Conditioned Medium from Bone marrow-derived Mesenchymal Stem Cells improves recovery after Spinal Cord Injury in rats: an original strategy to avoid cell transplantation.
CANTINIEAUX, Dorothée ; ; BLACHER, Silvia et al
in PLoS ONE (2013), 8(8), 69515
Spinal cord injury triggers irreversible loss of motor and sensory functions. Numerous strategies aiming at repairing the injured spinal cord have been studied. Among them, the use of bone marrow-derived ... [more ▼]
Spinal cord injury triggers irreversible loss of motor and sensory functions. Numerous strategies aiming at repairing the injured spinal cord have been studied. Among them, the use of bone marrow-derived mesenchymal stem cells (BMSCs) is promising. Indeed, these cells possess interesting properties to modulate CNS environment and allow axon regeneration and functional recovery. Unfortunately, BMSC survival and differentiation within the host spinal cord remain poor, and these cells have been found to have various adverse effects when grafted in other pathological contexts. Moreover, paracrine-mediated actions have been proposed to explain the beneficial effects of BMSC transplantation after spinal cord injury. We thus decided to deliver BMSC-released factors to spinal cord injured rats and to study, in parallel, their properties in vitro. We show that, in vitro, BMSC-conditioned medium (BMSC-CM) protects neurons from apoptosis, activates macrophages and is pro-angiogenic. In vivo, BMSC-CM administered after spinal cord contusion improves motor recovery. Histological analysis confirms the pro-angiogenic action of BMSC-CM, as well as a tissue protection effect. Finally, the characterization of BMSC-CM by cytokine array and ELISA identified trophic factors as well as cytokines likely involved in the beneficial observed effects. In conclusion, our results support the paracrine-mediated mode of action of BMSCs and raise the possibility to develop a cell-free therapeutic approach. [less ▲]Detailed reference viewed: 67 (12 ULg)
Stimulation of the sphenopalatine ganglion (SPG) for cluster headache treatment. Pathway CH-1: A randomized, sham-controlled study.
Schoenen, Jean ; ; et al
in Cephalalgia : An International Journal of Headache (2013)
BackgroundThe pain and autonomic symptoms of cluster headache (CH) result from activation of the trigeminal parasympathetic reflex, mediated through the sphenopalatine ganglion (SPG). We investigated the ... [more ▼]
BackgroundThe pain and autonomic symptoms of cluster headache (CH) result from activation of the trigeminal parasympathetic reflex, mediated through the sphenopalatine ganglion (SPG). We investigated the safety and efficacy of on-demand SPG stimulation for chronic CH (CCH).MethodsA multicenter, multiple CH attack study of an implantable on-demand SPG neurostimulator was conducted in patients suffering from refractory CCH. Each CH attack was randomly treated with full, sub-perception, or sham stimulation. Pain relief at 15 minutes following SPG stimulation and device- or procedure-related serious adverse events (SAEs) were evaluated.FindingsThirty-two patients were enrolled and 28 completed the randomized experimental period. Pain relief was achieved in 67.1% of full stimulation-treated attacks compared to 7.4% of sham-treated and 7.3% of sub-perception-treated attacks (p < 0.0001). Nineteen of 28 (68%) patients experienced a clinically significant improvement: seven (25%) achieved pain relief in >/=50% of treated attacks, 10 (36%), a >/=50% reduction in attack frequency, and two (7%), both. Five SAEs occurred and most patients (81%) experienced transient, mild/moderate loss of sensation within distinct maxillary nerve regions; 65% of events resolved within three months.InterpretationOn-demand SPG stimulation using the ATI Neurostimulation System is an effective novel therapy for CCH sufferers, with dual beneficial effects, acute pain relief and observed attack prevention, and has an acceptable safety profile compared to similar surgical procedures. [less ▲]Detailed reference viewed: 34 (2 ULg)
Behavior in the open field predicts the number of KCl-induced cortical spreading depressions in rats.
