Acute brain injuries, including ischemic and hemorrhagic stroke, as well as traumatic brain injury (TBI), are major worldwide health concerns with very limited options for effective diagnosis and treatment. Stroke and TBI pose an increased risk for the development of chronic neurodegenerative diseases, notably chronic traumatic encephalopathy, Alzheimer's disease, and Parkinson's disease. The existence of premorbid neurodegenerative diseases can exacerbate the severity and prognosis of acute brain injuries. Apoptosis involving caspase-3 is one of the most common mechanisms involved in the etiopathology of both acute and chronic neurological and neurodegenerative diseases, suggesting a relationship between these disorders. Over the past two decades, several clinical biomarkers of apoptosis have been identified in cerebrospinal fluid and peripheral blood following ischemic stroke, intracerebral and subarachnoid hemorrhage, and TBI. These biomarkers include selected caspases, notably caspase-3 and its specific cleavage products such as caspase-cleaved cytokeratin-18, caspase-cleaved tau, and a caspase-specific 120 kDa αII-spectrin breakdown product. The levels of these biomarkers might be a valuable tool for the identification of pathological pathways such as apoptosis and inflammation involved in injury progression, assessment of injury severity, and prediction of clinical outcomes. This review focuses on clinical studies involving biomarkers of caspase-3-mediated pathways, following stroke and TBI. The review further examines their prospective diagnostic utility, as well as clinical utility for improved personalized treatment of stroke and TBI patients and the development of prophylactic treatment chronic neurodegenerative disease.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

In this paper, our review series on cerebrovascular disease anatomy, physiology, and pathology ends with a thorough discussion of the most significant cerebrovascular pathology: stroke. This discussion proceeds through two layers of organization. First, stroke is divided up into its main etiologic categories (ischemic stroke/transient ischemic attack, hemorrhagic stroke, and ischemic to hemorrhagic transformation). Then, the epidemiological, pathophysiological, clinical, and therapeutic (employed currently as well as emerging) aspects of each etiology are explored; emphasis is placed upon the therapeutic aspects. Finally, once we have covered all aspects of each etiologic category, we end our review with a defense of the thesis that there is much hope for the future of stroke treatment to be derived from familiarity with the literature on emerging therapies.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

In this paper, which is the first in a three-part series that reviews cerebrovascular anatomy, pathogenesis, and stroke, we lay the anatomical foundation for the rest of the series. Beginning with its origin in the branches of the aorta, we start by describing the arterial system. This system is partitioned into two major divisions (anterior and posterior circulations) that differ significantly in features and pathogenic potential. The systems, and the major branches that comprise them, are described. Description of the arterial system proceeds to the point of the fulfillment of its function. This function, the exchange of gases and nutrients with the cerebral parenchyma, is the subject of a subsequent section on the microcirculation and blood–brain barrier. Finally, the cerebral venous system, which is composed of cerebral veins and dural venous sinuses, is described. Thus, an anatomical context is supplied for the discussion of cerebrovascular disease pathogenesis provided by our second paper.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

In this paper, we review the cerebral circulation and cerebrovascular disease (CVD) with an overview of the major types of CVD pathogenesis. These, as categorized here, are as follows: occlusive injury intrinsic to blood vessels, occlusive injury extrinsic to blood vessels, cerebral hypoperfusion, and cerebral hemorrhage. Following an overview of each of these categories, we conclude with a discussion of cerebral edema to illustrate how the pathological origins we covered can progress clinically. The content of this paper sets the stage for the detailed, clinically oriented discussion of stroke with which our series culminates in its subsequent Part III.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Brief periods of ischemia have been shown in many experimental setups to provide tolerance against ischemia in multiple organs including the brain, when administered before (preconditioning) or even after (postconditioning) the normally lethal ischemia. In addition to these so-called ischemic conditionings, many pharmacological and natural agents (e.g., chemicals and nutraceuticals) can also act as potent pre- and post-conditioners. Deriving from the original concept of ischemic preconditioning, these various conditioning paradigms may be promising as clinical-stage therapies for prevention of ischemic-related injury, especially stroke. As no proven experimentally identified strategy has translated into clinical success, the experimental induction of neuroprotection using these various conditioning paradigms has raised several questions, even before considering translation to clinical studies in humans. The first aim of the review is to consider key questions on preclinical studies of pre- or post-conditioning modalities including those induced by chemical or nutraceuticals. Second, we make the argument that several key issues can be addressed by a novel concept, nutraceutical preconditioning. Specifically, α-linolenic acid (alpha-linolenic acid [ALA] an omega-3 polyunsaturated fatty acid), contained in plant-derived edible products, is essential in the daily diet, and a body of work has identified ALA as a pre- and post-conditioner of the brain. Nutritional intervention and functional food development are an emerging direction for preventing stroke damage, offering the potential to improving clinical outcomes through activation of the endogenous protective mechanisms known collectively as conditioning.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage. Great progress has been made in understanding the important roles of various G protein-coupled receptors in the regulation of pain transmission. However, many important questions remain uncertain about the precise signal transduction mechanisms. This review focuses opioid receptor and CXC receptor 4 on the effects and mechanisms of pain. Taken together, chemokines and their receptors are potential targets for the development of novel pain management and therapy.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

BACKGROUND: Hypertension, diabetes, and smoking were considered to be associated with several public health problems. OBJECTIVE: the study aims to explore the hemodynamic of carotid arteries in association with hypertension, diabetes, and smoking in Sudanese stroke patients. MATERIALS AND METHODS: In a quantitative descriptive study, fifty patients with stroke were scanned by B-mode and Doppler sonography. Carotid arteries were investigated with a 7-MHz linear transducer by a standard carotid sonography protocol. RESULTS: The average Doppler resistive index (RI) was 0.71 ± 0.084 and intima-media thickness was 1.39 ± 0.78 mm. The end diastolic velocities (EDVs) and peak systolic velocities (PSVs) of common carotid arteries were significantly changed in smokers and hypertensive (P < 0.05). The elevation of RI in right and left CCAs were significantly correlated with smokers (P = 0.017 and 0.010 respectively). Hemorrhagic stroke was most prevalent in hypertensive rather than diabetic and smokers. The carotid hemodynamics changed significantly in hypertensive and smokers more than diabetics. CONCLUSION: EDV and PSV were significantly correlated with hypertension and tobacco smoking rather than diabetes. Hypertension, diabetes, and smoking have an association with stroke and hand significant effect on carotid artery hemodynamic and atherosclerotic disease. The Doppler RIs were significantly correlated with smokers. Patients with risk factors of stroke should be scanned with Doppler sonography as early as possible.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

[FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]