Matrix metalloproteinases and their inhibitors in human traumatic spinal cord injury.

in BMC Neurology (2007), 7

BACKGROUND: Matrix metalloproteinases (MMPs) are a family of extracellular endopeptidases that degrade the extracellular matrix and other extracellular proteins. Studies in experimental animals ... [more ▼]

BACKGROUND: Matrix metalloproteinases (MMPs) are a family of extracellular endopeptidases that degrade the extracellular matrix and other extracellular proteins. Studies in experimental animals demonstrate that MMPs play a number of roles in the detrimental as well as in the beneficial events after spinal cord injury (SCI). In the present correlative investigation, the expression pattern of several MMPs and their inhibitors has been investigated in the human spinal cord. METHODS: An immunohistochemical investigation in post mortem samples of control and lesioned human spinal cords was performed. All patients with traumatic SCI had been clinically diagnosed as having "complete" injuries and presented lesions of the maceration type. RESULTS: In the unlesioned human spinal cord, MMP and TIMP immunoreactivity was scarce. After traumatic SCI, a lesion-induced bi-phasic pattern of raised MMP-1 levels could be found with an early up-regulation in macrophages within the lesion epicentre and a later induction in peri-lesional activated astrocytes. There was an early and brief induction of MMP-2 at the lesion core in macrophages. MMP-9 and -12 expression peaked at 24 days after injury and both molecules were mostly expressed in macrophages at the lesion epicentre. Whereas MMP-9 levels rose progressively from 1 week to 3 weeks, there was an isolated peak of MMP-12 expression at 24 days. The post-traumatic distribution of the MMP inhibitors TIMP-1, -2 and -3 was limited. Only occasional TIMP immuno-positive macrophages could be detected at short survival times. The only clear induction was detected for TIMP-3 at survival times of 8 months and 1 year in peri-lesional activated astrocytes. CONCLUSION: The involvement of MMP-1, -2, -9 and -12 has been demonstrated in the post-traumatic events after human SCI. With an expression pattern corresponding largely to prior experimental studies, they were mainly expressed during the first weeks after injury and were most likely involved in the destructive inflammatory events of protein breakdown and phagocytosis carried out by infiltrating neutrophils and macrophages, as well as being involved in enhanced permeability of the blood spinal cord barrier. Similar to animal investigations, the strong induction of MMPs was not accompanied by an expression of their inhibitors, allowing these proteins to exert their effects in the lesioned spinal cord. [less ▲]

Cost estimates of brain disorders in Belgium

in Acta Neurologica Belgica (2006), 106(4), 208-214

This article presents the data on cost of the major brain disorders in Belgium which were retrieved from "Cost of Disorders of the Brain in Europe" study sponsored by the European Brain Council and ... [more ▼]

This article presents the data on cost of the major brain disorders in Belgium which were retrieved from "Cost of Disorders of the Brain in Europe" study sponsored by the European Brain Council and performed by Stockholm Health Economics. The disorders selected were : addiction, depression, anxiety disorders, brain tumours, dementia, epilepsy, migraine and other headaches, multiple sclerosis, Parkinson's disease, psychotic disorders, stroke and trauma. Figures for prevalence of disorders and direct medical, direct non-medical and indirect costs are based on data coming from available electronic data bases, or when missing for Belgium, best possible estimates or extrapolated data were used. All economic data were transformed to E's for 2004 and adjusted for purchasing power parity (PPP). The results show that the total number of people with any brain disorder in Belgium amounts to 2,9 million in 2004, the most prevalent being anxiety disorders 1.1 million, migraine 860 000, addiction (any) 800.000 and depression 500.000 cases. The total cost of all included brain disorders in Belgium was estimated at 10.6 billion Euros. Most costly per case are brain tumours, multiple sclerosis, stroke and dementia. Because of their higher prevalence, however, depression, dementia, addiction, anxiety disorders and migraine have the highest total costs. Taken together, brain disorders consume 4% of the gross national product and cost each citizen of Belgium E 1029 per year The drug costs for brain disorders constitute only 10% of the total drug market in Belgium, and only 4% of the total cost of brain disorders in Belgium. This should be compared to the cost estimates and to a previous study which showed that brain disorders are responsible for 35% of the total burden of all disorders in Europe. This study suggests therefore that the direct healthcare resources, including expenses for drug therapies, allocated to brain disorders in Belgium are not leveled to the indirect costs and burden of these disorders. A comparison with data available from a direct prospective study in demented Belgian patients suggests that the mathematical estimates presented here reflect quite accurately the real average cost for dementia, although there are large variations depending on disease severity. As, in addition, subjects with brain disorders face collateral costs which have not been taken into account and may vary between countries, it seems worthwhile to conduct, in cooperation with patients associations, a complementary survey in the Belgian ecosystem to establish the cost profile of representative patients for the major brain disorders. Such a survey is being organized by a task force of the Belgian Brain Council. [less ▲]

Role of Placental Growth Factor (PLGF) in the inflammatory context resulting from nerve injury, the Wallerian Degeneration.

