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.

Protective effect of a new hypothalamic peptide against cobra venom and trauma-induced neuronal injury.

A study of separate and combined actions of cobra venom (CV) and a new hypothalamic proline-rich polypeptide (PRP) isolated from magnocellular cells (NPV and NSO) on intoxication- and trauma-induced neuronal injury (during 3-4 weeks after hemisection with and without PRP treatment) was carried out. The registration of background and evoked impulse activity flow, changes in spinal cord (SC) inter- and motoneurons, responding to flexor, extensor, and mixed nerve stimulation in both acute and chronic experimental neurodegeneration was performed. The facilitating effect of PRP on the abovementioned neurons was revealed. High doses of CV that evoked the neurodegenerative changes demonstrated an inhibitory effect. In this case PRP treatment both before and after intoxication restored electrical neuronal activity to baseline level and higher. These results are evidence of protective action of PRP. The low doses of CV induced a facilitating effect. The combination of CV and PRP displayed an additive facilitating effect; in a number of cases the repeated administration of CV led to decrease of significant PRP effect till baseline level (for example, the inhibition after primary response prior to secondary late discharge). Greater liability of the secondary early and late long-time discharges of poststimulus responses, differently expressed in various neuron types of SC to chemical influences is of interest. PRP-induced inhibition of the paroxysmal activity related with CV action is also very interesting. Morpho-functional experiments with SC injury demonstrated the abolition of difference in the background and evoked SC neuronal activity below the section and on intact symmetric side after daily PRP administration for 3 weeks. PRP hindered the scar formation and activated neuroglia proliferation; it promoted white matter element growth, hampered the degeneration of cellular elements, and protected against tissue stress. Our results favor the combined use of PRP and CV in clinical practice for the treatment of neurodegeneration of toxic and traumatic origin, as well as specific neurodegenerative diseases such as Alzheimer's.

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.

Immunohistochemical study of immunophilin 1-15 fragment in intact frog brain, and in the brain and spinal cord of intact and spinal cord hemisectioned rats.

Previously by immunohistochemical technique the distribution of immunophilin 1-15 fragment (IphF) isolated from bovine hypothalamus was examined in various tissues (heart, lung), including immune system organs (spleen and thymus) of intact rats. IphF-like immunoreactivity (IphF-LI) was revealed in several cell types: lymphocytes, monocytes, macrophages and mast cells. In the present study the immunohistochemical localization of IphF was examined in intact rat and frog brains. In rat brain several cell groups concentrated particularly in the supraoptic nucleus (SON) of hypothalamus, medulla oblongata (reticular formation, olives, hypoglossal and facial motor nuclei) and cerebellum (lateral cerebellar nucleus) demonstrated IphF-LI. In frog hypothalamus (SON) the same working dilution (1:5000) of IphF-antiserum revealed very strong immunoreactivity. In the paraventricular nucleus (PVN) IphF-LI varicosities were scattered around the immunonegative cells. The second cell groups showing IphF-LI in the frog brain were gliocytes (mainly the astrocytes). Besides, IphF distribution was investigated in rats subjected to hemisection of spinal cord (SC) with and without administration of proline-rich polypeptide (PRP). PRP was isolated from bovine neurohypophysis neurosecretory granules, produced by magnocellular nuclei of hypothalamus. Hemisection of SC led to changes of IphF distribution in the hypothalamus. In PRP treated animals IphF showed no immunoreactivity. PRP is suggested to act as a neurotransmitter and neuroregulator.

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.