From Recognition to Remedy: The Significance of Biomarkers in Neurodegenerative Disease Pathology.

With the inexorable aging of the global populace, neurodegenerative diseases (NDs) like Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) pose escalating challenges, which are underscored by their socioeconomic repercussions. A pivotal aspect in addressing these challenges lies in the elucidation and application of biomarkers for timely diagnosis, vigilant monitoring, and effective treatment modalities. This review delineates the quintessence of biomarkers in the realm of NDs, elucidating various classifications and their indispensable roles. Particularly, the quest for novel biomarkers in AD, transcending traditional markers in PD, and the frontier of biomarker research in ALS are scrutinized. Emergent susceptibility and trait markers herald a new era of personalized medicine, promising enhanced treatment initiation especially in cases of SOD1-ALS. The discourse extends to diagnostic and state markers, revolutionizing early detection and monitoring, alongside progression markers that unveil the trajectory of NDs, propelling forward the potential for tailored interventions. The synergy between burgeoning technologies and innovative techniques like -omics, histologic assessments, and imaging is spotlighted, underscoring their pivotal roles in biomarker discovery. Reflecting on the progress hitherto, the review underscores the exigent need for multidisciplinary collaborations to surmount the challenges ahead, accelerate biomarker discovery, and herald a new epoch of understanding and managing NDs. Through a panoramic lens, this article endeavors to provide a comprehensive insight into the burgeoning field of biomarkers in NDs, spotlighting the promise they hold in transforming the diagnostic landscape, enhancing disease management, and illuminating the pathway toward efficacious therapeutic interventions.

Brain-heart axis--Review Article.

UNLABELLED: There has been a large confirmation over the last decades that stroke may produce cardiac changes (echocardiographic, electrocardiographic, enzymatic). In ischemic stroke, systolic dysfunction is associated with a high risk of mortality during hospitalization. A recent study demonstrated that cardiac diastolic dysfunction could also accompany acute stroke besides the systolic dysfunction already pointed out by previous studies, being a predictive marker of acute cerebrovascular events. Increased sympathetic activity is contributory, inducing a reversible cardiac myocyte damage and cardiac enzyme surges. Some of the most frequent electrocardiographic abnormalities in stroke are ST segment abnormalities and various tachyarrhythmias (especially atrial fibrillation) and bradyarrhythmias. One can infer the importance of careful and continuous electrocardiographic monitoring of the stroke patient in order to identify these quite frequent electrocardiographic alterations, as it is well known that death due to cardiac arrhythmias is common among acute stroke patients. In order to increase the diagnostic yield, a high level of NTproBNP (N-terminal of the prohormone brain natriuretic peptide) may be used as a discriminant for the patients with a higher probability of cardiac arrhythmias and mortality at presentation, during hospitalization and on the long term. In such patients, cardiac monitoring techniques are more likely to reveal abnormalities. A high BNP level may have potentially important management implications as it may signal a worse prognosis and may prompt the undertaking of certain therapeutic measures. This review summarizes the possible pathological mechanisms of heart-brain connections and their clinical and therapeutical implications. ABBREVIATIONS: AF = atrial fibrillation, ECG = electrocardiography, HRV = heart rate variability, cTn = cardiac troponin, SAH = subarachnoid hemorrhage, CK-MB = creatine kinase-MB, BNP = brain natriuretic peptide, NT-proBNP = N-terminal of the prohormone brain natriuretic peptide, ANP = atrial natriuretic peptide, mRS = modified Rankin Scale, NIHSS = the National Institutes of Health Stroke Scale.

Molecular basis of vascular events following spinal cord injury.

The aim of this article is to analyze the effects of the molecular basis of vascular events following spinal cord injury and their contribution in pathogenesis. First of all, we reviewed the anatomy of spinal cord vessels. The pathophysiology of spinal cord injuries revealed two types of pathogenic mechanisms. The primary event, the mechanic trauma, results in a disruption of neural and vascular structures into the spinal cord. It is followed by secondary pathogenesis that leads to the progression of the initial lesion. We reviewed vascular responses following spinal cord injury, focusing on both primary and secondary events. The intraparenchymal hemorrhage is a direct consequence of trauma; it has a typical pattem of distribution into the contused spinal cord, inside the gray matter and, it is radially extended into the white matter. The intraparenchymal hemorrhage is restricted to the dorsal columns, into adjacent rostral and caudal spinal segments. Distribution of chronic lesions overlaps the pattern of the early intraparenchymal hemorrhage. We described the mechanisms of action, role, induction and distribution of the heme oxygenase isoenzymes 1 and 2. Posttraumatic inflammatory response contributes to secondary pathogenesis. We analyzed the types of cells participating in the inflammatory response, the moment of appearance after the injury, the decrease in number, and the nature of their actions. The disruption of the blood-spinal cord barrier is biphasic. It exposes the spinal cord to inflammatory cells and to toxic effects of other molecules. Endothelin 1 mediates oxidative stress into the spinal cord through the modulation of spinal cord blood flow. The role of matrix metalloproteinases in blood-spinal cord barrier disruption, inflammation, and angiogenesis are reviewed.

