Age and diet modify acute microhemorrhage outcome in the mouse brain.

Cerebral microhemorrhages (CMHs) are considered as asymptomatic lesions, but might impair cognition in non-demented elderly individuals. The aging process includes poor vascular health, enhanced at midlife by metabolic disturbances upon high-fat diet (HFD). The onset of CMHs could thus have more serious consequences in midlife subjects with metabolic disturbances.

Visceral adiposity links cerebrovascular dysfunction to cognitive impairment in middle-aged mice.

Midlife cognitive decline is now recognized as a factor of poor prognosis for late-life dementia. Although an epidemiological link has been suggested with high fat diet (HFD)-induced metabolic disorders, the effect of a long period of HFD on midlife cerebrovascular and cognitive functions remains unproven. A cohort of 216 young mice was fed with HFD up to middle age (12 months), and kinetically characterized for metabolic status, including weight, blood lipid profile, hepatic fat accumulation, glucose intolerance, and visceral adiposity.

Safety of oral anticoagulants on experimental brain microbleeding and cognition.

This study aims at determining the ability of clinical-based doses of four oral anticoagulants to transform the onset of a cerebral microhemorrhages (CMH) burden into a symptomatic intracerebral hemorrhage (ICH) in the healthy brain, and precipitate cognitive impairment. Wild-type mice were anticoagulated for 10 days using apixaban, rivaroxaban or dabigatran as direct oral anticoagulants (DOACs), or warfarin as vitamin K-antagonist. Meanwhile, a burden of ∼20 CMHs was induced in the Sylvian territory by intra-carotid injection of cyclodextrin nanoparticles.

Neither nefopam nor acetaminophen can be used as postoperative analgesics in a rat model of ischemic stroke.

Unlabelled: Analgesics such as opioid agonists are usually not given during the postoperative phase of experimental stroke because they are susceptible to interfere with the evaluation of neuroprotective therapies. Here, we investigate the potential of acetaminophen and nefopam, two nonopioid analgesic drugs, to exert an analgesic effect without inducing neuroprotection in a murine model of ischemic stroke. We demonstrate that acetaminophen (200 mg/kg, PO) induces a significant decrease in the infarct volume, particularly in the cortex (VEHICLE: 200.

Ferroptosis, a newly characterized form of cell death in Parkinson's disease that is regulated by PKC.

Parkinson's disease (PD) is a complex illness characterized by progressive dopaminergic neuronal loss. Several mechanisms associated with the iron-induced death of dopaminergic cells have been described. Ferroptosis is an iron-dependent, regulated cell death process that was recently described in cancer.

Evidence for the use of isoflurane as a replacement for chloral hydrate anesthesia in experimental stroke: an ethical issue.

Since an ethical issue has been raised regarding the use of the well-known anesthetic agent chloral hydrate, owing to its mutagenic and carcinogenic effects in animals, attention of neuroscientists has turned to finding out an alternative agent able to meet not only potency, safety, and analgesic efficacy, but also reduced neuroprotective effect for stroke research. The aim of this study was to compare the potential of chloral hydrate and isoflurane for both modulating the action of the experimental neuroprotectant MK801 and exerting analgesia. After middle cerebral artery occlusion in rats, no difference was observed in 24 h survival rate, success of ischemia, or infarct volume reduction between both anesthetics.

Effects of the PPAR-α agonist fenofibrate on acute and short-term consequences of brain ischemia.

In stroke, there is an imperative need to develop disease-modifying drugs able to (1) induce neuroprotection and vasculoprotection, (2) modulate recovery and brain plasticity, and (3) limit the short-term motor and cognitive consequences. We hypothesized that fenofibrate, a peroxisome proliferator-activated receptor-α (PPAR-α) agonist, could exert a beneficial effect on immediate and short-term poststroke consequences related to its pleiotropic mechanisms. Rats or mice were subjected to focal ischemia to determine the effects of acute treatment by fenofibrate on (i) motor and memory impairment, (2) both cerebral and vascular compartments, (3) inflammation, (4) neurogenesis, and (5) amyloid cascade.

Time-induced progressive alteration of kir current in cerebral smooth muscle cells of stroke-prone spontaneously hypertensive rats.

We investigated the involvement of potassium inward rectifier current (Kir) impairment in smooth muscle cells of cerebral arteries under the condition of increased susceptibility of stroke, in spontaneously hypertensive stroke-prone (SHRsp) rats compared to spontaneously hypertensive (SHR) ones as well as to controls (WKY). Kir current was studied with whole-cell patch-clamp techniques on freshly isolated single smooth muscle cells (SMC) of middle cerebral artery (MCA) from SHRsp, SHR, and WKY male rats (are range 12-32 weeks). A significant and progressive Kir current density reduction was observed on SMC of SHRsp rats from the 22nd week of age on, as opposed to the Kir current density stability observed over the same time in the SMC of WKY and SHR rats.

