Translational stroke research
-
Stroke, resulting from limited blood flow to the brain, is one of the most important causes of morbidity and mortality worldwide. Stroke is classified as ischemic, due to lack of blood flow, or hemorrhagic, due to bleeding. Because 87 % of strokes are classified as ischemic, this type will be the predominant focus of this review. ⋯ However, these approaches have not led to successful clinical outcomes. This review addresses the pathophysiology of stroke, neurogenesis after stroke, and how to stimulate these processes based on the current literature. Finally, ongoing clinical trials to improve neurological functions after stroke by enhancing neurogenesis are discussed in this review.
-
Oxidative stress plays an important role in cerebral ischemia-reperfusion injury. Dimethyl fumarate (DMF) and its primary metabolite monomethyl fumarate (MMF) are antioxidant agents that can activate the nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway and induce the expression of antioxidant proteins. Here, we evaluated the impact of DMF and MMF on ischemia-induced brain injury and whether the Nrf2 pathway mediates the effects provided by DMF and MMF in cerebral ischemia-reperfusion injury. ⋯ Further, DMF and MMF suppress glial activation following brain ischemia. Importantly, the protection of DMF and MMF was mostly evident during the subacute stage and was abolished in Nrf2-/- mice, indicating that the Nrf2 pathway is required for the beneficial effects of DMF and MMF. Together, our data indicate that DMF and MMF have therapeutic potential in cerebral ischemia-reperfusion injury and their protective role is likely mediated by the Nrf2 pathway.
-
Anesthetics have enabled major advances in development of experimental models of human stroke. Yet, their profound pharmacologic effects on neural function can confound the interpretation of experimental stroke research. Anesthetics have species-, drug-, and dose-specific effects on cerebral blood flow and metabolism, neurovascular coupling, autoregulation, ischemic depolarizations, excitotoxicity, inflammation, neural networks, and numerous molecular pathways relevant for stroke outcome. ⋯ Anesthetics also modulate systemic arterial blood pressure, lung ventilation, and thermoregulation, all of which may interact with the ischemic insult as well as the therapeutic interventions. These confounds present a dilemma. Here, we provide an overview of the anesthetic mechanisms of action and molecular and physiologic effects on factors relevant to stroke outcomes that can guide the choice and optimization of the anesthetic regimen in experimental stroke.
-
The present study investigates the association between hour-to-hour blood pressure (BP) variability and severe hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) during hyperacute stage. We analyzed hour-to-hour BP measurement within 24 h after IVT in patients with acute ischemic stroke. We calculated the maximum, minimum, and average (mean) of 24-h BP values, and BP variability profiles including standard deviation (SD), average squared difference between successive measurements (SV), average squared difference between rise and drop successive measurements (SV rise and SV drop), and maximum of SV rise and SV drop (SVrisemax and SVdropmax) after quartering 0-to-24 h BP course. ⋯ Binary logistic regression indicated that SBPSD and SBPSV within the first 24 h were associated with sICH (OR, 4.538; 95 % CI, 1.834-11.230; p = 0.001 and OR, 6.117; 95 % CI, 2.000-18.711; p = 0.002) and PH (OR, 2.146; 95 % CI, 1.106-4.165; p = 0.024 and OR, 2.202; 95 % CI, 1.046-4.633; p = 0.038). For the SBP SV parameters among four periods of the initial 24 h, only SV, SVrise, and SVrisemax during the first 6 h were significantly associated with sICH (OR, 2.785; 95 % CI, 1.294-5.994; p = 0.009; OR, 1.825; 95 % CI, 1.110-3.002; p = 0.018 and OR, 1.495; 95 % CI, 1.039-2.149; p = 0.030) and PH (OR, 2.088; 95 % CI, 1.287-3.387; p = 0.003; OR, 1.501; 95 % CI, 1.044-2.156; p = 0.028 and OR, 1.334; 95 % CI, 1.023-1.739; p = 0.033). High systolic BP variability during the first 6 h after IVT was related with severe HTs, which highlights the potential predictability to severe HTs.
-
Observational Study
Co-ultramicronized Palmitoylethanolamide/Luteolin in the Treatment of Cerebral Ischemia: from Rodent to Man.
Acute ischemic stroke, the most frequent cause of permanent disability in adults worldwide, results from transient or permanent reduction in regional cerebral blood flow and involves oxidative stress and inflammation. Despite the success of experimental animal models of stroke in identifying anti-inflammatory/neuroprotective compounds, translation of these putative neuroprotectants to human clinical trials has failed to produce a positive outcome. Tissue injury and stress activate endogenous mechanisms which function to restore homeostatic balance and prevent further damage by upregulating the synthesis of lipid signaling molecules, including N-palmitoylethanolamine (PEA or palmitoylethanolamide). ⋯ All indices showed statistically significant gains at study end. Despite its observational nature, this represents the first description of co-ultraPEALut administration to human stroke patients and clinical improvement not otherwise expected from spontaneous recovery. Further, controlled trials are warranted to confirm the utility of co-ultraPEALut to improve clinical outcome in human stroke.