Common data elements and data management: Remedy to cure underpowered preclinical studies.

Lack of translation of data obtained in preclinical trials to clinic has kindled researchers to develop new methodologies to increase the power and reproducibility of preclinical studies. One approach relates to harmonization of data collection and analysis, and has been used for a long time in clinical studies testing anti-seizure drugs. EPITARGET is a European Union FP7-funded research consortium composed of 18 partners from 9 countries.

KB-R7943, an inhibitor of the reverse Na(+)/Ca(2+) exchanger, does not modify secondary pathology in the thalamus following focal cerebral stroke in rats.

Remote areas connected to cortical infarcts, such as the thalamus, are affected by stroke due to delayed retrograde degeneration of afferent connections. This is temporally associated with the accumulation of β-amyloid (Aβ) and calcium. Here we tested a hypothesis that prevention of excessive Ca(2+) influx into the axoplasm via the reverse Na(+)/Ca(2+) exchanger (NCX) would provide axonal protection and eventually lessen the Aβ and calcium load in the thalamus.

Gender issues in antiepileptogenic treatments.

Disease modification of epilepsy refers to the alleviation of epileptogenesis or comorbidities after genetic or acquired epileptogenic brain insults. There are currently 30 proof-of-concept experimental pharmacologic studies that have demonstrated some beneficial disease-modifying effects. None of these studies, however, has yet passed from the laboratory to the clinic.

Lack of secondary pathology in the thalamus after focal cerebral ischemia in nonhuman primates.

Remote regions such as the thalamus undergo secondary degeneration after cerebral ischemia. In rodents, the pathology in the thalamus is characterized by a robust inflammatory reaction, β-amyloid (Aβ) accumulation and calcification. Here we studied whether nonhuman primates subjected to middle cerebral artery occlusion (MCAO) display a similar pathology.

Non-selective calcium channel blocker bepridil decreases secondary pathology in mice after photothrombotic cortical lesion.

Experimental studies have identified a complex link between neurodegeneration, β-amyloid (Aβ) and calcium homeostasis. Here we asked whether early phase β-amyloid pathology in transgenic hAPPSL mice exaggerates the ischemic lesion and remote secondary pathology in the thalamus, and whether a non-selective calcium channel blocker reduces these pathologies. Transgenic hAPPSL (n = 33) and non-transgenic (n = 30) male mice (4-5 months) were subjected to unilateral cortical photothrombosis and treated with the non-selective calcium channel blocker bepridil (50 mg/kg, p.

Bepridil decreases Aβ and calcium levels in the thalamus after middle cerebral artery occlusion in rats.

Alzheimer's disease (AD) and cerebral ischaemia share similar features in terms of altered amyloid precursor protein (APP) processing and β-amyloid (Aβ) accumulation. We have previously shown that Aβ and calcium deposition, and β-secretase activity, are robustly increased in the ipsilateral thalamus after transient middle cerebral artery occlusion (MCAO) in rats. Here, we investigated whether the non-selective calcium channel blocker bepridil, which also inhibits β-secretase cleavage of APP, affects thalamic accumulation of Aβ and calcium and in turn influences functional recovery in rats subjected to MCAO.

Experimental approaches to study functional recovery following cerebral ischemia.

Valid experimental models and behavioral tests are indispensable for the development of therapies for stroke. The translational failure with neuroprotective drugs has forced us to look for alternative approaches. Restorative therapies aiming to facilitate the recovery process by pharmacotherapy or cell-based therapy have emerged as promising options.

Chronic ibuprofen treatment does not affect the secondary pathology in the thalamus or improve behavioral outcome in middle cerebral artery occlusion rats.

Anti-inflammatory drug ibuprofen decreases the β-amyloid (Aβ) deposition and associated inflammation in transgenic Alzheimer disease mice. Based on this, we studied whether ibuprofen could modulate the secondary pathology described in the thalamus of middle cerebral artery occlusion (MCAO) rats. Our hypothesis was that ibuprofen could decrease inflammatory reaction and Aβ load in the thalamus of MCAO rats, which in turn is reflected in improved behavioral outcome.