Effects of bacterial melanin on movement, posture, and skilled balancing deficits after unilateral destruction of substantia nigra pars compacta in rats.

Sixteen adult male rats were initially trained to an instrumental conditioned reflex (ICR) and subjected to unilateral destruction of substantia nigra pars compacta. Part of the animals was injected with bacterial melanin solution on the next day of destruction. The other 8 rats served as the control group. Recovery rates for ICR and dynamics of paralyzed hindlimb movements were studied in both groups. Conditioned reflex and contralateral to lesion hindlimb movements recovered faster in rats injected with bacterial melanin after the destruction.

Effects of bacterial melanin on motor recovery and regeneration after unilateral destruction of Substantia Nigra pars compacta in rats.

We examined the potential neuroprotective action of bacterial melanin (BM) in rats after unilateral destruction of Substantia Nigra pars compacta (SNc) dopaminergic neurons. 24 rats were initially trained to an instrumental conditioned reflex (ICR) and then subjected to unilateral electrolytic destruction of SNc. Unilateral deficit in balancing hindlimb movements was observed in all rats after the destruction. On the next day after the destruction part of the animals (n=12) was intramuscularly injected with BM solution at the concentration 6 mg/ml (0.17 g/kg). The other 12 operated rats served as a control group. On the second day after the operation the testing of instrumental conditioned reflex was resumed in both groups. Comparison of recovery periods for the ICR in both groups showed that recovery of the reflex and balancing hindlimb movements in melanin treated rats took place in three postoperative testing days, whereas in control group the recovery was not complete after 23 testing days. Electrophysiological study was conducted in 12 intact rats to show the effects of BM on the activity of SNc neurons. The firing rate of neurons was significantly increased by the BM injection. Morpho-histochemical study of brain sections was conducted after the completion of behavioral experiments. In melanin injected rats the study revealed absence of destruction or electrode trace in Substantia Nigra pars compacta of melanin injected rats. BM stimulates regeneration and microcirculation in SNc. Increased electrical activity of SN neurons and regenerative efforts induced by BM accelerate motor recovery after unilateral SNc destruction.

Effects of BT-melanin on recovery of operant conditioned reflexes in rats after ablation of the sensorimotor cortex.

An increase in corticofugal plasticity was demonstrated in adult rats after unilateral ablation of the sensorimotor cortex accompanied by intramuscular administration of low concentrations of BT-melanin solution. The result was acceleration of the process of compensatory recovery in the central nervous system, this being supported by the rapid recovery of a previously acquired operant conditioned reflex and movement of the paralyzed limb as compared with control animals. It is suggested that compensation of the motor deficit arising after ablation of the sensorimotor cortex is mediated by the ability of the two major motor systems of the brain - the corticospinal and the corticorubrospinal - to exhibit mutual substitution of their functions. This phenomenon of the functional switching of descending influences also occurred in rats of the control group not exposed to BT-melanin. However, the difference between the recovery times of the operant conditioned reflex and limb movement in the control and experimental groups provided evidence of an apparent acceleration in these processes as a result of BT-melanin. These results suggest that low concentrations of BT-melanin may have applied uses.

Dynamics of changes in operant reflexes in rats after transection of the corticospinal tract and removal of the sensorimotor region of the cerebral cortex.

Prior unilateral transection of the bulbar pyramid facilitated recovery of operant reflexes and compensatory processes occurring after removal of the ipsilateral sensorimotor cortex in rats. This increase in corticofugal plasticity was absent when only the sensorimotor cortex was removed. This phenomenon is explained by switching of descending influences to the corticorubrospinal system via the following loop: corticobulbar projection--red nucleus--lower olive--cerebellum--thalamus--cortex. A general property of this phenomenon is that prior lesioning of the peripheral part of the descending spinal projection acquires anticipatory signal value for mobilizing the compensatory abilities of the brain with the aim of recovering from the deficit of the central branch of the system.

The role of the ventrolateral nucleus of the thalamus in the switching of descending influences to motor activity in the rat.

Studies on rats showed that the facilitating influence of preliminary transection of the rubrospinal tract on recovery of motor activity and operant reflexes disrupted by lesioning of the red nucleus was more apparent when lesioning was chemical than when lesioning was electrolytic. This is due to the survival of cerebellothalamic fibers to the ventrolateral nucleus of the thalamus after chemical lesioning of the red nucleus with quinolinic acid. It was also shown that preliminary lesioning of the ventrolateral thalamic nucleus strongly hindered the switching of motor activity under the control of the corticospinal tract in rats subjected to section of the rubrospinal tract and lesioning of the red nucleus.

Time-dependent effects of pyramidotomy in the operantly conditioned rats.

The effect of unilateral transection of bulbar pyramid on operantly conditioning in rats, have been shown to be in direct relationship with the time of its execution. Stable instrumental reflexes reappeared on average 3.9 days after the transection of the bulbar pyramid. However, preliminary transection of the pyramid led to the prolongation of stabilization of operant conditioning after an average of 16.5 days. These findings are considered to be in view of the mechanisms of switching of descending influences of corticospinal and cortico--rubrospinal systems.

The role of some brain structures in the switching of the descending influences in operantly conditioned rats.

A hypothesis was proposed according to which the switching of descending influences by the corticospinal and corticorubrospinal systems was associated with rubro-olivary projection involvement depending on the context of movement [Kennedy P. R. (1990) Trends Neurosci. 13, 474-479]. Our results confirmed and extended this hypothesis. It was shown that a preliminary transection of the dorsolateral funiculus (containing the rubrospinal tract) accelerated the compensatory rehabilitation process following lesions of the red nucleus and the ventrolateral thalamic nucleus in albino rats with learned instrumental reflexes on equilibrium. A preliminary lesion of the ventrolateral thalamic nucleus considerably hampered the switching process; nevertheless, performance of the reflexes suggested that the switching of cerebellar ascending influences to the cerebral cortex could be completed through other cerebellocortical pathways as well. Comparison of the results of electrolytic and chemical lesions of the red nucleus suggested a similar conclusion. It was established that the conditioning and recovery of already learned instrumental reflexes were impossible after complete neurotoxic destruction of the inferior olive. The data obtained emphasize the role of the inferior olive, ventrolateral thalamic nucleus and red nucleus in the switching of descending influences in operantly motor conditioned rats. Motor deficit and the compensatory rehabilitation process depended on the severity of inferior olive destruction combined with a high transection of the dorsolateral funiculus and a destroyed red nucleus. Long-lasting training improved compensation of motor deficit and stabilized instrumental reflexes to some extent in rats with incomplete destruction of the inferior olive. It has been suggested that these modifications occur because of collateral sprouting in the olivocerebellar system.

Enhanced behavioral recovery from sensorimotor cortex lesions after pyramidotomy in adult rats.

Unilateral transection of the bulbar pyramid, performed before the ablation of the ipsilateral sensorimotor cortex, has been shown to facilitate the recovery of operantly conditioned reflexes and compensatory processes in rats. Such enhanced behavioral recovery was absent when only the sensorimotor cortex was ablated. This phenomenon is explained by the switching of motor activity under the control of the cortico-rubrospinal system. Switching of the descending influences is accomplished through the following loop: cortico-rubral projection-red nucleus-inferior olive-cerebellum-thalamus-cerebral cortex. This suggests that a preliminary lesion of the peripheral part of the system, represented by a descending spinal projection, facilitates the recovery processes to develop during the subsequent destruction of its central part.

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.