Poster (2006, November 10)

Long-term depression of trigeminal nociceptive evoked potentials by supraorbital 1Hz electrical stimulations is deficient in migraineurs but not in tension-type headache patients

in Cephalalgia : An International Journal of Headache (2006, November), 26(11), 1386

Towards a definition of intractable headache for use in clinical practice and trials

in Cephalalgia : An International Journal of Headache (2006), 26(9), 1168-1170

Transcranial magnetic stimulation of the visual cortex induces somatotopically organized qualia in blind subjects

in Proceedings of the National Academy of Sciences of the United States of America (2006), 103(35), 13256-13260

After loss of a particular sensory channel, the deprived cortex can be activated by inputs from other sensory modalities. It is not known whether activation of the rewired cortex evokes subjective ... [more ▼]

After loss of a particular sensory channel, the deprived cortex can be activated by inputs from other sensory modalities. It is not known whether activation of the rewired cortex evokes subjective experiences characteristic of that cortex or consistent with the rerouted sensory information. In a previous study, blind subjects were trained to perform visual tasks with a tongue display unit, a sensory substitution device that translates visual displays into electrotactile tongue stimulation. This cross-modal sensory stimulation activated their visual cortices. We now extend this finding by using transcranial magnetic stimulation to examine the perceptual correlates of training-induced plastic responses. We find that blind subjects proficient with the use of the tongue display unit report somatopicaily organized tactile sensations that are referred to the tongue when transcranial magnetic stimulation is applied over the occipital cortex. No such sensations were evoked in trained, blindfolded, seeing control subjects who performed the sensory substitution task equally well. These data show that the perceptual correlate of activity in a given cortical area reflects the characteristics of its novel sensory input source. [less ▲]

Delayed GM-CSF treatment stimulates axonal regeneration and functional recovery in paraplegic rats via an increased BDNF expression by endogenous macrophages

in FASEB Journal (2006), 20(8), 12391241

Macrophages (monocytes/microglia) could play a critical role in central nervous system repair. We have previously found a synchronism between the regression of spontaneous axonal regeneration and the ... [more ▼]

Macrophages (monocytes/microglia) could play a critical role in central nervous system repair. We have previously found a synchronism between the regression of spontaneous axonal regeneration and the deactivation of macrophages 3-4 wk after a compression-injury of rat spinal cord. To explore whether reactivation of endogenous macrophages might be beneficial for spinal cord repair, we have studied the effects of granulocyte-macrophage colony stimulating factor (GM-CSF) in the same paraplegia model and in cell cultures. There was a significant, though transient, improvement of locomotor recovery after a single delayed intraperitoneal injection of 2 mu g GM-CSF, which also increased significantly the expression of Cr3 and brain-derived neurotrophic factor ( BDNF) by macrophages at the lesion site. At longer survival delays, axonal regeneration was significantly enhanced in GMCSF-treated rats. In vitro, BV2 microglial cells expressed higher levels of BDNF in the presence of GM-CSF and neurons cocultured with microglial cells activated by GM-CSF generated more neurites, an effect blocked by a BDNF antibody. These experiments suggest that GM-CSF could be an interesting treatment option for spinal cord injury and that its beneficial effects might be mediated by BDNF.-Bouhy, D., Malgrange, B., Multon, S., Poirrier, A. L., Scholtes, F., Schoenen, J., Franzen, R. Delayed GM-CSF treatment stimulates axonal regeneration and functional recovery in paraplegic rats via an increased BDNF expression by endogenous macrophages. [less ▲]

Les céphalées par abus d'antalgiques et d'anti-migraineux

in Revue Médicale de Liège (2006), 61(4), 217-22

Medication overuse headache (MOH) insidiously evolves from episodic migraine or tension-type headache because of overconsumption of analgesics, ergotamine or triptans. It affects 1-2% of the general ... [more ▼]

Medication overuse headache (MOH) insidiously evolves from episodic migraine or tension-type headache because of overconsumption of analgesics, ergotamine or triptans. It affects 1-2% of the general population, but 15-20% of patients attending specialized headache centers. The precise neurobiologic mechanisms underlying this complication of episodic headaches are not well understood. Abnormalities of central monoaminergic systems have been suggested and substance dependence is more frequent in personal and family histories of affected subjects. In a recent FDG-PET study of 16 migraineurs with MOH before and after analgesics withdrawal we found a persistent hypometabolism of the medial orbitofrontal cortex, comparable to the one described after withdrawal in substance abuse. The orbitofrontal cortex plays a pivotal role in drive, decision-making and drug dependence. We postulate that its hypoactivity predisposes certain migraineurs to MOH and to relapse after withdrawal. There is no unique management strategy for these patients, but medication withdrawal is a prerequisite for the effectiveness of preventive treatments and headache improvement. [less ▲]

Induction of long-lasting changes of visual cortex excitability by five daily sessions of repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers and migraine patients

in Cephalalgia : An International Journal of Headache (2006), 26(2), 143-149

We have shown that in healthy volunteers (HV) one session of 1 Hz repetitive transcranial magnetic stimulation (rTMS) over the visual cortex induces dishabituation of visual evoked potentials (VEPs) on ... [more ▼]

We have shown that in healthy volunteers (HV) one session of 1 Hz repetitive transcranial magnetic stimulation (rTMS) over the visual cortex induces dishabituation of visual evoked potentials (VEPs) on average for 30 min, while in migraineurs one session of 10 Hz rTMS replaces the abnormal VEP potentiation by a normal habituation for 9 min. In the present study, we investigated whether repeated rTMS sessions (1 Hz in eight HV; 10 Hz in eight migraineurs) on 5 consecutive days can modify VEPs for longer periods. In all eight HV, the 1 Hz rTMS-induced dishabituation increased in duration over consecutive sessions and persisted between several hours (n = 4) and several weeks (n = 4) after the fifth session. In six out eight migraineurs, the normalization of VEP habituation by 10 Hz rTMS lasted longer after each daily stimulation but did not exceed several hours after the last session, except in two patients, where it persisted for 2 days and 1 week. Daily rTMS can thus induce long-lasting changes in cortical excitability and VEP habituation pattern. Whether this effect may be useful in preventative migraine therapy remains to be determined. [less ▲]

Long-term follow-up study of occipital nerve stimulation (ONS) for refractory chronic cluster headache: drastic change from short term outcome

Conference (2006)