Therapeutic Design in Vascular Disorders in Brain CNS Disease

Therapeutic Design Vascular Disorder

Research on the design of effective therapies for CNS disease has focused primarily on neurons, which is referred to as the eurocentric view. Although placing great emphasis on neurons has provided in-depth knowledge of the disruption of their cell biology during chronic neuro-degenerative situations, it fails to address the underlying disease pathology and, as a consequence, this strategy does not lead to disease-modifying therapy.

The explanation is that non-neuronal cells are also involved in the complex pathogenesis of CNS diseases and play a key role in neurodegenerative processes.

This fact is still an exacerbating factor in neurodegenerative diseases in which chronic cerebral hypoperfusion is added to the decline in cerebral blood flow associated with aging.

Acute Event

Among stroke cases, 80% consist of ischemic stroke, hemorrhagic stroke is responsible for 15% and 5% is of unknown cause (Beal, 2010). It is especially of concern that epidemiological studies report an increasing incidence and proportion of young adult patients with stroke (Ekker et al., 2018).

Control of hypertension, together with moderate or low salt intake, is a major determinant of long-term reduction in mortality from cerebrovascular disease (hemorrhagic and ischemic stroke) (Levi et al., 2009; Petersen et al., 2019).

Neurodegenerative Disease

Chronic brain hypoperfusion is present in AD, ALS, VP, VaD, and aging, and may precede the appearance of clinical symptoms or neurodegenerative signs, so it is highly probable that the pathogenesis of this neurodegenerative disease may depend on its formation. vascular pathology and/or loss of van micro-cultures (de la Torre, 2017).

1. Alzheimer's disease. AD is the most common cause of dementia. The greatest risk factors for late-onset Alzheimer's are older age, up to 65 years, (Hebert et al., 2010), genetics (Farrer et al., 1997), and having a family history of Alzheimer's (Green et al., 2002; Lautenschlager et al., 1996; Mayeux et al., 1991).

2. Amyotrophic Lateral Sclerosis. ALS is a neurodegenerative disorder characterized by progressive degeneration of motor neurons in the brain and spinal cord, leading to muscle atrophy, paralysis, and premature death from diagnosis (Haverkamp et al., 1995; Rowland and Shneider, 2001).

3. Vascular Parkinsonism. Vascular changes in the brain are the hallmark of VP (Korczyn, 2015), which accounts for 3-5% of all patients with parkinsonism (Jellinger, 2003). Although the precise changes in blood vessels have not been described in detail, these changes are usually ischemic and affect brain areas relevant to parkinsonism, including the subcortical white matter, basal ganglia, thalamus, and upper brainstem (Foltynie et al., 2002).

4. Vascular dementia. As stated in the National Institute on Aging (http://www.nia.nih.gov/health/vascular-contributions-cognitive-impairment-and-dementia ), it is called cerebrovascular disease when there is damage or microvascular pathology of the brain—also known as cerebrovascular disease. small blood vessels—causing brain tissue injury—due to decreased blood flow, oxygen, or nutrients—contributing to cognitive impairment and dementia (Roman, 2004).

5. Aging. Aging is a major risk factor for most neurodegenerative diseases, the prevalence of which increases with age (Hou et al., 2019). This fact can be directly or indirectly related to endothelial dysfunction (Bersini et al., 2020; Ungvari et al., 2013; Ungvari et al., 2020), decreased cerebral blood flow, approximately 20% decrease in flow, (Leenders et al., 1990; Zou et al., 2009) and BBB leakage (Verheggen et al., 2020) that occur with aging. In addition, there is scientific consensus on the important role of microvascular contributions to cognitive impairment in elderly patients (Tarantini et al., 2017).

Source

Gallego, I., Villate-Beitia, I., Saenz-del-Burgo, L., Puras, G., & Pedraz, J. L. (2022). Therapeutic Opportunities and Delivery Strategies for Brain Revascularization in Stroke, Neurodegeneration, and Aging. Pharmacological Reviews, 74(2), 439-461.

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1 Response to "Therapeutic Design in Vascular Disorders in Brain CNS Disease"

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