Parenchymal volume loss in the brain refers to the reduction in the amount of functional brain tissue, including neurons and supporting cells, which leads to brain shrinkage or atrophy. This phenomenon can occur due to a variety of causes, often involving complex pathological processes that damage brain cells or disrupt their normal function.
One of the primary causes of parenchymal volume loss is **neurodegenerative diseases**, with Alzheimer’s disease being the most common example. In Alzheimer’s, abnormal protein deposits such as amyloid-beta plaques and neurofibrillary tangles accumulate in the brain, triggering chronic inflammation and progressive neuronal death. This leads to a gradual loss of brain tissue, especially in areas like the neocortex, limbic system, and hippocampus, which are critical for memory and cognition. The inflammation activates microglial cells, which release harmful substances that further damage neurons, accelerating brain atrophy[4][5].
Another significant cause is **vascular pathology**, including conditions that impair blood flow to the brain. Chronic hypertension, small vessel disease, and cerebral amyloid angiopathy (CAA) can lead to microvascular obstruction and ischemia (lack of oxygen), damaging brain tissue. This damage can cause white matter lesions and contribute to parenchymal loss. In CAA, amyloid deposits in the walls of blood vessels can deform them, leading to mechanical stress and impaired blood flow, which in turn causes brain tissue shrinkage[1][5].
**Hypoxic-ischemic injury**, especially in premature infants, is a well-known cause of parenchymal volume loss. For example, periventricular leukomalacia (PVL) is a type of white matter injury that occurs due to insufficient blood supply and oxygen to the periventricular regions of the brain. This leads to necrosis (cell death) of white matter, cyst formation, and eventual loss of brain tissue volume. PVL is often associated with cerebral palsy and intellectual disabilities in affected children[3].
**Inflammation and infection** can also cause brain tissue loss. Chronic inflammation, whether from autoimmune diseases, infections, or other causes, can damage neurons and glial cells. Infections such as encephalitis or meningitis may cause direct injury to brain tissue or trigger immune responses that result in parenchymal loss.
**Traumatic brain injury (TBI)** is another important cause. Severe or repeated head trauma can damage neurons and supporting structures, leading to localized or diffuse brain atrophy over time. The injury may disrupt blood flow, cause inflammation, and trigger cell death pathways.
**Metabolic and toxic causes** also contribute to parenchymal volume loss. Deficiencies in essential nutrients (like vitamin B12), chronic alcohol abuse, exposure to toxins, or certain metabolic disorders can impair neuronal health and survival, resulting in brain shrinkage.
**Genetic and developmental disorders** may cause brain volume loss either prenatally or during early life. Some inherited conditions affect the formation, maintenance, or survival of brain cells, leading to progressive atrophy.
In some cases, **encephalomalacia**, which is the softening or loss of brain tissue following injury such as stroke or infection, results in localized parenchymal volume loss. This can be seen as cystic areas where brain tissue has been destroyed and replaced by fluid[2].
The mechanisms behind parenchymal volume loss often involve a combination of:
– **Neuronal death**: Loss of neurons due to toxic proteins, ischemia, inflammation, or trauma.
– **Glial cell dysfunction**: Supporting cells like oligodendrocytes and astrocytes may fail to maintain neuronal health or myelination.
– **Vascular insufficiency**: Reduced blood flow deprives brain tissue of oxygen and nutrients.
– **Inflammatory responses**: Chronic activation of immune cells in the brain causes secondary damage.
– **Mechanical factors**: Changes in blood vessel structur