; ; Koulchitsky, Stanislav et al
in Behavioural Brain Research (2013), 236(1), 90-3
Anxiety disorders are known to be comorbid with migraine, and cortical spreading depression (CSD) is the most likely cause of the migraine aura. To search for possible correlations between susceptibility ... [more ▼]
Anxiety disorders are known to be comorbid with migraine, and cortical spreading depression (CSD) is the most likely cause of the migraine aura. To search for possible correlations between susceptibility to CSD and anxiety we used the open field test in male Sprague-Dawley rats chronically treated with the preventive anti-migraine drugs valproate or riboflavin. Animals avoiding the central area of the open field chamber and those with less exploratory activity (i.e. rearing) were considered more anxious. After 4 weeks of treatment CSDs were elicited by application of 1M KCl over the occipital cortex and the number of CSDs occurring over a 2h period was compared to the previously assessed open field behavior. Higher anxiety-like behavior was significantly correlated with a higher frequency of KCl-induced CSDs. In saline-treated animals, fewer rearings were found in animals with more frequent CSDs (R=-1.00). The duration of ambulatory episodes in the open field center correlated negatively with number of CSDs in the valproate group (R=-0.83; p<0.005) and in riboflavin treated group (R=-0.69; p<0.05) as well as total time spent in the open field center in both groups (R=-0.75; p<0.05 and R=-0.58; p<0.1 respectively). These results suggest that anxiety symptoms are associated with susceptibility to CSD and might explain why it can be an aggravating factor in migraine with aura. [less ▲]Detailed reference viewed: 35 (14 ULg)
Ovarian hormones modulate occurrence of cortical spreading depression and its suppression by L-kynurenine in rat
Chauvel, Virginie ; Multon, Sylvie ; Schoenen, Jean
Poster (2012, October 27)Detailed reference viewed: 16 (4 ULg)
Cluster headache Award 2012: Central modulation in cluster headache patients treated with occipital nerve stimulation
MAGIS, Delphine ; Bruno, Marie-Aurélie ; FUMAL, Arnaud et al
in Journal of Headache & Pain (2012, September 16)Detailed reference viewed: 32 (6 ULg)
High frequency headache prevalence and management in primary care. A survey among general practitioners of the Liege area, Belgium
MAGIS, Delphine ; Schoenen, Jean
in Frontiers in Human Neuroscience (2012, September 12)Detailed reference viewed: 23 (1 ULg)
Influence of ovarian hormones on suppressive effect of kynurenine administration upon cortical spreading depression
Chauvel, Virginie ; Multon, Sylvie ; Schoenen, Jean
Poster (2012, September)Detailed reference viewed: 16 (4 ULg)
Anodal transcranial direct current stimulation over the visual cortex as a preventive treatment of migraine: a proof-of-concept study.
; ; SAVA, Simona Liliana et al
in Frontiers in Human Neuroscience (2012, September)Detailed reference viewed: 44 (2 ULg)
Theta burst and quadripulse repetitive Transcranial Magnetic Stimulation (rTMS) may have therapeutic potentials in migraine prevention: a proof-of-concept study in healthy volunteers and a pilot-trial in migraine patients.
; ; SAVA, Simona Liliana et al
in Frontiers in Human Neuroscience (2012, September)Detailed reference viewed: 57 (2 ULg)
A novel CACNA1A mutation results in episodic ataxia with migrainous features without headache
MAGIS, Delphine ; ; et al
in Cephalalgia : An International Journal of Headache (2012)Detailed reference viewed: 19 (1 ULg)
Advances and challenges in neurostimulation for headaches
MAGIS, Delphine ; Schoenen, Jean
in Lancet Neurology (2012), 11(8), 708-719Detailed reference viewed: 42 (1 ULg)
Neurostimulation therapies for primary headache disorders: present and future
MAGIS, Delphine ; ; Schoenen, Jean
in Current Opinion in Neurology (2012), 25(3), 269-276
Purpose of review Most pharmacological treatments of primary headache disorders are partially effective and have cumbersome side effects. Therapies with better efficacy and tolerance are needed ... [more ▼]
Purpose of review Most pharmacological treatments of primary headache disorders are partially effective and have cumbersome side effects. Therapies with better efficacy and tolerance are needed. Neurostimulation techniques may have this potential. This is an attempt to summarize the latest clinical trial results published in the field. Recent findings Hypothalamic deep brain stimulation is effective in drug-resistant chronic cluster headache (drCCH) but not riskless. Recent anatomical MRI studies indicate that the effective stimulation sites are rather widespread. Occipital nerve stimulation (ONS) seems to be effective in up to 76% of drCCH patients and its benefit long-lasting. A minority of patients are able to abandon preventive drugs. Its mechanism of action appears nonspecific. In chronic migraine, randomized controlled trials of ONS showed recently encouraging results, but long-term studies are missing. An ongoing sham-controlled trial suggests sphenopalatine ganglion neurostimulation (SPGS) efficacy in drCCH acute treatment, but possibly also in preventive therapy. Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) modulate cortical excitability and connectivity. TMS could prevent headache when applied over the occipital cortex during the migraine aura. Repetitive TMS and tDCS have provided mixed results in a few small studies and warrant further trials. Summary Neurostimulation therapies inaugurate a new era in headache management and offer a promising alternative to medications. Future studies are necessary to provide evidence-based efficacy data, knowledge on their mode of action and information about their pharmaco-economic advantages. [less ▲]Detailed reference viewed: 66 (0 ULg)
Genome-wide association analysis identifies susceptibility loci for migraine without aura.