Vascular dysfunctions following spinal cord injury.

The aim of this article is to analyze the vascular dysfunctions occurring after spinal cord injury (SCI). Vascular dysfunctions are common complications of SCI. Cardiovascular disturbances are the leading causes of morbidity and mortality in both acute and chronic stages of SCI. Neuroanatomy and physiology of autonomic nervous system, sympathetic and parasympathetic, is reviewed. SCI implies disruption of descendent pathways from central centers to spinal sympathetic neurons, originating in intermediolateral nuclei of T1-L2 cord segments. Loss of supraspinal control over sympathetic nervous system results in reduced overall sympathetic activity below the level of injury and unopposed parasympathetic outflow through intact vagal nerve. SCI associates significant vascular dysfunction. Spinal shock occurs during the acute phase following SCI and it is a transitory suspension of function and reflexes below the level of the injury. Neurogenic shock, part of spinal shock, consists of severe arterial hypotension and bradycardia. Autonomic dysreflexia appears during the chronic phase, after spinal shock resolution, and it is a life-threatening syndrome of massive imbalanced reflex sympathetic discharge occurring in patients with SCI above the splanchnic sympathetic outflow (T5-T6). Arterial hypotension with orthostatic hypotension occurs in both acute and chronic phases. The etiology is multifactorial. We described a few factors influencing the orthostatic hypotension occurrence in SCI: sympathetic nervous system dysfunction, low plasma catecholamine levels, rennin-angiotensin-aldosterone activity, peripheral alpha-adrenoceptor hyperresponsiveness, impaired function of baroreceptors, hyponatremia and low plasmatic volume, cardiovascular deconditioning, morphologic changes in sympathetic neurons, plasticity within spinal circuits, and motor deficit leading to loss of skeletal muscle pumping activity. Additional associated cardiovascular concerns in SCI, such as deep vein thrombosis and long-term risk for coronary heart disease and systemic atherosclerosis are also described. Proper prophylaxis, including non-pharmacologic and pharmacological strategies, diminishes the occurrence of the vascular dysfunction following SCI. Each vascular disturbance requires a specific treatment.

Deficiencies of proteins C, S and antithrombin and factor V Leiden and the risk of ischemic strokes.

Although hypercoagulable states are most often associated with venous thromboses, arterial thromboses are reported in protein C, protein S, antithrombin deficient patients and in those with factor V Leiden, components of hereditary thrombophilia. Because these arterial thromboses (peripheral artery disease, myocardial infarction, and cerebral infarction) mostly affect young persons, aged below 45 years, it is important to test and treat these thrombophilic defects. Because the relation thrombophilia--arterial thromboses is still under debate, due to conflicting data, this article is a review of studies published in literature regarding the implication of the above-mentioned thrombophilic defects in cerebral infarcts.

Deficiencies of proteins C, S and antithrombin and activated protein C resistance--their involvement in the occurrence of Arterial thromboses.

Deficiencies of natural anticoagulants protein C, protein S, antithrombin and activated protein C resistance are components of inherited thrombophilia. Inherited thrombophilia was defined as a genetically determined tendency towards venous thromboembolism, which characteristically occurs in young patients (before 40 to 45 years old), without apparent causes, and tend to recur. There have been many debates about the implication of these defects in arterial thromboses (peripheral artery disease, myocardial infarction, cerebral infarction) in the recent years. The screening for thrombophilia is recommended for young patients with spontaneous thromboses, arterial infarctions, family history of thromboses, personal history of recurrent abortions, with thrombosis of venous dural sinuses or strokes or myocardial infarctions, in patients with venous thrombosis in unusual sites, because the diagnosis of such a disease leads to a treatment that is lifesaving [1,2].