PPARs: a potential target for a disease-modifying strategy in stroke.

Stroke is one of the major causes of mortality and disability in adults in industrialized countries. Despite numerous preclinical studies and clinical trials in the field of cerebral ischemia, no pharmacological agent has been validated in the treatment of acute ischemic, except thrombolysis. Cerebral ischemia is not only a neuronal disease but it affects the entire neurovascular unit.

Withdrawal of fenofibrate treatment partially abrogates preventive neuroprotection in stroke via loss of vascular protection.

To explore the mechanisms of action of preventive neuroprotection induced by PPAR-alpha activation, we have evaluated the neuronal, vascular effects of preventive treatment with fenofibrate up until the induction of experimental brain ischaemia and fenofibrate treatment withdrawn 3days before ischaemia induction. Fenofibrate (200mg/kg/day) was administered in rats for 14days or withdrawn 3days before induction of cerebral ischaemia. Animals underwent a 1-hour middle cerebral artery occlusion (MCAo), followed by reperfusion for 24h.

Pharmacological neutropenia prevents endothelial dysfunction but not smooth muscle functions impairment induced by middle cerebral artery occlusion.

1. The polymorphonuclear neutrophils (PMN) activation and mobilization observed in acute cerebral infarction contribute to the brain tissue damage, but PMN could also be involved in postischemic functional injury of ischemied blood vessel. 2.

The neuroprotective effect of the antioxidant flavonoid derivate di-tert-butylhydroxyphenyl is parallel to the preventive effect on post-ischemic Kir2.x impairment but not to post-ischemic endothelial dysfunction.

In the rat model of transient cerebral ischemia induced by intraluminal occlusion of the middle cerebral artery, we investigated the respective roles of ischemia and reperfusion in endothelium-dependent relaxation and smooth muscle relaxation related to the inward rectifier potassium current (Kir2.x), using the Halpern arteriography technique and/or patch-clamp technique. We first demonstrated that reperfusion is necessary to induce a significant impairment of smooth muscle Kir2.

Risperidone reduces K+ currents in human atrial myocytes and prolongs repolarization in human myocardium.

The antipsychotic agent risperidone has been shown to cause QT prolongation. In rabbit heart preparations, we have demonstrated that risperidone markedly lengthened action potential duration and blocked the delayed rectifier current, I(Kr.) The current study was designed to investigate the risperidone effects: (i) on the main K(+) repolarizing currents on human atrial myocytes, using whole-cell patch clamp recordings; (ii) on action potentials recorded from human atrial and ventricular myocardium using conventional microelectrodes.

Clarithromycin reduces Isus and Ito currents in human atrial myocytes with minor repercussions on action potential duration.

The macrolide antibacterial agent clarithromycin has been shown to cause QT interval prolongation on the electrocardiogram. In rabbit heart preparations clarithromycin (concentration dependently) lengthened the action potential duration and blocked the delayed rectifier current. The aim of the present study was to investigate the clarithromycin effects: (i) on the Ca2+ L-type and the main K+ repolarizing currents on human atrial myocytes, using whole-cell patch clamp recordings and (ii) on action potentials recorded from human atrial and ventricular myocardium using conventional microelectrodes.

Delayed cerebrovascular protective effect of lipopolysaccharide in parallel to brain ischemic tolerance.

Cerebrovascular abnormalities, in endothelium and smooth muscle compartments, occur in the course of cerebral ischemia-reperfusion as evidenced by the impairment of endothelium-dependent relaxation and decrease in potassium inward rectifier density in occluded middle cerebral arteries (MCAs). The authors investigated whether a delayed vascular protection occurred in a model of brain ischemic tolerance. A low dose of lipopolysaccharide (0.

Risperidone prolongs cardiac action potential through reduction of K+ currents in rabbit myocytes.

Prolongation of QT interval by antipsychotic drugs is an unwanted side effect that may lead to ventricular arrhythmias. The antipsychotic agent risperidone has been shown to cause QT prolongation, especially in case of overdosage. We investigated risperidone effects on action potentials recorded from rabbit Purkinje fibers and ventricular myocardium and on potassium currents recorded from atrial and ventricular rabbit isolated myocytes.

Repolarization abnormalities and their arrhythmogenic consequences in porcine tachycardia-induced cardiomyopathy.

Objectives: Action potential prolongation related to the alteration of several membrane currents is constantly reported in heart failure (HF) but reports about its role in arrhythmogenesis are sparse. Our aim was to determine, by analogy with long QT syndromes, whether prolonged repolarization is associated with increased dispersion or linked to bradycardia-dependent ventricular arrhythmias in pacing-induced cardiomyopathy.

Methods: QT intervals, action potentials and transmural activation-to-recovery intervals (ARIs) along with whole-cell delayed rectifier (I(K)) and transient outward (I(to1)) K+ currents were recorded in left ventricle from pigs with HF and controls.