balanced decompressive surgery. The Glasgow Outcome Scale was used to monitor the patients during the follow-up period, which lasted from 6 to 52 months with a mean of 22 months. At the termination of the follow-up period, the following Glasgow Outcome Scale scores were obtained: 14 patients scored 5 points, 22 patients scored 4 points, 7 patients scored 3 points, 13 patients scored 2 points, and 7 patients scored 1 point. Therefore, our study suggested that an early magnetic resonance imaging scan could result in a more timely diagnosis of central brain herniation, and simultaneous bilateral craniotomy was found to be one of the best treatments for central brain herniation to improve patient outcomes.

Role of the lateral reticular nucleus in suppressing the jaw-opening reflex following stimulation of the red nucleus.

We found in a previous study that stimulation of the red nucleus (RN) facilitated the low-threshold afferent-evoked jaw-opening reflex (JOR) and suppressed the high-threshold afferent-evoked JOR. It has been reported that the RN projections to the contralateral lateral reticular nucleus (LRt), and stimulation of the LRt inhibits the nociceptive JOR. These facts suggest that RN-induced modulation of the JOR is mediated via the LRt. We investigated whether electrically induced lesions of the LRt, or microinjection of muscimol into the LRt, affects RN-induced modulation of the JOR. The JOR was evoked by electrical stimulation of the inferior alveolar nerve (IAN), and was recorded as the electromyographic response of the anterior belly of the digastric muscle. The stimulus intensity was either 1.2 (low-threshold) or 4.0 (high-threshold) times the threshold. Electrically induced lesion of the LRt and microinjection of muscimol into the LRt reduced the RN-induced suppression of the high-threshold afferent-evoked JOR, but did not affect the RN-induced facilitation of the low-threshold afferent-evoked JOR. These results suggest that the RN-induced suppression of the high-threshold afferent-evoked JOR is mediated by a relay in the contralateral LRt.

Posttraumatic Benedikt's syndrome: a rare entity with unclear anatomopathological correlations.

BACKGROUND: This study sought to present a very rare case of a posttraumatic midbrain lesion producing a debilitating constellation of symptoms identified as Benedikt's syndrome. METHODS: A 20-year-old woman with traumatic brain injury presented with ipsilateral internal and external ophthalmoplegia, and contralateral hemiataxia, proprioception disturbances, hypertonicity, slight hemiparesis, and hyperactive tendon reflexes. A bibliographic search was performed in PubMed. RESULTS: Neuroimaging revealed a left midbrain lesion at the level of the superior colliculi. In the literature, virtually all Benedikt's syndrome cases, which are rare anyway, are due to midbrain infarcts (basilar or posterior cerebral artery branches). There is only one case from 1963, reported as a posttraumatic Benedikt-type dyskinesia (French language). The historical evolution of the anatomopathologic correlations of the syndrome is also discussed. CONCLUSIONS: Benedikt's syndrome is a very rare condition, usually of vascular etiology. Our case is just the second one of traumatic pathogenesis ever reported, the first in the English language literature.

Impaired arpeggio movement in skilled reaching by rubrospinal tract lesions in the rat: a behavioral/anatomical fractionation.

Spinal cord injury damaging the rubrospinal tract (RST) interferes with skilled forelimb movement, but identification of the precise role of the RST in this behavior is impeded by the difficulty of surgically isolating the RST from other pathways running within the lateral funiculus (LF). The present study used a skilled reaching task and a behavioral/anatomical dissection method to identify the contribution of the RST to skilled forelimb movement. Rats were trained on the skilled reaching task and subjected to lesions of the LF. Based on histological evaluation, the animals were assigned to large, medium, or small LF lesion size groups. End point and arm/hand/digit movements were subsequently identified for each group. Success was impaired in all groups, but the impairment was not related to lesion size. Frame-by-frame qualitative analysis of the video recordings revealed that large LF lesions abolished the elements of digits close, digits open, arpeggio, grasp, supination 2, and release. Medium LF lesions interfered with a subset of the movement elements that were shown to be affected by the large LF lesions, namely arpeggio and grasp. Only the arpeggio movement was compromised after small LF lesions. The results show that not only does the LF contribute to skilled reaching, but because the RST was likely to have been damaged in all lesion groups, the RST is more involved in hand rotation than in digit use. The results are discussed in relation to the fiber tracts that are likely to be damaged in the different LF lesion groups.

