Aquaporins in neurological disorders

Aquaporins (AQPs) are water channel molecules that allow the passage of water through the lipid bilayers of cell membranes. AQP1, AQP4 and AQP9 are expressed in the central nervous system and AQP4 is well known as the target of auto-antibodies in Devic’s neuromyelitis optica. The role of AQPs in facilitating water movements suggests a link with oedema formation and resolution in the brain. Furthermore, AQPs are also involved in process formation in glial cells with a close link to neuroinflammation. This mini-review gives an overview of what is currently known about the role of AQPs in different neurological disorders

Extended preclinical investigation of lactate for neuroprotection after ischemic stroke

Lactate has been shown to have beneficial effect both in experimental ischemia–reperfusion models and in human acute brain injury patients. To further investigate lactate’s neuroprotective action in experimental in vivo ischemic stroke models prior to its use in clinics, we tested (1) the outcome of lactate administration on permanent ischemia and (2) its compatibility with the only currently approved drug for the treatment of acute ischemic stroke, recombinant tissue plasminogen activator (rtPA), after ischemia–reperfusion. We intravenously injected mice with 1 µmol/g sodium l -lactate 1 h or 3 h after permanent middle cerebral artery occlusion (MCAO) and looked at its effect 24 h later. We show a beneficial effect of lactate when administered 1 h after ischemia onset, reducing the lesion size and improving neurological outcome. The weaker effect observed at 3 h could be due to differences in the metabolic profiles related to damage progression. Next, we administered 0.9 mg/kg of intravenous (iv) rtPA, followed by intracerebroventricular injection of 2 µL of 100 mmol/L sodium l -lactate to treat mice subjected to 35-min transient MCAO and compared the outcome (lesion size and behavior) of the combined treatment with that of single treatments. The administration of lactate after rtPA has positive influence on the functional outcome and attenuates the deleterious effects of rtPA, although not as strongly as lactate administered alone. The present work gives a lead for patient selection in future clinical studies of treatment with inexpensive and commonly available lactate in acute ischemic stroke, namely patients not treated with rtPA but mechanical thrombectomy alone or patients without recanalization therapy

The effect of continuous positive airway pressure on total cerebral blood flow in healthy awake volunteers

Purpose: Continuous positive airway pressure (CPAP) is the gold standard treatment for obstructive sleep apnea. However, the physiologic impact of CPAP on cerebral blood flow (CBF) is not well established. Ultrasound can be used to estimate CBF, but there is no widespread accepted protocol. We studied the physiologic influence of CPAP on CBF using a method integrating arterial diameter and flow velocity (FV) measurements obtained for each vessel supplying blood to the brain. Methods: FV and lumen diameter of the left and right internal carotid, vertebral, and middle cerebral arteries were measured using duplex Doppler ultrasound with and without CPAP at 15cmH2O, applied in a random order. Transcutaneous carbon dioxide (PtcCO2), heart rate (HR), blood pressure (BP), and oxygen saturation were monitored. Results were compared with a theoretical prediction of CBF change based on the effect of partial pressure of carbon dioxide on CBF. Results: Data were obtained from 23 healthy volunteers (mean ± SD; 12 male, age 25.1 ± 2.6years, body mass index 21.8 ± 2.0kg/m2). The mean experimental and theoretical CBF decrease under CPAP was 12.5% (p < 0.001) and 11.9% (p < 0.001), respectively. The difference between experimental and theoretical CBF reduction was not statistically significant (3.84 ± 79ml/min, p = 0.40). There was a significant reduction in PtcCO2 with CPAP (p = <0.001) and a significant increase in mean BP (p = 0.0017). No significant change was observed in SaO2 (p = 0.21) and HR (p = 0.62). Conclusion: Duplex Doppler ultrasound measurements of arterial diameter and FV allow for a noninvasive bedside estimation of CBF. CPAP at 15cmH2O significantly decreased CBF in healthy awake volunteers. This effect appeared to be mediated predominately through the hypocapnic vasoconstriction coinciding with PCO2 level reduction. The results suggest that CPAP should be used cautiously in patients with unstable cerebral hemodynamic

Carotid plaque surface echogenicity predicts cerebrovascular events: An Echographic Multicentric Swiss Study.

BACKGROUND AND PURPOSE To determine the prognostic value for ischemic stroke or transitory ischemic attack (TIA) of plaque surface echogenicity alone or combined to degree of stenosis in a Swiss multicenter cohort METHODS: Patients with ≥60% asymptomatic or ≥50% symptomatic carotid stenosis were included. Grey-scale based colour mapping was obtained of the whole plaque and of its surface defined as the regions between the lumen and respectively 0-0.5, 0-1, 0-1.5, and 0-2 mm of the outer border of the plaque. Red, yellow and green colour represented low, intermediate or high echogenicity. Proportion of red color on surface (PRCS) reflecting low echogenictiy was considered alone or combined to degree of stenosis (Risk index, RI). RESULTS We included 205 asymptomatic and 54 symptomatic patients. During follow-up (median/mean 24/27.7 months) 27 patients experienced stroke or TIA. In the asymptomatic group, RI ≥0.25 and PRCS ≥79% predicted stroke or TIA with a hazard ratio (HR) of respectively 8.7 p = 0.0001 and 10.2 p < 0.0001. In the symptomatic group RI ≥0.25 and PRCS ≥81% predicted stroke or TIA occurrence with a HR of respectively 6.1 p = 0.006 and 8.9 p = 0.001. The best surface parameter was located at 0-0.5mm. Among variables including age, sex, degree of stenosis, stenosis progression, RI, PRCS, grey median scale values and clinical baseline status, only PRCS independently prognosticated stroke (p = 0.005). CONCLUSION In this pilot study including patients with at least moderate degree of carotid stenosis, PRCS (0-0.5mm) alone or combined to degree of stenosis strongly predicted occurrence of subsequent cerebrovascular events

Antiagrégation plaquettaire en prévention secondaire de l’AVC ischémique

De nouvelles études permettent de mieux définir le rôle des différents traitements antiagrégants en prévention secondaire des accidents vasculaires cérébraux (AVC) non cardioemboliques. Le traitement de base de l’antiagrégation est l’aspirine. Le clopidogrel et la combinaison aspirine plus dipyridamole sont des alternatives crédibles avec une protection légèrement supérieure. Le ticagrélor, inhibiteur réversible du récepteur P2Y12 utilisé en cardiologie, n’a pas démontré de supériorité par rapport à l’aspirine. En phase précoce, une double antiagrégation par aspirine et clopidogrel peut être utilisée, diminuant le risque de récidive. Ce bénéfice est le plus important lorsque la cause est artério-embolique. La durée de la double antiagrégation ne doit pas dépasser trois mois au vu du risque hémorragique important à long terme