; ; et al
in Nature Genetics (2012), 44(7), 777-82
Migraine without aura is the most common form of migraine, characterized by recurrent disabling headache and associated autonomic symptoms. To identify common genetic variants associated with this ... [more ▼]
Migraine without aura is the most common form of migraine, characterized by recurrent disabling headache and associated autonomic symptoms. To identify common genetic variants associated with this migraine type, we analyzed genome-wide association data of 2,326 clinic-based German and Dutch individuals with migraine without aura and 4,580 population-matched controls. We selected SNPs from 12 loci with 2 or more SNPs associated with P values of <1 x 10(-5) for replication testing in 2,508 individuals with migraine without aura and 2,652 controls. SNPs at two of these loci showed convincing replication: at 1q22 (in MEF2D; replication P = 4.9 x 10(-4); combined P = 7.06 x 10(-11)) and at 3p24 (near TGFBR2; replication P = 1.0 x 10(-4); combined P = 1.17 x 10(-9)). In addition, SNPs at the PHACTR1 and ASTN2 loci showed suggestive evidence of replication (P = 0.01; combined P = 3.20 x 10(-8) and P = 0.02; combined P = 3.86 x 10(-8), respectively). We also replicated associations at two previously reported migraine loci in or near TRPM8 and LRP1. This study identifies the first susceptibility loci for migraine without aura, thereby expanding our knowledge of this debilitating neurological disorder. [less ▲]Detailed reference viewed: 34 (6 ULg)
Multidsiciplinary Management of Migraine: Pharmacological, Manual And Other Therapies.
; ; Schoenen, Jean
Book published by Jones & Bartlett Learning (2012)Detailed reference viewed: 134 (2 ULg)
A comprehensive view of migraine pathophysiology
; ; et al
in Fernandez-de-las-Penas, C; Chaitow, L; Schoenen, Jean (Eds.) Multidisciplinary Management of Migraine (2012)Detailed reference viewed: 33 (3 ULg)
Effects of repetitive transcranial magnetic stimulation on somatosensory evoked potentials and high frequency oscillations in migraine.