Dystonia associated with pontomesencephalic lesions.

Secondary dystonia is well known subsequent to lesions of the basal ganglia or the thalamus. There is evidence that brainstem lesions may also be associated with dystonia, but little is known about pathoanatomical correlations. Here, we report on a series of four patients with acquired dystonia following brainstem lesions. There were no basal ganglia or thalamic lesions. Three patients suffered tegmental pontomesencephalic hemorrhage and one patient diffuse axonal injury secondary to severe craniocerebral trauma. Dystonia developed with a delay of 1 to 14 months, at a mean delay of 6 months. The patients' mean age at onset was 33 years (range 4-56 years). All patients presented with hemidystonia combined with cervical dystonia, and two patients had craniofacial dystonia in addition. Three patients had postural or kinetic tremors. Dystonia was persistent in three patients, and improved gradually in one. There was little response to medical treatment. One patient with hemidystonia combined with cervical dystonia improved after thalamotomy. Overall, the phenomenology of secondary dystonia due to pontomesencephalic lesions is similar to that caused by basal ganglia or thalamic lesions. Structures involved include the pontomesencephalic tegmentum and the superior cerebellar peduncles. Such lesions are often associated with fatal outcome. While delayed occurrence of severe brainstem dystonia appears to be rare, it is possible that mild manifestations of dystonia might be ignored or not be emphasized in the presence of other disabling deficits.

Changes in cortically induced rhythmic jaw movements after lesioning of the red nucleus in rats.

We study whether the red nucleus (RN) lesion can modify rhythmic jaw movements. Rhythmic jaw movements were induced by repetitive electrical stimulation of the two cortical masticatory areas (area A: the orofacial motor cortex; area P: the insular cortex). Lesions made by applied electric current in the RN were found to influence the rhythmic jaw movements induced by stimulation of A-area. The distance between the maximum and minimum jaw-opening positions was less after the lesions were induced. The duration of rhythmic jaw movements was shorter after lesioning. In contrast, lesions of the RN did not influence rhythmic jaw movements induced by stimulation of the P-area. Next, kainic acid (0.2 microl, lesion group) or phosphate-buffered saline (0.2 microl, control group) was injected into the left RN. Three days after injection, rhythmic jaw movements were induced by repetitive electrical stimulation of the A-area. The distance between the maximum and minimum jaw-opening positions in the lesion group was smaller than in the control group. The rhythmic jaw movements of the lesion group had shorter duration than the control group. These results suggest that the RN is involved in the modification of jaw movements induced by stimulation of the A-area.

Profound differences in spontaneous long-term functional recovery after defined spinal tract lesions in the rat.

The purpose of this study was to compare spontaneous functional recovery after different spinal motor tract lesions in the rat spinal cord using three methods of analysis, the BBB, the rope test, and the CatWalk. We transected the dorsal corticospinal tract (CSTx) or the rubrospinal tract (RSTx) or the complete dorsal half of the spinal cord (Hx) at thoracic level T8. Functional recovery was monitored for 31 weeks. We found no recovery of consistent inter limb coordination in any experimental group over time using the BBB locomotor rating scale. Quantitative CatWalk analysis revealed significant differences between experimental groups for inter limb coordination (RI). RSTx and Hx animals showed a significant decrease in the RI, and only in the RSTx group did the RI improve from 6 weeks post-lesion onward. Significant differences between experimental groups in step sequence patterns and base of support were also observed. In the rope test all experimental groups had significantly higher error percentages compared to control animals. Tracing of the CST revealed enhanced collateral formation rostral to the lesion in the CSTx group, not in other groups. The results presented here show that locomotor function in all, but CSTx groups gradually improved over time. This is important for studies that employ pharmacological, cell-, and/or gene therapy- based interventions to improve axonal regeneration and functional recovery after spinal cord injury.

