There is a strong link between hypoperfusion and white matter (WM) damage in patients with leukoaraiosis and vascular cognitive impairment (VCI). Other than management of vascular risk factors, there is no treatment for WM damage and VCI that delays progression of the disease process to dementia. Observational studies suggest that exercise may prevent or slow down the progression of Alzheimer's disease (AD) and VCI. However, getting patients to exercise is challenging, especially with advancing age and disability. Remote ischemic conditioning, an "exercise equivalent," allows exercise to be given with a "device" at home for long periods of time. Since remote ischemic conditioning (RIC) increases cerebral blood flow (CBF) in preclinical studies and in humans, RIC may be an ideal therapy to treat VCI and WM disease and perhaps even sporadic AD. By using magnetic resonance imaging (MRI) imaging of WM progression, a sample size in the range of about 100 subjects per group could determine if RIC has activity in WM disease and VCI.

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The cerebral microvessels are parenchymal branches of the brain's penetrating vessels that include small diameter arterioles and capillaries and through which the cerebral microcirculation delivers vital metabolites to the brain. In contrast to conductance or meningeal vessels, vasomotor tone in cerebral microvessels is not dependent on the action of the sympathetic nervous system but rather on a combination of vasoreactive agents such as angiotensin, vasopressin, and purines from both brain endogenous and exogenous sources. The microvascular wall consists mainly of endothelial cells (ECs), smooth muscle cells, and pericytes (PCs) as well as the sieve-like basal lamina (BL), which together with perivascular astroglia (AS) interact dynamically to maintain the integrity and permeability of the blood-brain barrier (BBB). To ensure constant delivery of oxygen and glucose, the flow of blood through microcirculation is under autoregulatory control, both systemically and locally at the level of the microvascular wall. At the microvascular wall, endothelin (ET) and nitric oxide (NO) as well as circulating agents provide local vasopressor and vasodepressor effects that are crucial to maintain a normal vasomotor tone. Following trauma or stroke, three major pathologies occur: 1) alterations in structural integrity of microvessels and brain parenchymal cells, 2) acute edema formation, and 3) sustained hypoperfusion from vasospasm. Other pathologies that may contribute to a defective microcirculation include the formation of microthrombi and hemorrhaging, which can exacerbate the immune response. A defective microcirculation due to the loss of autoregulatory control of microvessels may contribute to the brain's shift to anaerobic metabolism and to the formation of oxygen-free radicals, considered to be a major source of injury to nerve cells and the BBB. The diverse pathophysiologies ensuing from these events lead to nerve cell loss and poor neurological outcome. Because of these diverse pathophysiologies, monotherapeutic interventions to improve the microcirculation after trauma and stroke have had limited success both at the bench and the clinic. Recent polytherapeutic interventions aiming at improving the microcirculation as well as cell viability and neurological outcome after trauma and stroke are discussed.

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Barbiturates are indicated for use during vascular neurosurgery procedures such as carotid surgery, arteriovenous malformation (AVM) surgery, cerebral aneurysm surgery, extracranial-intracranial bypass, and following significant bleeding due to AVMs or subarachnoid hemorrhage (SAH). These drugs are commonly used for their neuroprotective effects during focal cerebral ischemia and for their ability to treat intractable intracranial hypertension. Currently, thiopental and pentobarbital are the most frequently used barbiturates for these purposes, although methohexital and phenobarbital have been studied as well. Depending on the drug used and the desired effect, the dose administered may vary. Additionally, barbiturates are known to cause significant, severe side effects including depression of cardiac output, increased liver enzymes, increased risk of cardiac arrhythmia, lowered immune threshold, adversely affected brain temperature, systemic hypotension, and dyskalemia. For these reasons, these drugs should be monitored carefully and only used in circumstances of clear benefit. Finally, in order to evaluate barbiturates use during these procedures, information was gathered via an extensive PubMed literature review in addition to reviewing the resources of previous reviews on this topic or similar, relevant topics.

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This review examines stem cells harvested from human amniotic fluid and considers their possible applications in regenerative medicine, specifically for stroke therapy. Providing an early-stage, highly differentiable source of mesenchymal stem cells, amniotic fluid shows the potential to be effective in the development of future stem cell-based transplantation. This paper underscores the importance of pursuing amniotic fluid as a stem cell source in stroke therapy, citing both the characteristics and the demonstrated functional benefits of these cells in animal models. Additional research is required to discover the full range of amniotic fluid-derived stem cells' (AFSCs) applications but these cells have thus far demonstrated the ability to be applied to a wide array of existing and future treatment methods. Both amniotic fluid- and amnion membrane-derived stem cells (AMSCs) have their merits, and this assessment will accordingly provide a comparison of the benefits and drawbacks of both cell sources.

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The efficacy of stem cell therapy is greatly influenced by their secretory properties. Evidence suggests that there is a high concentration of growth factors such as brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and glial cell line-derived neurotrophic factor (GDNF) after stem cell transplantation. Also, the presence of therapeutic molecules and cytokines such as stem cell factor (SCF), stromal cell-derived factor-1α (SDF-1α), RNAs, nuclear enriched abundant transcript 1 (NEAT1), and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is consistent throughout several studies. Apart from modulating the homeostasis of the surrounding tissues, these factors have pleiotropic properties over the host tissue, among which are angiogenic, anti-inflammatory, antiapoptotic, and neurogenic effects. In the present manuscript, we discuss the different secretion factors and their beneficial activity after stem cell transplantation. Recent developments in emerging technologies for coadjunctive therapies that may aid in stem cell transplantation into the central nervous system, such as cell encapsulation, molecular Trojan horses, and viral vectors, are also presented in this article.

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Background: Remote ischemic preconditioning (PreC) and postconditioning (PostC) have all been shown to be neuroprotective against ischemia/reperfusion (I/R) injury. However, the underlying mechanisms of ischemic perconditioning (PerC) remain largely unknown. This study aimed to investigate the potential role of neural transmission pathways in the transference of protective signals evoked by PerC. Materials and Methods: Male Sprague-Dawley rats were randomly allocated into 12 groups [sham, middle cerebral artery occlusion (MCAO), MCAO+PerC, MCAO+PerC+vehicle, MCAO+PerC+Capsaicin, MCAO+PerC+sham, MCAO+PerC+denervation, MCAO+PostC, MCAO+PostC+vehicle, MCAO+PostC+sham, MCAO+PostC+Capsaicin, MCAO+PerC+denervation]. The I/R model was established by 90-min occlusion of the right middle cerebral artery and subsequent 24 h reperfusion. Remote conditioning was induced with three cycles of 10 min ischemia/10 min reperfusion of the femoral arteries bilaterally. Nerve block was conducted by local capsaicin treatment of exposed nerves or femoral and sciatic nerve transection. Cerebral infarct volumes were quantified by 2, 3, 4-triphenytetrazolium-chloride stain assay. The phosphorylation of Akt was detected by Western blot. Results: Remote ischemic PerC and PostC therapies reduced the infarct size and attenuated neurological deficits. Blocking the neural transmission pathways abolished the protective effect of PostC but had no effect on PerC. Further, blocking the neural transmission pathways reduced periinfarct Akt activation of PostC but had no effect on PerC. Conclusion: Unlike PostC, neural transmission pathways may not play a significant role in the transference of PerC-induced neuroprotection after I/R injury.

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