[Spasticity: from pathophysiology to treatment]. / Spastichnost': ot patofiziologii k lecheniiu.

The article presents modern views on the pathophysiology of spasticity, which is a frequent disabling consequence to the upper motor neuron (UMN) damage. Morphological and functional system of motion organization and the changes after the UMN damage is considered. The authors analyze existing definitions of spasticity. Stages of spasticity development are described in the context of neuroplasticity as well as in the framework of pathogenesis and sanogenesis. Existing ideas of its pathogenesis are compared with the typical clinical symptoms. The occurring pathological processes in muscles, tendons and joints that can aggravate the development of spasticity and complicate the diagnosis are considered. In addition, the main pathological spasticity patterns are described and the current development of diagnostic techniques is estimated. A review of main methods of spasticity treatment is presented. Special attention is paid to the botulinum neurotoxin type A (BoNT) preparations and central action muscle relaxants. The pathophysiological basement for complex treatment of spasticity as a part of the general rehabilitation process is given, so that the BoNT can be considered as the obligatory element of standard rehabilitation programs.

Focal Transplantation of Aberrant Glial Cells Carrying the SOD1G93A Mutation into Rat Spinal Cord Induces Extensive Gliosis.

OBJECTIVE: We aimed to determine the potential of aberrant glial cells (AbAs) isolated from the spinal cord of adult SOD1G93A symptomatic rats to induce gliosis and neuronal damage following focal transplantation into the lumbar spinal cord of wild-type rats. METHODS: AbAs were obtained from the spinal cords of SOD1G93A symptomatic rats. One hundred thousand cells were injected using a glass micropipette into the lumbar spinal cords (L3-L5) of syngeneic wild-type adult rats. Equal volumes of culture medium or wild-type neonatal microglia were used as controls. Seven days after transplantation, immunohistochemistry analysis was carried out using astrocytic and microglia cell markers. Transplanted SOD1G93A AbAs were recognized by specific antibodies to human SOD1 (hSOD1) or misfolded human SOD1. RESULTS: Seven days after transplantation, AbAs were mainly detected in the medial region of the lumbar ventral horn as a well-limited cell cluster formed at the site of injection by their immunoreactivity to either misfolded SOD1 or normally folded hSOD1. Compared with controls, transplanted AbAs were surrounded by marked microgliosis and reactive astrocytes. Marked microgliosis was observed to extend bilaterally up to the cervical cord. Motor neurons close to AbA transplants were surrounded by activated glial cells and displayed ubiquitin aggregation. CONCLUSIONS: AbAs bearing mutant SOD1G93A have the potential to induce neuroinflammation along the spinal cord and incipient damage to the motor neurons. The emergence of AbAs during amyotrophic lateral sclerosis pathogenesis may therefore be a mechanism to boost neuroinflammation and spread motor neuron damage along the neuroaxis.

Effects of metal exposure on motor neuron development, neuromasts and the escape response of zebrafish embryos.

Low level metal contaminations are a prevalent issue with often unknown consequences for health and the environment. Effect-based, multifactorial test systems with zebrafish embryos to assess in particular developmental toxicity are beneficial but rarely used in this context. We therefore exposed wild-type embryos to the metals copper (CuSO4), cadmium (CdCl2) and cobalt (CoSO4) for 72 h to determine lethal as well as sublethal morphological effects. Motor neuron damage was investigated by immunofluorescence staining of primary motor neurons (PMNs) and secondary motor neurons (SMNs). In vivo stainings using the vital dye DASPEI were used to quantify neuromast development and damage. The consequences of metal toxicity were also assessed functionally, by testing fish behavior following tactile stimulation. The median effective concentration (EC50) values for morphological effects 72 h post fertilization (hpf) were 14.6 mg/L for cadmium and 0.018 mg/L for copper, whereas embryos exposed up to 45.8 mg/L cobalt showed no morphological effects. All three metals caused a concentration-dependent reduction in the numbers of normal PMNs and SMNs, and in the fluorescence intensity of neuromasts. The results for motor neuron damage and behavior were coincident for all three metals. Even the lowest metal concentrations (cadmium 2mg/L, copper 0.01 mg/L and cobalt 0.8 mg/L) resulted in neuromast damage. The results demonstrate that the neuromast cells were more sensitive to metal exposure than morphological traits or the response to tactile stimulation and motor neuron damage.