Close axonal injury of rubrospinal neurons induced transient perineuronal astrocytic and microglial reaction that coincided with their massive degeneration.

To learn more about the pathophysiology of axonal injury and the significance of axon collaterals on the survival of axotomized cord-projection central neurons, we studied the survival rate, surrounding astrocytic and microglial reactions, and bouton coverage on rat rubrospinal cell bodies following their axonal lesion at the brain stem and upper cervical level. The brain stem lesion disconnected most rubrospinal neurons from all their targets, while the upper cervical lesion spared their supraspinal collaterals. Much higher cell loss accompanied by robust astrocytic and microglial reaction was found following brain stem than upper cervical lesion starting 4 days postaxotomy. The reaction of astrocytes had subsided while microglial reaction remained relatively robust by 10 weeks postaxotomy when the cell loss had slowed down. Ultrastructural observation revealed that reactive astrocytes covered 40%, an increase from the 20% of control, of brain stem-axotomized rubrospinal cell body surface at 4 days and 2 weeks and returned to normal levels by 10 weeks postlesion. An increase of apposition by axons and dendrites and a moderate decrease of round and flattened vesicle-containing bouton contacts at 4 days and 2 weeks and returning to normal levels at 10 weeks postaxotomy accompanied this. It appears that although axotomy induced robust astrocytic reaction around cord-projection central neurons, this, unlike their periphery-projection counterparts, failed to effectively strip their somatic synapses. In effect, this might in part determine neuronal fate following axonal injury.

Comparison of the effects of electrolytic and chemical destruction of the red nucleus on the compensatory capacity of rats with rubrospinal tract lesions.

Transection of the rubrospinal tract in rats, performed before lesion of the red nucleus, resulted in the facilitated recovery of motor activity and operantly conditioned reflexes. Such facilitation was absent when the red nucleus is lesioned alone. This phenomenon is explained by the switching of descending influences on the corticospinal tract through the participation of the following system: red nucleus--inferior olive--cerebellum--ventrolateral thalamic nucleus--cerebral cortex. The above mentioned facilitating influence on the recovery process was particularly prominent in rats with quinolinic acid-induced lesion of the red nucleus. Under these conditions, the cerebellar ascending fibers to the ventrolateral thalamic nucleus were preserved. Decreased facilitated recovery following electrolytic lesion of the red nucleus suggests the existence of additional cerebello-cortical pathways for the realization of the switching phenomenon.

Neural tissue transplants rescue axotomized rubrospinal cells from retrograde death.

Rubrospinal tract cells undergo massive retrograde degeneration following spinal cord damage in newborn rats (Prendergast and Stelzner, J. Comp. Neurol. 166:163-172, '76b). In the current study, fetal spinal cord tissue (E12-14) was grafted into midthoracic spinal cord lesions in newborn rats (less than 72 hours old) in order to determine whether such transplants could modify the response of the immature host central nervous system (CNS) to axotomy. These transplants grew, differentiated, and formed extensive areas of apposition with the recipient spinal cords. Counts of red nucleus (RN) neurons indicated a significant loss of RN neurons in animals with lesion alone, but a rescuing of most of these cells if a transplant was placed into the lesion site. In fact, the number of neurons in animals with lesions and transplants was not significantly different from control animals. Horseradish peroxidase injected 10-15 mm caudal to the transplant (at 1-12 months post-transplantation) labeled neurons within the transplant and RN neurons contralateral to the spinal cord lesions and transplant. In animals with spinal cord lesion but no transplant, only the unaxotomized RN was labeled. Thus, spinal cord transplants prevented the massive retrograde cell death of immature axotomized rubrospinal neurons. Some of these rescued neurons projected to the host spinal cord caudal to the transplant.