Neuroprotective strategies and the underlying molecular basis of cerebrovascular stroke

Abstract

<jats:p>Stroke is a leading cause of disability in the US. Although there has been significant progress in the area of medical and surgical thrombolytic technologies, neuroprotective agents to prevent secondary cerebral injury and to minimize disability remain limited. Only limited success has been reported in preclinical and clinical trials evaluating a variety of compounds. In this review, the authors discuss the most up-to-date information regarding the underlying molecular biology of stroke as well as strategies that aim to mitigate this complex signaling cascade. Results of historical research trials involving <jats:italic>N</jats:italic>-methyl-<jats:sc>d</jats:sc>-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor antagonists, clomethiazole, antioxidants, citicoline, nitric oxide, and immune regulators have laid the groundwork for current progress. In addition, more recent studies involving therapeutic hypothermia, magnesium, albumin, glyburide, uric acid, and a variety of other treatments have provided more options. The use of neuroprotective agents in combination or with existing thrombolytic treatments may be one of many exciting areas of further development. Although past trials of neuroprotective agents in ischemic stroke have been limited, significant insights into mechanisms of stroke, animal models, and trial design have incrementally improved approaches for future therapies.</jats:p>

In Vivo Imaging of Microglial Calcium Signaling in Brain Inflammation and Injury

“…Evidently, the effects of inflammatory cytokines in stroke progression are significant and complex, and uncovering the patterns and potential blockers of Ca 2+ activity in microglia may instruct new ways to control cytokine release. Currently, anti-inflammatory mechanisms are being evaluated in a clinical phase II trial of ischemic stroke which targets the interleukin-1 signaling pathway via recombinant antagonist IL-1Ra/anakinra [ 127 ]. It is plausible to suggest that better understanding microglial Ca 2+ dynamics in the course of ischemic injury and spreading depolarizations will identify new targets for therapeutic intervention.…”

The neuroprotective action of 3,3′-diindolylmethane against ischemia involves an inhibition of apoptosis and autophagy that depends on HDAC and AhR/CYP1A1 but not ERα/CYP19A1 signaling

“…Unfortunately, both rt-PA and hypothermia have narrow therapeutic window, low levels of specificity and efficacy, and long list of contraindications. Moreover, many neuroprotective agents that showed positive results in experimental models of stroke failed in clinical trials [ 4 , 5 ]. For that reason, there is a strong need to find a novel effective compound that may protect the brain undergoing ischemia at different stages of development.…”

The efficacy of recognan in the early stage of ischemic stroke

“…Все клинические и фармакологические эффекты цитиколина обусловлены восстановлением поврежденных мембран клеток [12]. Препарат ингибирует действие фосфолипаз, препятствуя избыточному образованию свободных радикалов, а также предотвращает гибель клеток, воздействуя на механизмы апоптоза [13].…”