The role of metalloprotease in pathogenesis of nervous system diseases

Matrix Metalloproteases (MMPs) comprise a big family of proteolytic enzymes secreted into extracellular matrix and involved in remodelling of many tissues. The MMPs' activity is regulated on many levels. It is also determined by specific inhibitors known as tissue inhibitors of metalloproteases (TIMPs). Several studies revealed that MMPs have a role not only in physiological processes but also in pathophysiology of nervous system diseases, such as multiplex sclerosis, Guillan-Barré syndrome and strokes. Concerning demyelination MMPs are responsible for degradation of myelin components and facilitation of immune cells migration into inflammatory sites by degrading vascular basement membrane. We still investigate substances with positive clinical effect on the nervous system diseases due to MMPs inactivation.     

Pseudochoreoathetosis as manifestation of cervical cord lesion. Case report

The involuntary movements of choreoathetotic type are commonly regarded as a sign of basal ganglia lesion. However, such movements can also occur in pathological processes involving the cervical spinal cord. This condition is referred to as pseudochoreoathetosis. Involuntary movements can be related to lack of proper coordination between agonist and antagonist muscles, their simultaneous activation due to impairment of reciprocal inhibition. The characteristic feature of pseudochoreoathetosis is proprioceptive sensory loss. In this paper we present 4 patients who developed various involuntary limb movements in early stage of the disease. Lesions in the cervical spinal cord were confirmed by MRI. In case 1 the cause was astrocytoma, in cases 2 and 3--demyelination, in case 4 the precise character of the lesion could not be established. Pseudochoreoathetosis is a rare condition which often remains unrecognized. The presented cases emphasise the importance of early and correct diagnosis leading to proper therapeutical procedure.     

28-day oral toxicity study with soft corticosteroid BNP-166 in rats and dogs, followed by a 14-day recovery period

The aim of the present study was to evaluate the soft corticosteroid BNP-166 in rats and dogs treated orally with 0.2, 2.0, and 20.0 mg/kg for 28 days and the reversibility of any abnormalities during a 14-day post-dosing period. The test substance, BNP-166, was well tolerated during the 28-day treatment period. The observed changes were all characteristic for the pharmacological actions of a glucocorticoid. Treatment related changes occurred in the adrenals and thymus, and, to a lesser extent, in the lymph nodes, spleen and liver. There were no statistically significant reductions in the cortisol levels of all groups in the 0.2 and 2 mg/kg treatments. Significant reductions were observed in the high-dose group (20 mg/kg), but levels returned to normal by the end of the 14-day recovery period. Based on the results, the No Observable Adverse Effect Level (NOAEL) of BNP-166 soft corticosteroid in rat and dog after 28-day oral administration is 2 mg/kg. This value is approximately 40 times higher than that of budesonide. Pharmacodynamic and receptor binding studies have shown BNP-166 to have a similar potency to budesonide; therefore, BNP-166 can be considered safer when administered orally than other corticosteroids such as prednisolone or budesonide.     

Rapid down-regulation of GABA-A receptors after pretreatment of mice with progesterone

The effect of a single administration of a high dose of progesterone on brain [3H]muscimol binding, was examined in mice using quantitative autoradiography. It was found that progesterone given at the dose of 150 mg/kg ip (the ED85 dose established previously in the model of picrotoxin seizures, Cz?onkowska et al., Pharmacol. Biochem. Behav., 2000, 67, 345-353), significantly decreased the specific binding of [3H]muscimol to the nucleus caudatus and nucleus accumbens, as early as 1 h after injection. A similar tendency, close to the statistically significant level, was also present in the dentate gyrus of the hippocampus (p = 0.07). It is suggested that a high dose of progesterone and ensuing excessive stimulation of GABAA receptors by its metabolites, neurosteroids, could bring about rapid changes in the GABAA receptor number and/or affinity.     

Left-hand somatosensory stimulation combined with visual scanning training in rehabilitation for post-stroke hemineglect: A randomised,double-blind study

The aim of this randomised, double-blind study was to investigate the therapeutic effectiveness of left-hand electrical stimulation for patients with post-stroke left visuo-spatial neglect. This approach was hypothesised to enhance activation of the right hemisphere attention system and to improve visual exploration of extrapersonal space. Participants (n = 40) in the study were in a relatively early stage of recovery from their first right hemisphere stroke, and were randomly assigned to the experimental (E) or control (C) group. Group E received conventional visual scanning training combined with electrostimulation of the left hand, while Group C received scanning training with sham stimulation. Their visuo-spatial neglect was assessed twice, prior to the rehabilitation programme and on its completion, using cancellation tests and a letter-reading task. The effect of electrostimulation on hemineglect was assessed following a single administration and after a month-long rehabilitation programme.

Although the immediate effect of stimulation was poor, after a month-long rehabilitation period we found significantly greater improvement in Group E patients than in Group C patients. Interestingly, the presence of hemisensory loss did not weaken the observed effect. Therefore, we claim that contralesional hand stimulation combined with visual scanning was a more effective treatment for hemineglect rehabilitation than scanning training alone.     

Does brain degeneration in Wilson disease involve not only copper but also iron accumulation?

Background and purposeWilson disease (WD) is an autosomal recessive inherited disorder of hepatic copper metabolism. Clinical manifestations of WD include neurologic, hepatic and psychiatric symptoms. Most WD patients with the neuropsychiatric form, and some with the hepatic and presymptomatic forms have both hypointense and hyperintense lesions in basal ganglia on T2-weighted magnetic resonance imaging (MRI), which can be iron and copper accumulation. It has been established that T2* and susceptibility-weighted imaging (SWI) are highly sensitive in demonstrating brain iron accumulation, showing decreased signal intensity. Hypointense globus pallidus (GP) signal has been described on T2-, T2*-weighted images and on SWI as typical MRI lesion for patients with neurodegeneration with brain iron accumulation (NBIA). We investigated whether WD patients have MRI changes suggesting iron accumulation using T2*-weighted and VEN_BOLD SWI imaging protocols.Material and methodsStandard MRI with additional sequences (T2*-weighted and VEN_BOLD SWI) was performed in consecutively admitted, clinically stable, and treated patients.ResultsTwenty-eight patients entered the study. Hypointensity in the GP was observed on T2*-weighted images in 10 patients. Using the VEN_BOLD SWI technique, we found hypointense signal in GP in 20 patients.ConclusionsMRI data suggest not only copper but also iron accumulation in GP in WD patients.