; ; et al
in Cephalalgia : An International Journal of Headache (2012), 32(9), 700-9
Background: In previous studies we found that high-frequency somatosensory oscillations (HFOs) reflecting thalamo-cortical activation were decreased in migraineurs between attacks and that high-frequency ... [more ▼]
Background: In previous studies we found that high-frequency somatosensory oscillations (HFOs) reflecting thalamo-cortical activation were decreased in migraineurs between attacks and that high-frequency repetitive transcranial magnetic stimulation (rTMS) was able to normalize the habituation deficit of visual evoked potentials (VEPs). Here we study the effects of activating (10 Hz) or inhibiting (1 Hz) rTMS on conventional low-frequency (LF) and high-frequency somatosensory evoked potentials (SSEPs). Subjects and methods: rTMS was applied on the motor cortex of 13 healthy volunteers (HVs) and 13 migraine without aura (MO) patients. We measured N20-P25 LF-SSEP amplitude and habituation, and maximal peak-to-peak amplitude of early and late HFOs before and after rTMS. Results: In HVs, 1 Hz rTMS significantly reduced the amplitude of the first LF-SSEP block and its habituation. In MO patients, 10 Hz rTMS increased the amplitude of the first block and induced habituation. Ten Hz rTMS produced an increase of late HFO in both groups, but more interestingly, in MO patients also significantly increased the early HFOs, which are reduced at baseline compared to those of HVs. Conclusions: These data confirm for SSEP that excitatory rTMS can normalize habituation in migraine patients and show that this is accompanied by early an HFO increase, which is thought to reflect thalamo-cortical activity. Taken together with similar effects we observed for VEPs, this finding supports the hypothesis that dysfunctioning thalamo-cortical loops may be responsible for the interictal habituation deficit in migraine. [less ▲]Detailed reference viewed: 11 (0 ULg)
Efficacy and tolerability of lasmiditan, an oral 5-HT(1F) receptor agonist, for the acute treatment of migraine: a phase 2 randomised, placebo-controlled, parallel-group, dose-ranging study.
; ; et al
in Lancet Neurology (2012), 11(5), 405-13
BACKGROUND: Lasmiditan (COL-144) is a novel, centrally acting, highly selective 5-HT(1F) receptor agonist without vasoconstrictor activity that seemed effective when given as an intravenous infusion in a ... [more ▼]
BACKGROUND: Lasmiditan (COL-144) is a novel, centrally acting, highly selective 5-HT(1F) receptor agonist without vasoconstrictor activity that seemed effective when given as an intravenous infusion in a proof-of-concept migraine study. We aimed to assess the efficacy and safety of oral lasmiditan for the acute treatment of migraine. METHODS: In this multicentre, double-blind, parallel-group, dose-ranging study in 43 headache centres in five European countries, patients with migraine with and without aura and who were not using prophylaxis were randomly assigned (1:1:1:1:1) to treat one moderate or severe attack at home with 50 mg, 100 mg, 200 mg, or 400 mg lasmiditan, or placebo. Study drug and placebo were supplied in identical numbered tablet packs. The randomisation code was generated by an independent statistician. Patients and investigators were masked to treatment allocation. The primary endpoint was dose response for headache relief (moderate or severe becoming mild or none) at 2 h. The primary analysis was done in the modified intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00883051. FINDINGS: Between July 8 2009, and Feb 18, 2010, 512 patients were randomly assigned to treatment, 391 of whom received treatment. 86 patients received placebo (81 included in primary analysis) and 305 received lasmiditan (50 mg n=79, 100 mg n=81, 200 mg n=69, and 400 mg n=68 included in primary analysis). There was a linear association between headache response rate at 2 h and lasmiditan dose (Cochran-Armitage test p<0.0001). Every lasmiditan treatment dose significantly improved headache response at 2 h compared with placebo (lasmiditan 50 mg: difference 17.9%, 95% CI 3.9-32.1, p=0.022; 100 mg: 38.2%, 24.1-52.4, p<0.0001; 200 mg: 28.8%, 9.6-39.9, p=0.0018; 400 mg: 38.7%, 23.9-53.6, p<0.0001). The proportion of patients with treatment-emergent adverse events increased with increasing doses (53/82 [65%], 59/82 [72%], 61/71 [86%], and 59/70 [84%] for lasmiditan 50, 100, 200, and 400 mg, respectively vs 19/86 [22%] for placebo). Most adverse events were mild or moderate in intensity, with 16 of 82 (20%), 23 of 82 (28%), 28 of 71 (39%), and 31 of 70 (44%) of patients on lasmiditan 50, 100, 200, and 400 mg, respectively reporting a severe adverse event compared with five of 86 (6%) on placebo. The most common adverse events were CNS related and included dizziness, fatigue, vertigo, paraesthesia, and somnolence. INTERPRETATION: Oral lasmiditan seems to be safe and effective in the acute treatment of migraine. Further assessment in larger placebo-controlled and triptan-controlled trials are needed to assess the potential role of lasmiditan in acute migraine therapy. FUNDING: CoLucid Pharmaceuticals. [less ▲]Detailed reference viewed: 180 (0 ULg)